An unusual case of severe asphyxia with the fetal position unexpectedly inverted in a malformed uterus: a case report.

BACKGROUND: We present a severe neonatal consequence due to the unexpected and crucial inversion of the fetal position after sudden termination of tocolysis during early labor of a woman with congenital uterine anomaly. It has been reported that congenital uterine anomalies latently affect the fetal position. The clinical pitfalls in childbirth with uterine anomalies are discussed here on the basis of clinical evidence. CASE PRESENTATION: At a perinatal medical center in Japan, a 29-year-old Japanese mother who had a history of bicornuate uterus, received tocolysis to prolong her pregnancy for 5 days during the late preterm period after preterm-premature rupture of the membrane. She gave birth to a 2304 g male neonate of the gestational age of 35 weeks and 5 days with severe asphyxia by means of crash cesarean section for fetal sustained bradycardia after sudden termination of tocolysis. We found the fetal position to reverse from cephalic to breech position during early labor. He ended up having severe cerebral palsy after brain cooling against hypoxic-ischemic encephalopathy for 3 days. The mechanism of inversion from cephalic to breech position without amnionic fluid remains unclear, although women with a known diagnosis of a uterine anomaly have higher risk of adverse outcomes such as malpresentation. CONCLUSIONS: When considering the clinical course of this case on the basis of the medical reports, we suspected that uterine anomalies and changes in intrauterine pressure could cause fetal malpresentation and adverse neonatal outcomes.

A novel mutation in TAZ causes mitochondrial respiratory chain disorder without cardiomyopathy.

Tafazzin, encoded by the TAZ gene, is a mitochondrial membrane-associated protein that remodels cardiolipin (CL), an important mitochondrial phospholipid. TAZ mutations are associated with Barth syndrome (BTHS). BTHS is an X-linked multisystemic disorder affecting usually male patients. Through sequence analysis of TAZ, we found one novel mutation c.39_60del p.(Pro14Alafs*19) by whole-exome sequencing and a reported missense mutation c.280C>T p.(Arg94Cys) by Sanger sequencing in two male patients (Pt1 and Pt2). Patient with c.280C>T mutation had dilated cardiomyopathy, while another patient with c.39_60del mutation had no feature of cardiomyopathy. A reported m.1555A>G homoplasmic variant was also identified in the patient having mutation c.39_60del by whole mitochondrial DNA sequencing method. This variant was not considered to be the main cause of mitochondrial dysfunction based on a cytoplasmic hybrid (cybrid) assay. Tafazzin expression was absent in both patient-derived fibroblast cells. Complementation of TAZ expression in fibroblasts from the patient with the novel mutation c.39_60del restored mitochondrial respiratory complex assembly. High-performance liquid chromatography-tandem mass spectrometry-based metabolic analysis revealed the decline of CL and the accumulation of monolysocardiolipin, indicating the loss of tafazzin activity. Owing to phenotypic variability, it is difficult to diagnose BTHS based on clinical features only. We conclude that genetic analysis should be performed to avoid underdiagnosis of this potentially life-threatening inborn error of metabolism.

Orotate phosphoribosyltransferase localizes to the Golgi complex and its expression levels affect the sensitivity to anti-cancer drug 5-fluorouracil.

Orotate phosphoribosyltransferase (OPRT) is engaged in de novo pyrimidine synthesis. It catalyzes oronitine to uridine monophosphate (UMP), which is used for RNA synthesis. De novo pyrimidine synthesis has long been known to play an important role in providing DNA/RNA precursors for rapid proliferative activity of cancer cells. Furthermore, chemotherapeutic drug 5-fluorouracil (5-FU) is taken up into cancer cells and is converted to 5-fluoro-UMP (FUMP) by OPRT or to 5-fluoro-dUMP (FdUMP) through intermediary molecules by thymidine phosphorylase. These 5-FU metabolites are misincorporated into DNA/RNA, thereby producing dysfunction of these information processing. However, it remains unclear how the subcellular localization of OPRT and how its variable expression levels affect the response to 5-FU at the cellular level. In this study, immunocytochemical analysis reveals that OPRT localizes to the Golgi complex. Results also show that not only overexpression but also downregulation of OPRT render cells susceptible to 5-FU exposure, but it has no effect on DNA damaging agent doxorubicin. This study provides clues to elucidate the cellular response to 5-FU chemotherapy in relation to the OPRT expression level.

Newborn hypocarnitinemia due to long-term transplacental pivalic acid passage.

Infants often develop hypocarnitinemia and resultant hypoglycemia during long-term treatment with antibiotics that contain pivalic acid, but it is unknown whether maternal treatment with such agents during pregnancy induces hypocarnitinemia in fetuses or neonates. A woman at week 28 of pregnancy was prescribed cefcapene pivoxil for 84 consecutive days for treatment and prophylaxis of pyelonephritis. Using tandem mass spectrometry, both the mother and newborn were found to have hypocarnitinemia soon after delivery. It was concluded that the baby suffered from secondary hypocarnitinemia due to long-term prenatal treatment with antibiotics containing pivalic acid. Long-term treatment with antibiotics containing pivalic acid in pregnant women can induce hypocarnitinemia in both the mother and neonate; reported herein is the first case observed in humans.

[A case of laryngeal adenosquamous carcinoma].

We report a rare case of adenosquamous carcinoma of the larynx. A 38-year-old man with a 9-month history of progressive hoarseness and dyspnea during exercise and sudden-onset breathing difficulty was unable to be intubated and underwent a tracheostomy at the emergency department. He was found in endoscopic examination of the larynx to have a large smooth subglottic mass with laryngeal stenosis. The bilateral vocal cords were fixed. No cervical lymph node was seen. Excisional laryngofissure biopsy led to a pathological diagnosis of adenosquamous carcinoma, necessitating laryngectomy with bilateral neck dissection (Level II-IV) and postoperative radiation therapy. He died of metastatic disease 7.5 years after the initial treatment, without locoregional recurrence. Among malignant laryngeal tumors, adenosquamous carcinoma is extremely rare, with only 33 such cases including ours reported in the literature.

[Clinical evaluation of the effect of tamsulosin hydrochloride and cernitin pollen extract on urinary disturbance associated with benign prostatic hyperplasia in a multicentered study].

We evaluated the clinical efficacy and safety of tamsulosin hydrochloride and cernitin pollen extract in 243 patients with urinary disturbance associated with benign prostatic hyperplasia. They were assigned randomly to 3 groups, oral tamsulosin hydrochloride, cernitin pollen extract and their combination were administered for 12 weeks. The international prostate symptom score, post-voided residual urine and uroflowmetrogram were obtained before and after treatment. The international prostate symptom score improved in each group and then the maximum flow rate and average flow rate also increased significantly in the tamsulosin hydrochloride-administered groups. In conclusion, the administration of only tamsulosin hydrochloride and the combination of tamsulosin hydrochloride and cernitin pollen extract seemed more effective then the administration of only cernitin pollen extract in the treatment of urinary disturbance associated with benign prostatic hyperplasia.