Prevalence and oncologic impact of chronic kidney disease for upper tract urothelial carcinoma in endemic area.

OBJECTIVE: This study aimed to assess the impact of preoperative chronic kidney disease (CKD) on the oncological outcomes of patients with upper tract urothelial carcinoma (UTUC) who underwent standard radical nephroureterectomy (RNU). METHODS: A total of 1172 UTUC patients who received RNU at a single center in Taiwan between February 2005 and August 2019 were included. The patients were categorized into two groups based on their preoperative CKD stage: CKD stage ≤3 (811 patients) and CKD stage >3 (361 patients). The estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease (MDRD) formula. The study investigated the oncological outcomes, including intravesical recurrence, non-urothelial recurrence, and cancer-specific mortality, stratified by preoperative CKD status. RESULTS: The main findings indicated that UTUC patients with CKD stage >3 in Taiwan exhibited a higher proportion of females (p < 0.001), a greater history of concurrent bladder cancer (p = 0.003), more multifocal tumor behavior (p < 0.001), a higher incidence of carcinoma in situ (p = 0.008), increased rates of intravesical recurrence (p < 0.001), a lower prevalence of smoking history (p = 0.003), lower utilization of adjuvant chemotherapy (p < 0.001), reduced occurrence of non-urothelial recurrence (p < 0.001), and lower cancer-specific mortality (p = 0.006) compared to patients with CKD stage ≤3. Multivariate Cox regression analysis revealed significant differences in intravesical recurrence (p = 0.014) and non-urothelial recurrence (p = 0.006) between the CKD stage >3 and CKD stage ≤3 groups. The study also demonstrated that patients with concurrent bladder cancer and variant histology had higher rates of intravesical recurrence, non-urothelial recurrence, and cancer-specific mortality. The CKD stage >3 group exhibited lower rates of intravesical recurrence (p = 0.0014), higher rates of non-urothelial recurrence (p < 0.0001), and increased cancer-specific mortality (p = 0.0091) compared to the CKD stage ≤3 group in the 5-year free survival analysis. CONCLUSION: In Taiwan, UTUC patients with CKD stage >3 exhibit distinct characteristics compared to the general population with urothelial carcinoma. They are associated with a non-smoking status, a higher proportion of females, and less aggressive pathological features. Additionally, CKD stage >3 can serve as a clinical indicator for intravesical and non-urothelial recurrence. Further investigation into molecular aspects and treatment modifications for these patients is warranted.

A single-nucleotide polymorphism of the DAZL gene promoter confers susceptibility to spermatogenic failure in the Taiwanese Han.

BACKGROUND: Deleted in AZoospermia-like (DAZL) is an autosomal homologue of Y chromosome-linked DAZ gene located on chromosome 3p24. DAZL is only expressed in the gonads and is critical to germ cell development in different species. However, the regulation of DAZL has not been explored. METHODS: Reporter assays, electrophoretic mobility shift assays, supershift assays and bisulfate sequencing were used to identify the core promoter region of DAZL. Sequence analysis was used to identify single-nucleotide polymorphisms (SNPs) in the promoter region. A total of 337 infertile men with abnormal semen parameters and 203 fertile men with normal semen parameters were subjected to sequence analysis of the DAZL promoter region. RESULTS: The DAZL gene core promoter is located 1 kb upstream of the transcription start site. Three SNPs (-792G>A, -669A>C and -309T>C) were identified in our population. Of these three SNPs, -792G>A was more prevalent in the infertile men (P= 0.0005). Quantitative analysis revealed that genotypes of -792G>A had effects on sperm concentration (P= 0.0025) and motility (P= 1.5 × 10(-7)). The G to A substitution was associated with decreased binding of the nuclear respiratory factor-1 (NRF-1) to the promoter region and decreased reporter gene activity. CONCLUSION: We have identified the core promoter of the human DAZL gene. We also provide preliminary evidence for the role of a novel SNP of the DAZL gene promoter in human spermatogenic failure.

Association of polymorphisms/haplotypes of the genes encoding vascular endothelial growth factor and its KDR receptor with recurrent pregnancy loss.

