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Biomedical subjects

A Y Lam

Publications and source records attributed to A Y Lam.

6 recordsLinked to original sources
PubMed2003

Dense linkage disequilibrium mapping in the 15q11-q13 maternal expression domain yields evidence for association in autism.

Autism [MIM 209850] is a neurodevelopmental disorder exhibiting a complex genetic etiology with clinical and locus heterogeneity. Chromosome 15q11-q13 has been proposed to harbor a gene for autism susceptibility based on (1) maternal-specific chromosomal duplications seen in autism and (2) positive evidence for linkage disequilibrium (LD) at 15q markers in chromosomally normal autism families. To investigate and localize a potential susceptibility variant, we developed a dense single nucleotide polymorphism (SNP) map of the maternal expression domain in proximal 15q. We analyzed 29 SNPs spanning the two known imprinted, maternally expressed genes in the interval (UBE3A and ATP10C) and putative imprinting control regions. With a marker coverage of 1/10 kb in coding regions and 1/15 kb in large 5' introns, this map was employed to thoroughly dissect LD in autism families. Two SNPs within ATP10C demonstrated evidence for preferential allelic transmission to affected offspring. The signal detected at these SNPs was stronger in singleton families, and an adjacent SNP demonstrated transmission distortion in this subset. All SNPs showing allelic association lie within islands of sequence homology between human and mouse genomes that may be part of an ancestral haplotype containing a functional susceptibility allele. The region was further explored for recombination hot spots and haplotype blocks to evaluate haplotype transmission. Five haplotype blocks were defined within this region. One haplotype within ATP10C displayed suggestive evidence for preferential transmission. Interpretation of these data will require replication across data sets, evaluation of potential functional effects of associated alleles, and a thorough assessment of haplotype transmission within ATP10C and neighboring genes. Nevertheless, these findings are consistent with the presence of an autism susceptibility locus in 15q11-q13.

Autistic Disorder↗
PubMed2001

A retrospective study on the efficacy and complications of Q-switched alexandrite laser in the treatment of acquired bilateral nevus of Ota-like macules.

BACKGROUND: Acquired bilateral nevus of Ota-like macules (ABNOM), or Hori's macules, is a common Asian condition that is characterized by bluish hyperpigmentation in the bilateral malar regions. Unlike nevus of Ota, ABNOM is an acquired condition that often develops after 20 years of age and involves both sides of the face, but there is no mucosal involvement. Recently Q-switched (QS) 1064 nm Nd:YAG lasers have been effective in clearing this condition. The effectiveness of QS alexandrite lasers has not yet been studied. OBJECTIVE: To retrospectively assess the efficacy and complications of QS alexandrite lasers in the treatment of ABNOM. METHODS: Thirty-two Chinese women with ABNOM ranging in age from 28 to 66 years were involved in the study. All underwent QS alexandrite laser treatment (755 nm, spot size 3 mm, 8 J/cm(2)). Topical hydroquinone and tretinoin cream were given to those with hyperpigmentation after the laser surgery. Clinical photographs were taken before and after laser surgery and assessed by two independent observers. The degree of clearing was scored and complications, including hypopigmentation, hyperpigmentation, scarring, and erythema, were assessed. RESULTS: The mean number of treatment sessions was 7 (range 2-11) and the mean treatment interval was 33 days. Both observers identified more than 80% of the patients as having more than a 50% degree of clearing, and complete clearance was seen in more than 28% of patients. Although most patients had postlaser hyperpigmentation and were on depigmentary regimes, the hyperpigmentation was seen in only 12.5% of the patients during photographic evaluation. Hypopigmentation was seen in 50% of patients and erythema in 41%. CONCLUSION: QS alexandrite appears to be effective in the treatment of ABNOM. Postoperative pigmentary changes were frequent and the use of topical depigmentary agents was necessary to achieve a satisfactory result. Transient hypopigmentation risk was high, affecting up to 50% of the patients. Further study is warranted to compare the efficacy and complications of different laser systems in the treatment of this condition.

Adult↗
PubMed2001

Possible interaction between warfarin and Lycium barbarum L.

OBJECTIVE: To describe a patient who was stabilized on warfarin and developed an elevated international normalized ratio (INR) after drinking a concentrated Chinese herbal tea. Additionally, to determine the effect of the tea on CYP2C9, the isoenzyme responsible for the metabolism of S-warfarin. CASE SUMMARY: An elevated INR of 4.1 was observed in a 61-year-old Chinese woman, previously stabilized on anticoagulation therapy (INR 2-3). With no changes in her other medications or lifestyle, a review of her dietary habits revealed four days of drinking a concentrated Chinese herbal tea made from Lycium barbarum L. fruits (3-4 glasses daily) prior to her clinic visit Warfarin was withheld for one day and then resumed at a lower weekly dose. She discontinued the tea, while maintaining consistency with medications and dietary habits. A follow-up INR seven days later was 2.4, and seven subsequent INR values were in the 2.0-2.5 range. DISCUSSION: L barbarum L. (family Solanaceae) is a commonly used Chinese herb considered to have a tonic effect on various organs. Any impact of an herbal product on the metabolism of S-warfarin, the enantiomer responsible for most of the anticoagulant activity, could alter the INR values. An herbal-drug interaction was suspected in this case. In vitro evaluation showed inhibition of S-warfarin metabolism by CYP2C9 by the tea of L. barbarum L.; however, the inhibition observed was weak, with a dissociation constant (Ki) value of 3.4 mg/mL, suggesting that the observed interaction may be caused by factors other than the CYP450 system. CONCLUSIONS: There is a potential herbal-drug interaction between warfarin and L. barbarum L., based on an increased INRvalue noted with concurrent use. Thus, combination of L. barbarum L. and warfarin should be avoided. Vigilance is needed with other herbal combinations taken with drugs of narrow therapeutic indices.

Anticoagulants↗
PubMed1999

Diltiazem increases tacrolimus concentrations.

OBJECTIVE: To describe a patient with increased tacrolimus concentrations due to a diltiazem drug interaction. CASE SUMMARY: A 68-year-old white man, four months following orthotopic liver transplantation secondary to hepatitis C and Laënnec's cirrhosis, was admitted to the intensive care unit for diarrhea, dehydration, and atrial fibrillation. He was stabilized on oral tacrolimus 8 mg twice daily, with a whole blood tacrolimus trough concentration of 12.9 ng/mL on admission. He was started on a continuous infusion of diltiazem for one day, followed by 30 mg orally every eight hours. Three days after admission, the patient became delirious, confused, and agitated; he was found to have a whole blood tacrolimus trough concentration of 55 ng/mL. The tacrolimus was withheld and diltiazem was discontinued. The tacrolimus concentrations fell over the next three days to 6.7 ng/mL, with a corresponding improvement in his mental status. The oral tacrolimus was restarted at 3 mg twice daily and increased gradually to 5 mg twice daily over the next four days; this produced tacrolimus trough concentrations between 9 and 10 ng/mL. DISCUSSION: Tacrolimus is known to be a substrate for P-glycoprotein and metabolized by CYP3A. Diltiazem inhibits CYP3A, P-glycoprotein, and tacrolimus metabolism in vitro. Although this interaction may have been predictable, this is the first detailed case report describing this clinically significant drug interaction. CONCLUSIONS: Diltiazem can dramatically increase tacrolimus concentrations and result in tacrolimus toxicity. Avoidance of this interaction or careful monitoring of tacrolimus concentrations along with tacrolimus dose reduction is recommended if diltiazem therapy cannot be avoided.

Aged↗