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L Y Hsu

Publications and source records attributed to L Y Hsu.

At least 19 recordsLinked to original sources

Maternal serum alpha-fetoprotein screening and fetal chromosome anomalies: is lowering maternal age for amniocentesis preferable?

We have compared the cytogenetic abnormalities diagnosed prenatally in 1,098 patients referred for amniocentesis because of low maternal serum alpha-fetoprotein (MSAFP) to those of 445 patients whose indication was elevated MSAFP and those of 361 patients who had amniocentesis for "maternal anxiety." Autosomal trisomies, sex chromosome aberrations, and various structural rearrangements were detected in all 3 groups and actually exceeded the age-related incidence estimates. The frequency of chromosome anomalies in cases studied because of "maternal anxiety" with no prior screening was similar to that in the group referred for low MSAFP (1.38 and 1.27%, respectively). A relatively higher frequency (2.02%) was detected in the group whose indication was elevated MSAFP. Maternal serum screening is designed primarily to recalculate risk figures for Down syndrome, but not for other major chromosome abnormalities. The concept of prenatal screening for chromosome aberrations must therefore be reevaluated. We think that efforts should be directed at making amniocenteses more accessible to patients who request it. "Lowering" maternal age limits to 30 would encompass a greater proportion of pregnancies at risk and would be a step toward more effective prenatal diagnosis for chromosome abnormalities.

Adult

Proposed guidelines for diagnosis of chromosome mosaicism in amniocytes based on data derived from chromosome mosaicism and pseudomosaicism studies.

Currently, accepted protocol which has been developed at the Prenatal Diagnosis Laboratory of New York City (PDL) requires that when a chromosome abnormality is found in one or more cells in one flask, another 20-40 cells must be examined from one or two additional flasks. Chromosome mosaicism is diagnosed only when an identical abnormality is detected in cells from two or more flasks. In a recent PDL series of 12,000 cases studied according to this protocol, we diagnosed 801 cases (6.68 per cent) of single-cell pseudomosaicism (SCPM), 126 cases (1.05 per cent) of multiple-cell pseudomosaicism (MCPM), and 24 cases (0.2 per cent) of true mosaicism. Pseudomosaicism (PM) involving a structural abnormality was a frequent finding (2/3 of SCPM and 3/5 of MCPM), with an unbalanced structural abnormality in 55 per cent of SCPM and 24 per cent of MCPM. We also reviewed all true mosaic cases (a total of 50) diagnosed in the first 22,000 PDL cases. Of these 50 cases, 23 were sex chromosome mosaics and 27 had autosomal mosaicism; 48 cases had numerical abnormalities and two had structural abnormalities. Twenty-five cases of mosaicism were diagnosed in the first 20 cells from two flasks, i.e., without additional work-up, whereas the other 25 cases required extensive work-up to establish a diagnosis (12 needed additional cell counts from the initial two culture flasks; 13 required harvesting a third flask for cell analysis). Our data plus review of other available data led us to conclude that rigorous efforts to diagnose true mosaicism have little impact in many instances, and therefore are not cost-effective. On the basis of all available data, a work-up for potential mosaicism involving a sex chromosome aneuploidy or structural abnormality should have less priority than a work-up for a common viable autosomal trisomy. We recommend revised guidelines for dealing with (1) a numerical versus a structural abnormality and (2) an autosomal versus a sex chromosome numerical aneuploidy. Emphasis should be placed on autosomes known to be associated with phenotypic abnormalities. These new guidelines, which cover both flask and in situ methods, should result in more effective prenatal cytogenetic diagnosis and reduced patient anxiety.

Amniocentesis

In vitro antibacterial activities of ticarcillin alone and ticarcillin plus clavulanic acid against beta-lactamase producing and non-producing microorganisms.