BACKGROUND Vascular endothelial growth factor (VEGF) and its kinase insert domain receptor (KDR) play an important role in angiogenesis, and their gene expression patterns also suggest a close relationship with early pregnancy. However, limited information is available regarding the role of the VEGF system, especially its KDR receptor, in recurrent pregnancy loss (RPL). This study was conducted to investigate a genetic association between VEGF and its receptor gene (KDR) with idiopathic RPL. METHODS In this case-control study, 115 women who had experienced at least two consecutive spontaneous miscarriages (n= 62 women with two miscarriages, n= 53 with three or more) and 170 controls were included. A total of 14 tag single-nucleotide polymorphisms (SNPs) of VEGF and KDR were selected from the HapMap Web site and three functional SNPs [rs1570360 (-1154G/A) of VEGF; rs2305948 (V297I) and rs1870377 (Q472H) of the KDR gene] were genotyped using primer extension analysis. We further used multifactor dimensionality reduction analysis to evaluate gene-gene interactions. RESULTS One tag SNP (rs6838752) and the functional SNP (Q472H) of the KDR gene were in complete linkage and showed significant differences between patients and controls (P< 0.05). The frequencies of haplotypes of VEGF (A-T-G haplotype) and KDR (A-C-A-T-G haplotype) showed significant differences in patients versus controls (P< 0.05). All comparisons with controls remained significant when the subgroup of women with three or more miscarriages was analyzed. CONCLUSIONS VEGF and its receptor gene (KDR) are associated with idiopathic RPL. The VEGF/KDR system jointly contributes to recurrent miscarriage in Taiwanese Han women.

Quantitative trait analysis suggests polymorphisms of estrogen-related genes regulate human sperm concentrations and motility.

BACKGROUND: Human spermatogenesis is regulated by complex networks, and estrogens are recognized as one of the significant regulators of spermatogenesis. We tested the associations between variants of estrogen-related genes and semen parameters. METHODS: We performed genotyping for genetic variants of estrogen-related genes and quantitative trait analysis of fertile and infertile men with well-characterized reproductive phenotypes. Men with known semen parameters (n= 677) were enrolled, including 210 fertile men and 467 infertile men. A total of 17 genetic markers from 10 genes, including 2 estrogen receptors (ER-α, ER-ß), 7 estrogen synthesizing/metabolizing genes (CYP19A1, HSD17B1, CYP1A1, CYP1B1, COMT, GSTM1, GSTT1) and 1 transport gene (SHBG) were genotyped. Sperm concentration, motility and morphology were taken as quantitative traits to correlate with genetic variants in the estrogen-related genes. RESULTS: Five genes (rs1801132 and rs2228480 of the ER-α gene, rs1256049 and rs4986938 of the ER-ß gene, rs605059 of the HSD17B1 gene, rs1799941 of the SHBG gene and rs1048943 and rs4646903 of the CYP1A1 gene) were found to be significantly associated with sperm concentration (P< 0.01), while five genes (rs1801132 of the ER-a gene, rs1256049 of the ER-ß gene, rs1048943 of the CYP1A1 gene, rs605059 of the HSD17B1 gene and rs1799941 along with rs6259 of the SHBG gene) were associated with sperm motility (P< 0.01). None of the estrogen-related genes were associated with sperm morphology. With an increasing number of risk alleles, sperm concentration and motility tended to deteriorate and show a loci-dosage effect. CONCLUSIONS: Quantitative trait analysis based on a limited number of genetic markers suggests that estrogen-related genes mainly regulate sperm concentration and motility.

Association of progesterone receptor polymorphism with idiopathic recurrent pregnancy loss in Taiwanese Han population.

