Search

Please cite this paper as: Lee C, Lin S, Lin C, Shih J, Lin T, Su Y. Clinical utility of array comparative genomic hybridisation for prenatal diagnosis: a cohort study of 3171 pregnancies. BJOG 2012;119:614-625. Objective To evaluate the clinical value of prenatal array comparative genomic hybridisation (CGH) in screening for submicroscopic genomic imbalances. Design Cross-sectional study. Setting Tertiary referral centre. Population From June 2008 to February 2011, 3171 fetuses underwent prenatal array CGH testing and karyotyping at the National Taiwan University Hospital. Indications for invasive prenatal diagnosis included abnormal karyotype, abnormal ultrasound, advanced maternal age and parental anxiety. Methods In all, 2497 fetuses were screened with 1-Mb resolution bacterial artificial chromosome array-based CGH, and 674 fetuses with 60-K oligonucleotide array-based CGH. Multiplex ligation-dependent probe amplification, fluorescence in situ hybridization, or 105-K oligonucleotide array CGH provided further confirmation. Main outcome measure Copy number variations identified by array CGH. Results Array CGH detected numerical chromosome anomalies in 37 (1.2%) fetuses, microdeletion/duplication in 34 (1.1%) fetuses, large deletion/duplication in 13 (0.4%) fetuses, benign copy number changes in 13 (0.4%) fetuses and variation of unknown clinical significance in five (0.2%) fetuses. Array CGH was effective in identifying submicroscopic genomic imbalance in fetuses with de novo balance translocations (2/17, 1.8%), supernumerary marker chromosomes (3/6, 50%), and abnormal prenatal ultrasound findings (33/194, 17.0%). Array CGH detected microdeletions/duplications in 12 fetuses with normal karyotype. Conclusion Prenatal array CGH is effective in screening for submicroscopic genomic imbalance. Array CGH may add 8.2% to the diagnostic field, compared with conventional karyotyping, for fetuses with abnormal ultrasound results, and is particularly useful in fetuses with karyotypic balanced translocation or marker chromosomes. There is a 0.52% baseline risk of submicroscopic genomic imbalance, even in women with an uneventful prenatal examination. [ABSTRACT FROM AUTHOR]

Setting: Taipei City, Taiwan., Objectives: To evaluate prescribing practices for anti-tuberculosis drugs in the treatment of tuberculosis (TB)., Method: Medical audit of the medical charts of all patients notified and treated for TB in Taiwan in 2003 to determine the treatment regimens prescribed and to compare these with recommended dosages., Results: A total of 24 different anti-tuberculosis regimens were prescribed. Of 1700 patients notified, 1096 (64.5%) had their body weight recorded. Of 506 patients prescribed a three-drug fixed-dose combination (FDC), the dosage was adequate in 374 (73.9%), too low in 100 (19.8%) and too high in 32 (6.3%). Of 75 patients prescribed a two-drug FDC, the dosage was adequate in 57 (76.0%), too low in 15 (20.0%) and too high in 3 (4.0%). Of 481 patients prescribed rifampicin, the dosage was adequate in 302 (62.8%), too low in 152 (31.6%) and too high in 27 (5.6%). Of 451 patients prescribed isoniazid, the dosage was adequate in 396 (87.8%), too low in 29 (6.4%) and too high in 26 (5.8%)., Conclusion: The prescribing practices for anti-tuberculosis drugs were substandard and need improvement. These findings imply that the National TB Programme needs strengthening.

Setting: National Taiwan University Hospital, Taipei, Taiwan., Objective: To study the variations in the NRAMP1 gene using five genotypes (274C/T, 577-18G/A, A318V, D543N and 3' untranslated region [UTR]), and the susceptibility of tuberculosis and HIV infection in Taiwanese., Design: The study sample included 49 patients with tuberculosis, 48 healthy control subjects and 60 HIV-infected patients. The polymerase chain reaction (PCR) products amplified from their genomic DNA were subjected to restriction enzyme digestion and were analysed using agarose gel electrophoresis., Results: A318V was not polymorphic in the studied population. Only D543N and 3'UTR were more heterozygous. In 274 C/T and 577-18G/A, the allele frequencies showed the predominant type to be the homozygous patterns C/C (94%) and G/G (94%), respectively. There were no statistically significant differences between the tuberculosis patients and the healthy control subjects. Despite the high susceptibility to Mycobacterium tuberculosis in HIV-infected patients, genotypic frequencies in the HIV-positive patients were not significantly different between tuberculous (n = 29) and non-tuberculous patients (n = 31). In comparison with previous studies, there were significant differences between different ethnic groups in allele frequencies for 274C/T, D543N and 3'UTR., Conclusion: The allele and genotype of NRAMPI polymorphism among Taiwanese differed from those of Caucasians, Africans and Hispanics. No allelic associations were identified between the NRAMP1 alleles and tuberculosis susceptibility.

