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Biomedical subjects

L Yeung

Publications and source records attributed to L Yeung.

13 recordsLinked to original sources
PubMed2001

Human herpesvirus 6 reactivation and encephalitis in allogeneic bone marrow transplant recipients.

To determine whether receipt of an investigational anti-CD3 monoclonal antibody (BC3) increased the risk of human herpesvirus 6 (HHV-6) reactivation and development of encephalitis in bone marrow transplant (BMT) recipients, persons who had and had not received BC3 were compared. Odds of HHV-6 reactivation were higher among BC3 recipients than among control patients (odds ratio, 2.5; 95% confidence interval [CI], 1.3-4.7). In addition, BC3 recipients were more likely than control patients to develop encephalitis (risk ratio [RR], 3.5; 95% CI, 1.3-9.5), and this association followed a BC3 dose-dependent relationship (P=.03, by Mantel-Haenszel chi(2) test). In a multivariable model, HHV-6 reactivation and receipt of BC3 were associated with increased risk of encephalitis (RR, 5.4; 95% CI, 1.9-15.3, and RR, 3.3; 95% CI, 1.2-9.1, respectively). In conclusion, both HHV-6 reactivation and receipt of BC3 for prophylaxis of acute graft-versus-host disease independently increased the risk of encephalitis in allogeneic BMT recipients. Prospective studies to better define the relationship between HHV-6 reactivation and encephalitis in allogeneic BMT recipients are warranted.

Adult↗
PubMed2001

Multiple founder effects in spinal and bulbar muscular atrophy (SBMA, Kennedy disease) around the world.

SBMA (spinal and bulbar muscular atrophy), also called Kennedy disease, is an X-chromosomal recessive adult-onset neurodegenerative disorder caused by death of the spinal and bulbar motor neurones and dorsal root ganglia. Patients may also show signs of partial androgen insensitivity. SBMA is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene on the X-chromosome. Our previous study suggested that all the Nordic patients with SBMA originated from an ancient Nordic founder mutation, but the new intragenic SNP marker ARd12 revealed that the Danish patients derive their disease chromosome from another ancestor. In search of relationships between patients from different countries, we haplotyped altogether 123 SBMA families from different parts of the world for two intragenic markers and 16 microsatellites spanning 25 cM around the AR gene. The fact that different SBMA founder haplotypes were found in patients from around the world implies that the CAG repeat expansion mutation has not been a unique event. No expansion-prone haplotype could be detected. Trinucleotide diseases often show correlation between the repeat length and the severity and earlier onset of the disease. The longer the repeat, the more severe the symptoms are and the onset of the disease is earlier. A negative correlation between the CAG repeat length and the age of onset was found in the 95 SBMA patients with defined ages at onset.

Exons↗
PubMed2001

Effects of dopamine antagonists in human eye accommodation.

The purpose of this study was to evaluate the effects of dopamine antagonists in accommodation of the human eye. The dopamine antagonist drugs used in this experiment include 0.5% metoclopramide and 0.25% droperidol. Eighteen healthy subjects were enrolled; they were randomly assigned, in double-masked fashion, to receive topical administration of a single drop of either 0.5% metoclopramide or 0.25% droperidol in one eye, with the fellow eye receiving isotonic saline as control. The accommodative abilities of both eyes were measured before instillation, and also at 3 and 6 hr after instillation of drugs, respectively. We studied the latency of reaction, the rate of accommodation, the average accommodative power, the rate of recovering and the total recovering time as the five parameters for evaluating the accommodative ability of each eye. The results showed that there were significant changes in two parameters: the rate of accommodation and rate of recovering, whereas there were no significant changes in the other three parameters: latency of accommodation, average power of accommodation and total recovering time. In conclusion, the dopamine antagonists may have some effects on the rate of accommodation but not the degree of accommodation. Further studies with higher concentrations of these dopamine antagonists on dose-response relationships are needed before exact drug efficacy can be drawn.

Accommodation, Ocular↗
PubMed2001

Anti-ischemic action of estrogen-progestogen continuous combined hormone replacement therapy in postmenopausal women with established angina pectoris: a randomized, placebo-controlled, double-blind, parallel-group trial.

The benefit of treating postmenopausal women with established cardiovascular disease with combined estrogen-progestogen hormone replacement therapy (HRT) is controversial. This study investigated the effect of treatment with estradiol and norethisterone acetate on exercise tolerance and on the frequency and severity of ischemic attacks in postmenopausal women with stable angina pectoris. A total of 74 Chinese women were recruited for this 16-week double-blind, placebo-controlled trial. They were randomly allocated into two groups; one group received placebo/placebo/placebo and the other group received placebo/estrogen-progestogen/placebo. Estrogen-progestogen continuous combined HRT increased both time to 1-mm ST depression (99.1 s, p < 0.05) compared with a mean decrease of 22.9 s with placebo (p < 0.05), and total exercise duration also showed a significant increase (32.7 s, p < 0.05) after treatment compared with placebo (2.5 s, p < 0.05). In addition, the total number of ischemic events/24 h during ambulatory electrocardiographic monitoring decreased by 0.82 events after treatment (p < 0.05) compared with an increase in the placebo group (0.94), a highly significant difference (p = 0.006). These results suggest that the administration of this particular combined hormone replacement preparation may have a beneficial effect on myocardial ischemia in postmenopausal women with established coronary disease.