PURPOSE: Recurrent pregnancy loss (RPL) could be caused by insufficient progesterone in the luteal phase of menstruation and early pregnancy. Progesterone plays a critical role in oocyte maturation, embryo implantation and placenta maintenance in early gestation. This study was set out to investigate the association between polymorphisms of the progesterone receptor (PGR) gene and idiopathic RPL. METHODS: One hundred twenty-one women with a history of idiopathic recurrent pregnancy loss (RPL) and 179 control subjects were enrolled into the study. Six tag SNPs and two functional SNPs [PROGINS (rs1042838), +331 C/T (rs10895068)] of the progesterone receptor gene were genotyped. RESULTS: We found that the allele and genotype frequencies of the functional SNP [PROGINS (rs1042838)] were both significantly higher in patients with idiopathic RPL than in the control subjects (both P values = 0.006). In addition, the C-C haplotype, which consists of rs590688C > G and rs11224592T > C, is associated with a decreased risk of RPL (p = 0.004). CONCLUSION: PROGINS polymorphism confers susceptibility to idiopathic recurrent pregnancy loss in Taiwanese Han women.

Development and validation of an expanded targeted sequencing panel for non-invasive prenatal diagnosis of sporadic skeletal dysplasia.

BACKGROUND: Skeletal dysplasia (SD) is one of the most common inherited neonatal disorders worldwide, where the recurrent pathogenic mutations in the FGFR2, FGFR3, COL1A1, COL1A2 and COL2A1 genes are frequently reported in both non-lethal and lethal SD. The traditional prenatal diagnosis of SD using ultrasonography suffers from lower accuracy and performed at latter gestational stage. Therefore, it remains in desperate need of precise and accurate prenatal diagnosis of SD in early pregnancy. With the advancements of next-generation sequencing (NGS) technology and bioinformatics analysis, it is feasible to develop a NGS-based assay to detect genetic defects in association with SD in the early pregnancy. METHODS: An ampliseq-based targeted sequencing panel was designed to cover 87 recurrent hotspots reported in 11 common dominant SD and run on both Ion Proton and NextSeq550 instruments. Thirty-six cell-free and 23 genomic DNAs were used for assay developed. Spike-in DNA prepared from standard sample harboring known mutation and normal sample were also employed to validate the established SD workflow. Overall performances of coverage, uniformity, and on-target rate, and the detecting limitations on percentage of fetal fraction and read depth were evaluated. RESULTS: The established targeted-seq workflow enables a single-tube multiplex PCR for library construction and shows high amplification efficiency and robust reproducibility on both Ion Proton and NextSeq550 platforms. The workflow reaches 100% coverage and both uniformity and on-target rate are > 96%, indicating a high quality assay. Using spike-in DNA with different percentage of known FGFR3 mutation (c.1138 G > A), the targeted-seq workflow demonstrated the ability to detect low-frequency variant of 2.5% accurately. Finally, we obtained 100% sensitivity and 100% specificity in detecting target mutations using established SD panel. CONCLUSIONS: An expanded panel for rapid and cost-effective genetic detection of SD has been developed. The established targeted-seq workflow shows high accuracy to detect both germline and low-frequency variants. In addition, the workflow is flexible to be conducted in the majority of the NGS instruments and ready for routine clinical application. Taken together, we believe the established panel provides a promising diagnostic or therapeutic strategy for prenatal genetic testing of SD in routine clinical practice.

Polymorphisms of endocrine gland-derived vascular endothelial growth factor gene and its receptor genes are associated with recurrent pregnancy loss.

BACKGROUND: Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) and its receptor genes [prokineticin receptor 1 (PKR1) and prokineticin receptor 2 (PKR2)] have been identified in the last decade and their expression is restricted to the steroidogenic glands (ovary, testis, adrenal gland and placenta). Their expression patterns also suggest a close relationship to early pregnancy. However, little information is available regarding the role of EG-VEGF and its receptors (PKR1 and PKR2) in recurrent pregnancy loss (RPL). This study was conducted to investigate the association between polymorphisms of EG-VEGF and its receptor genes (PKR1 and PKR2) and idiopathic RPL. METHODS: In this case-control study, 115 women with a history of idiopathic RPL and 170 controls were included. A total of 11 tag single nucleotide polymorphisms (SNPs) selected from EG-VEGF, PKR1 and PKR2 were genotyped. We further used multifactor dimensionality reduction (MDR) analysis to choose a best model and evaluate gene-gene interactions. RESULTS: Two tag SNPs of PKR1 (rs4627609, rs6731838) and one tag SNP of PKR2 (rs6053283) were significantly associated with idiopathic RPL (P < 0.05). The frequencies of haplotypes C-G and T-A of PKR1 and haplotype A-G-C-G-G of PKR2 were significantly increased in women with idiopathic RPL (P < 0.05); MDR tests revealed gene-gene interactions between three loci [EG-VEGF (rs7513898), PKR1(rs6731838), PKR2(rs6053283)] based on the association model (P = 0.008). The adjusted odds ratio of high- and low-risk genotype combinations in the three-locus model was 3.94 (95% confidence interval: 2.38-6.52). CONCLUSIONS: EG-VEGF receptor (PKR1, PKR2) gene polymorphisms and haplotypes were associated with idiopathic RPL. These three genes (EG-VEGF, PKR1 and PRK2) jointly contribute to RPL in the Taiwanese Han population.