G1P[6] rotaviruses were demonstrated previously to be associated with the neonatal nursery outbreak of gastroenteritis in Changhua Christian Hospital that is located in the central region of Taiwan, from September 1994 to May 1995. Meanwhile, rotaviruses were detected in children hospitalized for acute gastroenteritis. Our study characterizes the rotaviruses associated with the nursery outbreak by using genetic approaches. Nucleotide sequence analysis revealed that the VP7 genes of the nursery rotaviruses were distinct from those of the strains circulating in the community. The G1P[6] rotaviruses recovered from the nursery were closely related to another neonatal G1P[6] strain from the northern region of Taiwan in both the VP4 and VP7 genes. The VP4 genes of these nursery strains differed from those of the P[6] human reference strains 1076, M37, RV3, and ST3. Apparently, these nursery rotaviruses were distinct from the strains circulating in the community and seemed to be a variant when compared with P[6] strains reported previously.

Objective: To evaluate vascular endothelial growth factor (VEGF) as a marker for predicting lymph node metastasis and an independent prognostic factor of early-stage cervical carcinoma., Methods: One hundred thirty-five women with stage IB-IIA cervical carcinoma had radical abdominal hysterectomies and pelvic lymph node dissections. Intratumoral cytosol VEGF concentrations were assayed with enzyme immunoassay. Histopathologic items and cytosol VEGF-influencing clinical outcomes were compared., Results: Twenty-two women (16.3%) who had disease recurrence had higher levels of cytosol VEGF (1020 versus 112 pg/mg protein, P <.001) than those without recurrence. Using a cutoff value of 400 pg/mg protein resulted in best sensitivity of 75%, best specificity of 70%, positive predictive value of 41%, and negative predictive value of 92%. Only overexpressed cytosol VEGF (hazard ratio 6.44, P <.001) was an independent prognostic factor of disease-free survival. The overexpressed cytosol VEGF (hazard ratio 4.50, P =.021) and positive lymphovascular emboli (hazard ratio 4.11, P =.045) were independent prognostic factor of overall survival., Conclusion: Cytosol VEGF might be a biomarker for the status of pelvic lymph nodes in early-stage cervical carcinoma and an independent prognostic indicator of its outcome.

Rotavirus infection is the leading cause of childhood gastroenteritis. We retrospectively reviewed cases of rotavirus gastroenteritis at National Taiwan University Hospital from January 1993 to December 1997. During the study period there were 429 patients with rotavirus infection with ages ranging from 1 day to 16 years with a median of 13 months. The male-to-female ratio was 1.2:1. Infection occurred before the age of 2 years old in 76% of patients. The seasonal peak occurred in the late winter and early spring during 1993 to 1996, but the case number increased in late spring and summer in 1997. The G serotype of the rotavirus was identified in 302 patients (70%). Vomiting and dehydration developed more frequently following infection with G1 rotaviruses, while an increased frequency of seizures was noted following G2 infection; the differences were not statistically significant. One patient had two episodes of infection; the first one was caused by G1 rotavirus, and the strain causing the second infection could not be typed. In conclusion, the results suggest that there is a strong seasonal variation in the incidence and characteristics of rotavirus infection in Taipei area. The infections caused by G1 and G2 rotaviruses were clinically indistinguishable.

Enteric adenoviruses (EAds), including type 40 (Ad40) and 41 (Ad41), can cause acute and severe diarrhea in young children. To delineate the epidemiological features of pediatric EAds infection in Taiwan, we conducted a retrospective study of all cases of EAds gastroenteritis in children treated at National Taiwan University Hospital for the period from July 1993 to December 1997. Stool samples were tested for the presence of Ad40 or Ad41 by enzyme immunoassay (EIA). A total of 64 cases of EAds infection in 63 children aged from 8 days to 81 months old with a median age of 9.5 months treated during the study period were identified. The male-to-female ratio was 1.63 (39/24). No obvious seasonal clustering of EAds cases was noted. Most patients (76.6%) were infected before the age of 2 years. Clinical features included diarrhea (96.9%), fever (54.7%), vomiting (45.3%), mild dehydration (43.8%), symptoms of upper respiratory tract infection (21.9%), and abdominal pain (12.5%). Analysis of fecal samples in patients with diarrhea showed watery diarrhea in 72.2%, diarrhea with mucus in 20%, diarrhea with blood in 3.1% and diarrhea with mucus and blood in 1.6 % of all patients. Nearly one-half (43.5%) of the patients had diarrhea for more than 7 days. Thirty-seven patients (57.8%) were hospitalized due to gastroenteritis or other unrelated diseases, and 11 patients (17.2%) acquired enteric adenovirus infection during hospitalization for other underlying disease. Twelve patients (18.8%) had mixed infections, which included rotavirus, respiratory syncytial virus (RSV) and Salmonella species. There were no deaths in this series. The findings of this study suggest that EAds are important etiologic microbes of pediatric gastroenteritis.