Aged↗
PubMed1998

The correlation of clinical phenotype in Friedreich ataxia with the site of point mutations in the FRDA gene.

Most cases of Friedreich ataxia (FRDA) are due to expansions of a GAA trinucleotide repeat sequence in the FRDA gene coding for frataxin, a protein of poorly understood function which may regulate mitochondrial iron transport. However, between 1% and 5% of mutations are single base changes in the sequence of the FRDA gene, causing missense, nonsense, or splicing mutations. We describe three new mutations, IVS4nt2 (T to G), R165C, and L182F, which occur in patients in association with GAA expansions. These cases, and a further five reported cases of point mutations causing FRDA, demonstrate that splicing, nonsense, or initiation codon mutations (which cause a complete absence of functional frataxin) are associated with a severe phenotype. Missense mutations, even in highly evolutionally conserved amino acids, may cause a mild or severe phenotype.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Efficient neurophysiologic selection of X-linked Charcot-Marie-Tooth families: ten novel mutations.

OBJECTIVE: To devise a neurophysiologic strategy to select X-linked Charcot-Marie-Tooth neuropathy syndrome (CMTX) families for connexin 32 mutation screening. BACKGROUND: Once the common chromosome 17 DNA duplication (CMT1A syndrome) has been excluded, clinical features are not sufficiently distinctive to select which of three genes (PMP22, Po, or connexin 32) should be screened for mutations. DESIGN: The yield of connexin 32 mutations was compared in possible CMTX families with clinical and genetic features of CMTX and probable CMTX families, defined by additional characteristic neurophysiologic features of CMTX. Of 232 CMT families with median motor nerve conduction velocities below 50 m/second (s) in affected men, 50 were found to have no CMT1A duplication and a pattern of inheritance compatible with CMTX (no man-to-man inheritance of CMT). These families were divided into 23 probable CMTX families (defined as having electrophysiologic indicators of CMTX), 23 possible CMTX families (with no neurophysiologic features of CMTX), and five unlikely CMTX families (with normal brainstem evoked auditory potentials [BAEPs]). RESULTS: The yield of mutations in the whole group was 25 mutations in 51 families (50%). Most probable CMTX families (21 of 23; 91%) had connexin 32 coding region mutations. Included in this group were 14 families with obligate female carriers; 11 of these had intermediate conduction velocities (>42 m/s) and nine (81%) had connexin 32 mutations. Only 3 of 23 (13%) possible CMTX families had connexin 32 mutations. One of five families with normal BAEPs in affected men had a connexin 32 mutation, and one had a Po Ala112Val mutation. Seventeen different mutations were found among 24 families, including 10 previously undescribed mutations (Leu9Trp, Ile28Thr, Ile30Thr, Ile127Met, Leu131Pro, Tyr154 stop, Pro158Ala, one base deletion of codon 158 causing stop at codon 195, Val192Phe, and Leu239Ile). CONCLUSIONS: The yield of connexin 32 mutations can be increased from approximately 6% of all CMT type I families to 91% of nonduplicated nondominant families with characteristic electrophysiologic changes of CMTX.

Amino Acid Substitution↗
PubMed1996

Right ventricular diastolic dysfunction in heart failure.

BACKGROUND: Left ventricular (LV) diastolic dysfunction is common in heart failure and is an important predictor of prognosis and mortality. Less attention has been paid to right ventricular (RV) diastolic function. In this study, we compared RV diastolic function in a large cohort of patients with heart failure (HF) with two groups: patients with pulmonary hypertension and normal LV function (the PHT group) and normal subjects. METHODS AND RESULTS: Transtricuspid and pulmonary artery flow were assessed by two-dimensional Doppler echocardiography at maximum inspiration and expiration in 185 subjects: 114 symptomatic HF patients (ejection fraction < 0.5), 31 PHT patients (pulmonary artery systolic pressure > 40 mm Hg), and 40 normal subjects. A subset was matched for age and heart rate. The results showed a high prevalence of RV diastolic abnormalities: HF patients had lower tricuspid E-A ratios, lower peak E-wave velocity, and prolonged RV isovolumic relaxation time (all P< .0001). Tricuspid E-wave deceleration time was significantly shorter only in those who had an LV restrictive filling pattern. The PHT group had similar findings. Compared with a normal range, more than half of the patients had lower tricuspid E-A ratios (HF, 55%; PHT, 69%), and 61% of HF and 58% of PHT patients had a prolonged RV isovolumic relaxation time. In the PHT group, RV diastolic parameters (E-wave deceleration time, E-A ratio, and isovolumic relaxation time) correlated significantly with pulmonary artery systolic pressure (P< .05). In the HF group, however, only tricuspid E-wave deceleration time correlated significantly with pulmonary artery systolic pressure, and HF patients with normal pulmonary artery systolic pressures had significantly lower tricuspid E-A ratios and prolonged RV isovolumic relaxation times compared with normal subjects. A close correlation existed between individual RV and LV diastolic parameters, suggesting that LV diastolic dysfunction may directly affect RV function, but there was no relation between LV size or systolic function and RV diastolic dysfunction. CONCLUSIONS: RV diastolic function is frequently abnormal in HF patients, and this is not related to elevated pulmonary artery systolic pressure alone, although high pulmonary artery pressure by itself also is associated with impaired RV diastolic function. Assessment of the role of right ventricular diastolic function in determining the symptoms and prognosis of heart failure is warranted.