Quantitative trait analysis suggests human DAZL may be involved in regulating sperm counts and motility.

A prospective study was carried out to identify the association of the DAZL (deleted in azoospermia-like) gene with major semen parameters in 210 men with normal and 467 men with abnormal semen parameters. Primer extension analysis for single nucleotide polymorphisms (SNP) of DAZL and quantitative trait analysis on the association of allele/genotype frequencies, linkage disequilibrium characteristics and DAZL haplotypes with semen parameters were investigated. Of five SNP (260A-->G, 386A-->G, 520+34c-->a, 584+28c-->t and 796+36g-->a) screened, 386A-->G was significantly correlated with sperm count (P<0.0001) and motility (P<0.005) and 584+28c-->t was marginally correlated with sperm morphology. After excluding 520+34c-->a, which was not in the Hardy-Weinberg equilibrium, the major haplotypes consisted of four SNP. One haplotype (260A-->G (major allele), 386A-->G (major allele), 584+28c-->t (minor allele) and 796+36g-->a (major allele)) was significantly associated with sperm count (P=0.003) and motility (P=0.04). This study suggests DAZL may be involved in regulating sperm counts, motility and possibly morphology.

Puerperal mastitis requiring hospitalization during a nine-year period.

OBJECTIVES: To review the clinical and microbiologic features of isolates among patients with puerperal mastitis requiring hospitalization. STUDY DESIGN: Between January 2000 and December 2008, postpartum patients who were hospitalized for mastitis were enrolled. The clinical characteristics, microbiologic results, management, and outcomes were reviewed. RESULTS: One hundred twenty-seven cases were enrolled. Seventy-six patients (59.9%) underwent incision and drainage for abscess drainage, all of whom discontinued breastfeeding. Staphylococcus aureus and coagulase-negative staphylococci were the most common isolates. Among 81 isolates of S aureus, 52 (64.2%) were resistant to oxacillin. Patients undergoing incision and drainage were more likely to discontinue breastfeeding, had a longer duration of symptoms, a longer hospitalization, a higher platelet count and higher rates of infection caused by S aureus and oxacillin-resistant S aureus. CONCLUSION: Oxacillin-resistant S aureus has emerged in patients with puerperal mastitis during the past decade, and often necessitates incision and drainage, which results in discontinuation of breastfeeding.

Novel Compound Heterozygous Mutations in CRTAP Cause Rare Autosomal Recessive Osteogenesis Imperfecta.

Whole-exome sequencing (WES) has advantages over the traditional molecular test by screening 20,000 genes simultaneously and has become an invaluable tool for genetic diagnosis in clinical practice. Here, we reported a family with a child and a fetus presenting undiagnosed skeletal dysplasia phenotypes, while the parents were asymptomatic. WES was applied to the parents and affected fetus to identify the genetic cause of the phenotypes. We identified novel compound heterozygous mutations consisting of a single-nucleotide variant (SNV) and a large deletion in the CRTAP gene (NM_006371.4:c.1153-3C > G/hg19 chr3:g.32398837_34210906del). Genetic alterations of CRTAP are known to cause osteogenesis imperfecta (OI) in an autosomal recessive manner. Further examination of the proband's elder sibling who was diagnosed as OI after birth found that she shares the inherited compound heterozygous mutations of CRTAP; thus, the findings support the disease-causing role of CRTAP mutations. Through the in vitro molecular test and in silico analysis, the deleterious effects of the splicing-altering SNV in CRTAP (c.1153-3C > G) on gene product were confirmed. Collectively, our WES-based pathogenic variant discovery pipeline identifies the SNVs and copy number variation to delineate the genetic cause on the proband affected with OI. The data not only extend the knowledge of mutation spectrum in patients with skeletal dysplasia but also demonstrate that WES holds great promise for genetic screening of rare diseases in clinical settings.