The genetic diversity of human immunodeficiency virus (HIV) type 1 (HIV-1) has been characterized mainly by analysis of the env and gag genes. Information on the vpu genes in the HIV sequence database is very limited. In the present study, the nucleotide sequences of the vpu genes were analyzed, and the genetic subtypes determined by analysis of the vpu gene were compared with those previously determined by analysis of the gag and env genes. The vpu genes were amplified by nested PCR of proviral DNA extracted from 363 HIV-1-infected individuals and were sequenced directly by use of the PCR products. HIV-1 subtypes were determined by sequence alignment and phylogenetic analysis with reference strains. The strains in all except one of the samples analyzed could be classified as subtype A, B, C, E, or G. The vpu subtype of one strain could not be determined. Of the strains analyzed, genetic subtypes of 247 (68.0%) were also determined by analysis of the env or gag gene. The genetic subtypes determined by vpu gene analysis were, in general, consistent with those determined by gag and/or env gene analysis except for those for two AG recombinant strains. All the strains that clustered with a Thailand subtype E strain in the vpu phylogenetic analyses were subtype E by env gene analysis and subtype A by gag gene analysis. In summary, our genetic typing revealed that subtype B strains, which constituted 73.8% of all strains analyzed, were most prevalent in Taiwan. While subtype E strains constituted about one-quarter of the viruses, they were prevalent at a higher proportion in the group infected by heterosexual transmission. Genetic analysis of vpu may provide an alternate method for determination of HIV-1 subtypes for most of the strains, excluding those in which intersubtype recombination has occurred.

This study is a novel approach in establishing the maternal age-specific risk for Down syndrome screening in an Asian population. The relative frequency by one-year maternal age interval in women who had live births in the Taiwan area between 1975 and 1995 was used as the age-specific distribution of women who had unaffected pregnancies. Data about Down syndrome live births were obtained from the Taiwan Down Syndrome Association to establish the age distribution of women who had Down syndrome live births. The relative frequencies and the likelihood ratio by one-year maternal age interval was calculated and smoothed by running median and moving average smoothing methods. The age-specific risk was established by multiplying the total population risk by the likelihood ratio of the specific maternal age. The total live births in the Taiwan area between 1975 and 1995 were 7,232,689. A total of 527 cases of Down syndrome live births were registered in the Taiwan Down Syndrome Association. A total of 466 cases (88.43 per cent) of Down syndrome live births occurred before age 35, which was higher than occidental reports. This study established the first sizeable database of maternal age-specific risk for Down syndrome in an Asian population.

To disclose the impact of human immunodeficiency virus (HIV) infection on the tuberculosis epidemic in Taiwan, we prospectively screened for HIV infection in patients with active pulmonary tuberculosis. A total of 378 patients who were admitted to the Taiwan Provincial Chronic Disease Control Bureau from January through December 1996 were enrolled. HIV serologic testing was performed by enzyme-linked immunosorbent assay (ELISA). A positive ELISA test was confirmed by Western blot analysis. One patient was infected with HIV. We conclude that the impact of HIV infection on the epidemic of tuberculosis in Taiwan is not significant at present.

This study was aimed at assessing the efficacy and tolerability of rifabutin for the re-treatment of cases of chronic, multidrug-resistant pulmonary tuberculosis. The study design was self-controlled, single center. Rifabutin was administered as part of an individual-tailored multidrug regimen. In-patients suffering from pulmonary tuberculosis, infected with Mycobacterium tuberculosis bacilli resistant to isoniazid, rifampicin and other drugs with progressive disease unresponsive to prior courses with standard anti-tuberculosis medications were treated. Overall, 43 patients were enrolled and treated with rifabutin at 300 or 450mg/day according to body weight in conjunction with available anti-tuberculous drugs for a mean time of 353 days (range 42-678). Of these, 36 met all eligibility criteria (i.e. positive baseline culture of sputum with bacilli resistant to rifampicin at least) and were retained for the analysis of efficacy. Seventeen patients (47%) achieved a sustained conversion to a negative culture of sputum in a mean time of 47.7 days with a range of 14-120 days. Treatment prevented deterioration in most patients and resulted in clinical and radiological cure or marked improvement in more than half of cases. No correlation was found between treatment outcome and use of medication concomitant to rifabutin or susceptibility of bacilli to the drugs used. Four deaths occurred due to disease progression, in no case being related to study drugs. Ten patients reported a total of 18 adverse events that led to treatment discontinuation in 5 cases. Rifabutin should be considered for inclusion in regimens for cases of pulmonary multidrug-resistant tuberculosis which fail to respond to previous therapy.