A total of 818 clinical bacterial isolates were tested for the production of beta-lactamase by rapid chromogenic cephalosporin method and for the susceptibility to ticarcillin alone and in combination with clavulanic acid (2 micrograms/mL) by agar dilution method. These included 83 strains of methicillin-sensitive Staphylococcus aureus (MSSA), 31 of methicillin-resistant S. aureus (MRSA), 49 of Neisseria gonorrhoeae, 58 of Haemophilus influenzae, 112 of Escherichia coli, 118 of Klebsiella pneumoniae, 58 of Proteus mirabilis, 30 of Proteus vulgaris, 60 of Serratia marcescens, 113 of Enterobacter cloacae, 60 of Pseudomonas aeruginosa and 46 of Bacteroides fragilis. The results revealed that 46.6% of P. mirabilis, 53.4% of H. influenzae, 57.1% of N. gonorrhoeae, 80% of P. vulgaris, 83.9% of MRSA, 85.6% of MSSA, 87.5% of E. coli, 91.7% of S. marcescens, 95.7% of B. fragilis, 98.2% of E. cloacae, and 100% of K. pneumoniae and P. aeruginosa strains produced beta-lactamase. In general, beta-lactamase nonproducers were more susceptible to ticarcillin than beta-lactamase producers. The ranges of minimum inhibitory concentrations (MICs) of ticarcillin for beta-lactamase nonproducers of MSSA, MRSA, H. influenzae, E. coli, P. vulgaris, S. marcescens, E. cloacae, B. fragilis and beta-lactamase producers of MSSA, H. influenzae strains were all within the in vitro susceptible range. The presence of clavulanic acid resulted in a significant enhancement of the antibacterial activity of ticarcillin against beta-lactamase producers of MRSA, N. gonorrhoeae, E. coli, K. pneumoniae, P. mirabilis, P. vulgaris and B. fragilis strains. Clavulanic acid had no synergistic activity for ticarcillin against S. marcescens, P. aeruginosa and E. cloacae.

Bacteria

Epidemiologic investigation of nosocomial outbreak of methicillin-resistant Staphylococcus aureus by plasmid pattern analysis.

Nosocomial infections caused by methicillin-resistant Staphylococcus aureus (MRSA) have become an important problem with increasing frequency. In order to learn if plasmid pattern analysis can be used in epidemiologic investigations of MRSA infections, the authors did plasmid extractions of 70 MRSA stock isolates using a rapid lysostaphin lysis method. All isolates carried at least one plasmid. Most of the isolates had one large plasmid of 24-28 megadaltons (Md). Many also carried one or two small plasmids. Accordingly, 12 different patterns were identified. From these background results, we applied this method to the investigation of two small nosocomial outbreaks of MRSA infection. It was found that the analysis of plasmid pattern and restriction endonuclease analysis are more discriminative than antibiograms. Strains with the same antibiograms can be different by plasmid analysis. It is concluded that the plasmid pattern with a restriction endonuclease analysis study is a reliable method for epidemiologic study of MRSA infections.

Cross Infection

A revisit of trisomy 20 mosaicism in prenatal diagnosis--an overview of 103 cases.

One hundred and three cases with prenatal diagnosis of trisomy 20 mosaicism through amniocentesis were reviewed. Approximately 90 per cent (90/101) of the cases were associated with grossly normal phenotype. It is likely that, in the majority of cases, cells with trisomy 20 were extraembryonic in origin or largely confined to the placenta. However, in some cases, the cells with trisomy 20 were confined to certain specific fetal organs or tissues such as kidney, skin, etc. Cytogenetic follow-up studies in liveborns should include a culture from urine sediment.

Amniocentesis

Antimicrobial activities of piperacillin alone and in combination with tazobactam against beta-lactamase-producing bacteria.