Triple genetic identities for the complete hydatidiform mole, placenta and co-existing fetus after transfer of a single in vitro fertilized oocyte: case report and possible mechanisms.

We found different genotypes for the complete hydatidiform mole (CHM), placenta and co-existing fetus derived from a single in vitro fertilized human oocyte by the analysis of short tandem repeat (STR) DNA markers. The molar tissue was found to be heterozygously androgenetic. The fetus and placenta contained identical maternal, but different paternal genomes. Two models were proposed to account for the identification of triple genetic identities in a single fertilized oocyte. In the first model, the oocyte was fertilized by a diploid sperm, resulting in diandric triploidy. Premature cytokinesis resulted in early splitting of a cytoplasmic fragment with one copy of the replicated sperm chromosome, which developed into a heterozygous CHM. The bipolar spindle in syngamy pulled the other copy of sperm chromosomes and replicated oocyte chromosomes to form two blastomeres, which develop into the fetus and placenta, respectively. In the second model, the oocyte was fertilized by two haploid sperms, followed by tripolar spindle formation. Whatever is the mechanism, this case provides direct evidence that CHM can be derived from an oocyte containing an intact maternal genome.

Moxifloxacin-associated neutropenia in a cirrhotic elderly woman with lower extremity cellulitis.

OBJECTIVE: To report a case of moxifloxacin-associated neutropenia in a cirrhotic patient with cellulitis. CASE SUMMARY: A 77-year-old cirrhotic woman developed cellulitis of the right leg, with a nadir white blood cell (WBC) count of 1.5 x 10(3)/microL and absolute neutrophil count (ANC) of 0.345 x 10(3)/microL, which occurred after 5 days of moxifloxacin therapy. Moxifloxacin was switched to cefixime and neutropenia resolved 2 days after the withdrawal of moxifloxacin. DISCUSSION: Cases of neutropenia related to fluoroquinolones have rarely been reported in the literature, and neutropenia associated with moxifloxacin has not been described before. Because of the temporal relationship between moxifloxacin administration and the development of neutropenia in our patient, as well as the relationship between drug withdrawal and improvement in WBC count and ANC, moxifloxacin-associated neutropenia was suspected. This reaction was categorized as probable according to the Naranjo probability scale. CONCLUSIONS: We report the first case of moxifloxacin-associated neutropenia. Although such an adverse reaction is rare, clinicians should be aware of this potential complication of moxifloxacin therapy.

Association of USP26 haplotypes in men in Taiwan, China with severe spermatogenic defect.

AIM: To complete comprehensive haplotype analysis of USP26 for both fertile and infertile men. METHODS: Two hundred infertile men with severe oligospermia or non-obstructive azoospermia were subjected to sequence analysis for the entire coding sequences of the USP26 gene. Two hundred men with proven fertility were genotyped by primer extension methods. Allele/genotype frequencies, linkage disequilibrium (LD) characteristics and haplotypes of fertile men were compared with infertile men. RESULTS: The allele frequencies of five single nucleotide polymorphisms (370-371insACA, 494T>C, 576G>A, ss6202791C>T, 1737G>A) were significantly higher in infertile patients than control subjects. The major haplotypes in infertile men were TACCGA (28% of the population), TGCCGA (15%), TACCAA (8%), TGCCAA (6%), TATCAA (5%) and CATCAA (5%). The major haplotypes for the control subjects were TACCGA (58% of the population), CACCGA (7%), CATCGA (6%) and TGCCGA (5%). Haplotypes TGCCGA, TATCAA, CATCAA, CATCGC, TACCAA and TGCCAA were over-transmitted in patients with spermatogenic defect, whereas haplotypes TACCGA, CACCGA, and CATCGA were under-transmitted in these patients. CONCLUSION: Some USP26 alleles and haplotypes are associated with spermatogenic defect in the Han nationality in Taiwan, China.