Eighty-seven patients with multidrug-resistant tuberculosis (MDR-TB) diagnosed between 1988 and 1990 were treated with isoniazid and at least three other effective second-line drugs based on in vitro susceptibility tests. Of these patients, 10% failed to adhere to the regimen and 43% remained sputum positive after 6 months of treatment. Only 47% showed sputum conversion within 6 months of treatment and 12% of them relapsed during the first year of follow-up. From September 1987 to July 1989, 36 patients with MDR-TB were treated with a regimen containing rifabutin, isoniazid and at least three other susceptible drugs. Only 47% achieved a sustained sputum conversion. Four died during treatment due to disease progression. From March 1992 to July 1993, 17 cases of MDR-TB were treated with an ofloxacin-containing anti-TB regimen for 12-24 months. Two failed to adhere to the regimen for more than 1 month during the first 6 months of therapy. Among the remaining 15, 26% failed to achieve sputum conversion, 73% achieved bacterial conversion, 9 within 1 month and the other 2 within 2 months. No significant adverse effect was associated with ofloxacin use. We concluded that ofloxacin is a better choice among the more toxic and less potent second-line drugs, and should be used along with other anti-TB drugs in treating patients with MDR-TB.

Objective: To determine the frequency of intrauterine rubella infection in Taiwan., Methods: One hundred three pregnant women with evidence of rubella infection were enrolled. Congenital rubella infection was diagnosed by testing specific immunoglobulin (Ig) M in fetal cord serum obtained from funipuncture or amniotic fluid culture. The fetal outcomes were evaluated by ultrasonic examination, specific antibody detection in cord blood at birth, and complete physical examination during early childhood., Results: Prenatal diagnosis was possible in 95 of 103 fetuses, 93 by funipuncture and two by amniocentesis. Five intrauterine rubella infections were detected prenatally, and another one was diagnosed after birth. The intrauterine infection rates were 10.0, 11.8, 2.9, and 6.5% after maternal infection at 1-10, 11-14, 15-19, and 20-29 gestational weeks, respectively. Among the six fetuses with serologic evidence of congenital infection, one had congenital rubella syndrome with sensorineural deafness, two were terminated during the second trimester, two others were normal, and one was lost to follow-up. With the exception of the infant with clinical congenital rubella syndrome, no evidence of rubella defects was found in the other 81 children who received follow-up to 2-4 years old., Conclusion: The risk of congenital rubella infection in seropositive pregnant women is relatively low in Taiwan.

From 1981 to 1990, 10,167 clinical specimens were collected at National Taiwan University Hospital from the cases with suspected viral infections. Three hundred of herpes simplex virus (HSV) were isolated from these samples (isolation rate; 3.0%). One hundred and fifty-one strains were isolated from non-genital, and 149 strains from genital areas. HSV strains were typed by direct immunofluorescence staining technique. The type specific monoclonal antibodies were used in the test. Most of the HSV strains isolated from non-genital areas were type 1 (HSV-1) (147/151, 97.4%) whereas most of the strains from genital areas were type 2 (HSV-2) (140/149, 94.0%). All nine strains of HSV-1 isolated from genital areas were from female patients. The predominance of HSV-1 in non-genital area infections, and of HSV-2 in genital area infections, did not change during the ten years under review.

Poliovirus type 1 strains recovered from patients with poliomyelitis during the epidemic of 1982, were distinct antigenically from Sabin-1 strain by comparing homologous and heterologous neutralization rate constants of Sabin-1 specific antiserum. With the reproductive capacity at 40 degrees C, these isolates could be easily differentiated from vaccine strain. It was suggested that the epidemic of poliomyelitis in 1982 was not caused by vaccine strain. The 24 isolates reacted with LSc and/or Sabin-1 antisera to the same extent. It was speculated that they might be antigenically similar if not identical. Three isolates which were collected from the later part of epidemic formed small plaques at 40 degrees C. Rabbit antisera against poliovirus strains 3844, Sabin-1, Mahoney and Brunhilde were produced. Antigenic relatedness among the strains was tested by kinetic neutralization. The strain 3844 was distinct from Brunhilde, Mahoney and Sabin-1. Asymmetric cross-reactions between Mahoney and Sabin-1 strains were clearly demonstrated.