Tazobactam (YTR 830), a new beta-lactamase inhibitor, was evaluated for its effect in combination with piperacillin, a broad spectrum, but beta-lactamase sensitive, penicillin, against 14 common bacteria. A total of 1,086 clinical isolates from different clinical specimens were tested for beta-lactamase production by the rapid chromogenic cephalosporin method. Their susceptibilities to piperacillin alone and in combination with tazobactam in a ratio of 8:1 by the agar dilution method were evaluated. The percentage of beta-lactamase producing strains ranged from 14.5% to 100% in these tested species. In general, the beta-lactamase producers were more resistant to piperacillin than the beta-lactamase nonproducers with higher minimal inhibitory concentrations (MICs). For the beta-lactamase producers, tazobactam decreased the MICs of piperacillin prominently in methicillin-resistant Staphylococcus aureus, Neisseria gonorrhoeae, Haemophilus influenzae, Escherichia coli, Proteus mirabilis, Morganella morganii, Salmonella species and Bacteroides fragilis, with a 4-fold or greater decrease in MIC50, MIC90 and the geometric mean of MIC. For Serratia marcescens and Pseudomonas aeruginosa, the MICs did not change after adding tazobactam. For other species, there was a moderate decrease in MICs. We conclude that tazobactam is an effective beta-lactamase inhibitor for increasing the antimicrobial activity of piperacillin against beta-lactamase producing strains of many species of bacteria.

Ampicillin Resistance

Antibacterial activities of amoxicillin alone and in combination with clavulanic acid correlated with beta-lactamase production.

Amoxicillin, a beta-lactam antibiotic, was tested for its effect in combination with clavulanic acid, a beta-lactamase inhibitor, against 9 species of bacteria isolated from clinical specimens. A total of 698 strains of bacteria were tested for beta-lactamase production by the rapid chromogenic cephalosporin method. Their susceptibilities to amoxicillin alone and in combination with clavulanic acid were tested by the agar dilution method. The percentage of beta-lactamase producing strains ranged from 46.6% in Proteus mirabilis to 100% in Klebsiella pneumoniac. In general, beta-lactamase nonproducers were more susceptible to amoxicillin than beta-lactamase producers. For beta-lactamase producers, clavulanic acid decreased the MICs of amoxicillin prominently in strains of Neisseria gonorrhoeae, Haemophilus influenzae, Escherichia coli, K. pneumoniae, P. mirabilis, Enterobacter cloacae and Bacteroides fragilis, when combining clavulanic acid with amoxicillin in the ratio of 1:2. Their MIC50s, MIC90s and geometric means of MICs all decreased 4 folds or greater. For beta-lactamase non-producing strains, the MICs did not show significant differences by adding clavulanic acid in most species we tested, including methicillin-sensitive Staphylococcus aureus, N. gonorrhoeae, H. influenzae, Proteus vulgaris and E. cloacae.

Amoxicillin

Coaggregation of oral Candida isolates with bacteria from bone marrow transplant recipients.

In vitro coaggregation between Candida species isolated from immunosuppressed bone marrow transplant recipients and oral bacteria was investigated. Each Candida strain showed a different pattern of coaggregation with the 22 bacterial strains studied. Two strains of Lactobacillus amylovorus isolated from separate bone marrow transplant patients and Fusobacterium nucleatum (VPI 10197) coaggregated with all Candida strains. Ten bacterial strains showed no coaggregation with the Candida strains. A variety of inhibition patterns were observed when coaggregating strains were first incubated with various sugars or subjected to heat treatment. Positive and negative results were generally consistent with all Candida strains. On the basis of the culture characteristics of the oral rinse specimens, relationships between the colonization of bacteria and yeasts and in vitro coaggregation were suggested.

Bacteria

[Epidemiologic study of pathogens causing nosocomial infections].

Nosocomial infection is a global problem. It significantly adds to the expected duration of hospitalization resulting with an increased economic burden and represents a leading cause of death. The characteristics of nosocomial infection vary from country to country and also changes with time. In order to understand the pathogens causing nosocomial infection in the large teaching hospital in Taiwan, we collected and analysed the surveillence data of nosocomial infection at the National Taiwan University Hospital from 1981 to 1989. We found that the nosocomial infection rate had been around 4-5% annually since 1981 till 1989. As ranked according to the site of infection, surgical wound infections were the most common, followed by the urinary tract, respiratory tract, and blood stream infections. However, the incidence of surgical wound infections had decreased gradually. About one third of nosocomial infections were caused by multiple microorganisms. The most frequently isolated pathogen has changed from Escherichia coli in early years to Pseudomonas aeruginosa in the most recent years. Gram-negative aerobic bacteria has been the major pathogens resulting in nosocomial infections for the past 9 years, accounting for 55-66%. In contrast, fungi have increased rapidly from 1.8% of total isolates in 1981 to 7.7% in 1989. Gram-positive cocci have also increased in recent years. The leading pathogen by infection site was P. aeruginosa in surgical wound infections, E. coli in urinary tract infections, and P. aeruginosa in respiratory tract infections. In earlier years E. coli was the major isolate in bacteremic cases, but glucose non-fermenters, including P. aeruginosa, Acinetobacter calcoaceticus and others, plus Enterobacter species-emerged as the major pathogens of recent years.(ABSTRACT TRUNCATED AT 250 WORDS)