Cefotaxime-ciprofloxacin combination therapy for nontyphoid Salmonella bacteremia and paravertebral abscess after failure of monotherapy.

Therapeutic failure of monotherapy with either a third-generation cephalosporin or a fluoroquinolone against nontyphoid salmonellae has been observed in clinical practice. Combination therapy with both agents is recommended in the literature for treating life-threatening infections. However, we know of no published case reports that indicate a therapeutic advantage of this combination therapy for nontyphoid salmonellae infections. We describe a 60-year-old man who had breakthrough bacteremia with vertebral osteomyelitis and paravertebral abscess caused by Salmonella enterica serotype Choleraesuis. This was not controlled with sequential monotherapy but was eventually cured with cefotaxime-ciprofloxacin combination therapy. The Etest showed that the strain was susceptible to cefotaxime and ciprofloxacin, but resistant to nalidixic acid. Cefotaxime and ciprofloxacin in combination may be considered as an option for difficult-to-treat salmonellosis.

Delayed uterine rupture occurred 4 weeks after cesarean section following sexual intercourse: a case report and literature review.

OBJECTIVE: Spontaneous delayed uterine rupture is life-threatening and extremely rare following sexual intercourse in postpartum. Here, we present a case of delayed uterine rupture that occurred 4 weeks after cesarean section following intercourse. CASE REPORT: A 31-year-old postpartum woman, gravida 4, para 1, abortion 3, underwent a cesarean section for prolonged labor. She was transferred to our hospital in shock status with brisk vaginal bleeding following intercourse 4 weeks after delivery. An emergency subtotal hysterectomy was performed to stop the bleeding. The pathology confirmed tissue necrosis and suture granuloma at the previous surgical wound. CONCLUSION: The presented case demonstrated that delayed uterine rupture may occur even 4 weeks after delivery following intercourse, without any obvious abdominal pain or infection signs, which deserved the attention of obstetricians.

Human sex ratio at amniocentesis and at birth in Taiwan.

OBJECTIVES: An increase in the proportion of male-to-female live births has raised concerns in Taiwan. Disclosure of fetal sex during prenatal screening is not allowed by the Taiwan government. Fetal sex annotation in clinical genetic reports is also prohibited. This study tested the hypothesis that the male-to-female sex ratio at amniocentesis should be lower than the sex ratio at birth, if a certain percentage of female fetuses are being selectively aborted after amniocentesis. Therefore, we examined the differences between fetal sex ratio at amniocentesis at a tertiary medical center in southern Taiwan and the nationwide sex ratio at birth in Taiwan from 1992 to 2011. MATERIALS AND METHODS: Data of normal male and female karyotypes during the study period were collected from the cytogenetic laboratory of the National Cheng Kung University Hospital (NCKUH) in southern Taiwan. Data of sex ratio at birth nationwide in Taiwan were obtained from the Department of Statistics, Ministry of the Interior, Taiwan. We calculated 95% binominal confidence intervals for the sex ratios and differences between fetal sex ratio at amniocentesis, and nationwide sex ratio at birth were tested by the χ(2) test and Bonferroni correction. RESULTS: The nationwide sex ratio at birth ranged from 1.07 to 1.11 during the period from 1992 to 2011 in Taiwan, with the highest in 2004 and the lowest in 1993. The fetal sex ratio at amniocentesis at NCKUH ranged more widely (0.82-1.28), with the lowest in 1993 and the highest in 2007. After regression analysis, both trends of sex ratio at amniocentesis during midtrimester and at birth were not significantly increased by years. Furthermore, the sex distribution at amniocentesis during midtrimester did not differ significantly from the nationwide sex ratio at birth (1.113 vs. 1.092, p = 0.151). CONCLUSIONS: The results showed that sex ratio was already skewed toward male at midtrimester. Our data imply that artificial sex selection, if it were present, might have already emerged prior to the timing of amniocentesis. However, more large nationwide studies on sex ratios in Taiwan are warranted.

Complex chromosome rearrangement 46,XY, der(9)t(Y;9)(q12;p23) in a girl with sex reversal and mental retardation.