Diastole↗
PubMed1996

Ambulatory parathyroidectomy for primary hyperparathyroidism.

OBJECTIVE: To evaluate whether the combined application of preoperative localization and intraoperative monitoring of intact parathyroid hormone (iPTH) levels could facilitate safe outpatient parathyroidectomy. DESIGN: Consecutive patients, who had no antecedent social or medical conditions mandating hospitalization, were prospectively offered ambulatory parathyroidectomy with a mean follow-up of 7 months (range, 1-25 months). SETTING: Tertiary care referral center PATIENTS: From 85 patients who had primary hyperparathyroidism with hypercalcemia and elevated iPTH levels, 57 were offered outpatient parathyroidectomy. Nineteen patients were asymptomatic, 3 had hypercalcemic crisis, and the others gave a history of renal stones or had complaints consistent with bone disease. INTERVENTIONS: Technetium Tc 99m sestamibi scintiscans were used for preoperative localization. Monitoring iPTH levels during parathyroidectomy quantitatively assured the surgeon (G.L.I. only) when all hyperfunctioning glands were excised. MAIN OUTCOME MEASURE: The number of patients without complications and with short operative times who were discharged without hospital admission or overnight stay. RESULTS: The combination of preoperative localization of abnormal parathyroid glands and a decline in circulating iPTH levels predicting postoperative normocalcemia after excision of all hyperfunctioning glands resulted in successful parathyroidectomy in 84 of 85 patients. A decreased operative time (average, 52 minutes) with minimal neck dissection permitted outpatient parathyroidectomy in 42 of 57 eligible patients. CONCLUSIONS: The combination of preoperative parathyroid scintiscan localization and iPTH level monitoring during surgery permitted successful parathyroidectomy in an ambulatory setting in half of a consecutive series of patients with primary hyperparathyroidism. The safety, success, and likely cost savings of this approach suggest wider application.

Adolescent↗
PubMed1996

Three novel mutations and two variants in the gene for Cu/Zn superoxide dismutase in familial amyotrophic lateral sclerosis.

Autosomal dominant inheritance is exhibited by about 10% of cases of amyotrophic lateral sclerosis (ALS), a paralytic disorder characterized by the death of motor neurons in the brain and spinal cord. A subgroup of these familial cases are linked to mutations in the gene which codes for Cu/Zn superoxide dismutase (SOD1). We report three additional mutations occurring in the SOD1 gene in ALS patients and two single base pair variant changes. The single base pair change in an ALS family causes a glycine 93 to valine substitution, which is the fifth distinct amino acid change reported for the glycine 93 residue. One missense mutation in exon 5 would substitute neutral valine for the negatively-charged aspartate 124 (aspartate 124 to valine). An individual with an apparently sporadic case of ALS carries a three base pair deletion in exon 5 of the SOD1 gene. These three mutations bring to 38 the total number of distinct SOD1 mutations associated with familial ALS.

Amyotrophic Lateral Sclerosis↗
PubMed1994

Artifactual staining of monoclonal antibodies in two-color combinations is due to an immunoglobulin in the serum and plasma.

Two-color whole blood lysis is the assay of choice for lymphocyte immunophenotyping because of the additional information it provides. Recently, artifactual double-staining of some specimens has been observed with this assay. In these cases, the samples appear to be uncompensated for spectral overlap or to inappropriately coexpress two antigens simultaneously. This artifact can result in the apparent coexpression of CD4 and CD8 (observed in lymphoblastic processes) or of CD5 and CD20 (characteristic of chronic lymphocytic leukemia) in normal persons, leading to an erroneous diagnosis. Using plasma, serum, or immunoglobulin preparations from donors who exhibit this artifact we sought to determine 1) the source of the artifact and 2) ways to overcome it. This staining is apparently due to an immunoglobulin in the donors' serum and plasma which does not have specific reactivity with mouse immunoglobulin. Washing whole blood samples or blocking with mouse immunoglobulin is a convenient way of avoiding this artifact.

Antibodies, Monoclonal↗