Cross Infection

Prenatal diagnosis of 45,X/46,XY mosaicism--a review and update.

A total of 54 cases with prenatal diagnosis of 45,X/46,XY mosaicism was reviewed. Of 47 cases with information on phenotypic outcome, 42 cases (89.4 per cent) were reported to be associated with a grossly normal male phenotype. Three cases (6.4 per cent) were diagnosed as having mixed gonadal dysgenesis with internal asymmetrical gonads. Two other cases were questionably abnormal. In 40 cases with successful cytogenetic confirmatory studies, the overall rate of cytogenetic confirmation of 45,X/46,XY from tissues derived from fetus/liveborn/placenta was 70.0 per cent. This review shows a major difference in the phenotypic outcome between postnatal diagnosis and prenatal diagnosis. Due to the ascertainment bias, almost all known patients with postnatal diagnosis of 45,X/46,XY mosaicism are phenotypically abnormal. Therefore, caution must be used in translating information derived from postnatal diagnosis to prenatal diagnosis. This review calls for collection of more data on 45,X/46,XY mosaicism diagnosed prenatally, more long-term follow-up of liveborn infants, and pathological studies of all abortuses. Emphasis is placed also on the importance of genetic counselling, ultrasound examination, and cytogenetic confirmation.

Amniotic Fluid

A rare case of 68,XX triploidy diagnosed by amniocentesis.

68,XX triploidy was found in the amniotic fluid cell culture of a 40-year-old patient. Elective termination of the pregnancy revealed a fetus with multiple congenital anomalies. While this case does show some common features with monosomy X, a greater similarity to the triploidy syndrome is observed.

Abnormalities, Multiple

Amniotic fluid alpha-fetoprotein levels and prenatal diagnosis of autosomal trisomies.

Pregnancies with fetal trisomy 21 have been associated with low amniotic fluid alpha-fetoprotein levels (AFAFP). This observation led to the suggestion that low AFAFP levels be used as a criterion for completion of a chromosomal analysis in patients who are not otherwise at increased risk for a fetal chromosome abnormality and in whom karyotyping might not have been completed for economic reasons. In order to assess the usefulness of such criteria, we reviewed the AFAFP levels of 90 cases of fetal trisomy 21, 23 cases of trisomy 18, and 10 cases of trisomy 13. These were compared with 2400 control samples with normal chromosome constitution. AFAFP levels were generally lower in pregnancies with trisomy 21, showing a median value of 0.72 MoM. However, 40 per cent of the trisomy 21 samples had AFAFP values greater than 0.8 MoM and 20 per cent were over 1.0 MoM. These data imply that over 50 per cent of Down syndrome cases might have been missed using a cut-off level of 0.70 MoM for completion of chromosome analysis. Using a higher cut-off level will leave only a small percentage of samples unkaryotyped. The distribution of AFP levels in trisomy 13 and 18 is no different from controls; we therefore believe that fetal karyotyping should be completed in every amniotic fluid sample obtained.

Amniotic Fluid

His-426 of the Pseudomonas aeruginosa exotoxin A is required for ADP-ribosylation of elongation factor II.