Monosomy 9p syndrome, also known as Alfi syndrome, has been described as a contiguous syndrome characterized by mental retardation, developmental delay, and facial dysmorphisms. Males with monosomy 9p often express variable degrees of feminization, although the genitalia of females will be normal. In the present report, we describe a case of ambiguous genitalia and intra-abdominal testicular development, with a derivative chromosome 9 arising from a translocation between 9p23 and Yq heterochromatin. Pathologic examination of the testes showed germ cell hypoplasia of the seminiferous tubules. fluorescence in situ hybridization, spectral karyotyping, and array comparative genomic hybridization were used to characterize the genetic changes.

Gestational diabetes and central pontine myelinolysis with quadriplegia: a case report.

Central pontine myelinolysis (CPM) has been reported in women with severe hyperemesis gravidarum-induced hyponatremia followed by rapid correction. Gestational diabetes with adipsia complicated by acute hypernatremia resulting in CPM has never been reported. Here is a case of a disabled female who presented with polydipsia, polyuria, seizures, fetal death in utero, hyperglycemia, and hyper-osmolar hypernatremia on her 31st gestational week. The dead fetus was delivered and the patient's plasma glucose and sodium were later stabilized. When the patient developed quadriplegia and respiratory failure 5 days later, brain magnetic resonance imaging showed central pontine and extra-pontine myelinolysis. Gestational diabetes complicated by hyper-osmolar crisis may cause fetal death and severe neurologic sequela. Early recognition and delivery of the fetus and placenta may improve the electrolyte and fluid imbalance.

Polymorphisms of estrogen-related genes jointly confer susceptibility to human spermatogenic defect.

OBJECTIVE: To establish a multilocus model for studying the effect of estrogen-related genes on impaired spermatogenesis. DESIGN: Prospective study. SETTING: University-based reproductive clinics and genetics laboratory. PATIENT(S): A total of 183 oligozoospermatic (sperm count <20 x 10(6)/mL) or azoospermatic males and 120 fertile control males were included. INTERVENTION(S): A total of 16 single nucleotide polymorphisms (SNPs) from nine genes (estrogen receptors [ER-alpha, ER-beta], estrogen synthesizing/metabolizing genes [CYP17, CYP19A1, HSD17B2, CYP1A1, CYP1B1, COMT], and transport genes [SHBG]) were genotyped. The combinatorial effect of multiple genetic variants was assessed using the multilocus model. MAIN OUTCOME MEASURE(S): Significantly associated SNPs and odds ratio (OR). RESULT(S): Six SNPs from five genes (rs180113 of ER-alpha gene, rs1256049 of ER-beta gene, rs1048943 of CYP1A1 gene, rs8191246 of HSD17B2 gene, and rs1799941 along with rs6259 of SHBG gene) were found to be significantly associated with spermatogenic defect. The genes were further divided into three categories according to their functions (receptors, synthesis and metabolism, and transporter). Based on our multilocus risk model, men with risk alleles in two of the three gene families had increased risk of impaired sperm production (OR = 10.5). The OR further increased to 34.6 for men with unfavorable alleles for all three gene families. CONCLUSION(S): Polymorphisms of estrogen-related genes jointly confer susceptibility to human spermatogenic defect at the prereceptor, receptor, and postreceptor levels in the Taiwanese Han population.

Maternal derivative chromosome 9 and recurrent pregnancy loss.

OBJECTIVE: To disclose the relationship between a derivative chromosome 9 and recurrent pregnancy loss. DESIGN: Case report. SETTING: Referral from primary clinical care to tertiary hospital for further intervention. PATIENT(S): A 31-year-old woman who had four recurrent early spontaneous abortions. INTERVENTION(S): Cytogenetic and fluorescence in situ hybridization analyses of the chromosome harvested from peripheral blood sample. MAIN OUTCOME MEASURE(S): Karyotype of the patient. RESULT(S): The patient has a unique derivative chromosome 9, der(9)(9qter-->9p24::9p24-->9p11::9p13-->9qter). ish der(9) (CEP9x1,43N6x1,D9Z3x1). CONCLUSION(S): Maternal derivative chromosome 9 may cause recurrent pregnancy loss.