Exotoxin A (ETA) is recognized as the most toxic product associated with the opportunistic pathogen Pseudomonas aeruginosa. Identification of the amino acids in the polypeptide sequence that are required for toxin activity is critical for vaccine development. By defining the nucleotide sequence of the structural gene of a mutant that encodes an enzymatically inactive ETA (CRM 66), we identified an essential amino acid (His-426), which is involved in the ADP-ribosyltransferase activity associated with functional ETA. A monoclonal antibody that inhibits ETA enzymatic activity in vitro fails to react with ETA variants that have a His 426----Tyr substitution. Several mono-ADP-ribosylating toxins, including diphtheria and pertussis toxins, within the primary amino acid sequences carry a histidine residue that is conserved in spacing and in location with respect to other critical residues. Analysis of the three-dimensional structure of ETA revealed that His-426 is not associated with the proposed NAD+ binding site. These findings should be useful for the design and construction of toxin vaccines.

ADP Ribose Transferases

The centralized prenatal genetics screening program of New York City III: The first 7,000 cases.

The Prenatal Diagnosis Laboratory of New York City (PDL) is a regional program for the prevention of genetic diseases. The administrative aspects of the establishment of the laboratory were described in papers I [Hsu, 1981] and II [Hsu and Benn, 1981] in this series. We now report our experience of the first 7,000 referrals to the laboratory. The laboratory achieved a success rate of 99.5% in obtaining a diagnosis. The frequency with which a repeat amniocentesis was required was 1.9%, usually attributable to inadequate initial amniotic fluid volume or condition. Cases were completed in an average time of 20.82 days. A total of 149 (2.13%) cytogenetic abnormalities were detected. There were 59 nonmosaic autosomal trisomies and 29 sex chromosome abnormalities. The incidence of unbalanced structural abnormalities (0.186%) was much higher than that reported in surveys of newborn infants largely because of the prenatal detection of cases with supernumerary chromosomes. The incidence of balanced structural abnormalities was also considerably higher than that found in surveys of the newborn population, in part because of the detection of subtle familial pericentric inversions of common chromosome regions (inv(Y)(p11q11), inv(2) (p11q13), and inv(1)(p11q13)). The incidence of cases with multiple independent chromosome abnormalities was no higher than expected by chance. A high incidence of mosaicism, pseudomosaicism, and maternal cell contamination was found. Screening for neural tube defects accounted for the detection of a further 16 abnormalities. Nearly all women with severely abnormal fetuses (trisomy 13, 18, 21) elected to terminate their pregnancy whereas only 62% of patients with a prenatally diagnosed sex chromosome abnormality elected to terminate their pregnancies. Full details of follow-up and confirmatory studies for unusual diagnoses are reported. Utilization of prenatal diagnosis in the New York City area has increased sharply since PDL became operational. The laboratory's success illustrates the role of a prenatal diagnosis laboratory that provides a service independent of the patient's financial status. The experience further shows the high degree of acceptance of prenatal diagnosis by individuals at high risk for a child with a genetic disorder.

Amniocentesis

Prenatal diagnosis of trisomy 20 mosaicism.

Three cases of trisomy 20 mosaicism in amniotic fluid cell cultures are described. Two of the pregnancies resulted in normal full-term infants. The third pregnancy was terminated and revealed a phenotypically normal fetus. A review of five previously reported cases is presented. Explanations of these findings include in vitro nondisjunction, culture of extraembryonic tissue, and true fetal mosaicism. The diagnostic dilemma this presents is discussed.

Adult

Trisomy 13 in bone marrow cells in acute myelocytic leukemia and myelofibrosis.

We have identified trisomy 13 in two additional patients with hematologic malignancies involving the hematopoietic stem cell: a 75-year-old female with acute myelocytic leukemia and a 64-year-old female with agnogenic myelofibrosis and myeloid metaplasia. Chromosome analysis of the direct bone-marrow preparation showed 100% of cells with trisomy 13 in the first and 10% of cells in the second. We also previously reported a patient with Ph1 negative chronic myelogenous leukemia in whom 100% of the marrow cells showed an identical trisomy. The probability of finding three such patients in our case material was calculated to be 0.05--0.08, implying that trisomy 13 may be another nonrandom chromosomal aberration associated with malignancies of hematopoietic pluri-potent stem cell.

Aged