Global issues in obstetric anaesthesia: perspectives from South Africa, Japan, China, Latin America and North America.

South Africa is classified as a low- and middle-income country, with a complex mixture of resource-rich and resource-limited settings. In the major referral hospitals, the necessary skill level exists for the management of complex challenges. However, this contrasts with the frequently-inadequate skill levels of anaesthesia practitioners in resource-limited environments. In Japan, obstetricians administer anaesthesia for 40% of caesarean deliveries and 80% of labour analgesia. Centralisation of delivery facilities is now occurring and it is expected that obstetric anaesthesiologists will be available 24 h a day in centralised facilities in the future. In China, improvements in women's reproductive, maternal, neonatal, child, and adolescent health are critical government policies. Obstetric anaesthesia, especially labour analgesia, has received unprecedented attention. Chinese obstetric anaesthesiologists are passionate about clinical research, focusing on efficacy, safety, and topical issues. The Latin-American region has different landscapes, people, languages, and cultures, and is one of the world's regions with the most inequality. There are large gaps in research, knowledge, and health services, and the World Federation of Societies of Anaesthesiologists is committed to working with governmental and non-governmental organisations to improve patient care and access to safe anaesthesia. Anaesthesia workforce challenges, exacerbated by coronavirus disease 2019, beset North American healthcare. Pre-existing struggles by governments and decision-makers to improve health care access remain, partly due to unfamiliarity with the role of the anaesthesiologist. In addition to weaknesses in work environments and dated standards of work culture, the work-life balance demanded by new generations of anaesthesiologists must be acknowledged.

Optimisation of antithrombin resistance assay as a practical clinical laboratory test: Development of prothrombin activator using factors Xa/Va and automation of assay.

INTRODUCTION: Antithrombin resistance (ATR) is a novel thrombotic risk in abnormal prothrombins. A manual ATR assay using Oxyuranus scutellatus (Ox) venom as a prothrombin activator was established for detecting antithrombin-resistant prothrombin. However, this assay was limited because of Ox snake venom availability and its throughput capacity. Here, we have improved the ATR assay using bovine factors Xa and Va (FXa/Va) as prothrombin activators and have optimised assay conditions for an automated instrument (ACL TOP 500). METHODS: Diluted plasma was incubated with a prothrombin activator mix (phospholipids, CaCl2 , and bovine FXa/Va), followed by inactivation with antithrombin for 10, 20 and 30 minutes. We added a chromogenic substrate S-2238, and assessed changes in absorbance/min at 405 nm. We also adapted assay conditions for ACL TOP 500. RESULTS: Optimum conditions for FXa/Va treatment were 6.25% phospholipids, 5 mM CaCL2 , 0.01 µg/mL FXa and 0.1 µg/mL FVa. ATR assay kinetics with the FXa/Va activator was comparable with that with the Ox activator in heterozygous reconstituted plasma with the recombinant wild-type or antithrombin-resistant prothrombin. Using ACL TOP 500, optimum conditions for the FXa/Va treatment were 10.0% phospholipids, 5 mM CaCl2 , 0.02 µg/mL FXa and 0.2 µg/mL FVa. The automated ATR assay with the FXa/Va activator demonstrated good detectability for antithrombin-resistant prothrombin in plasma from a heterozygous carrier with prothrombin Yukuhashi or Belgrade. CONCLUSION: We optimised the ATR assay with the FXa/Va activator and adapted the assay for ACL TOP 500; the assay showed the ability to clearly detect antithrombin-resistant prothrombin in manual and automated procedures.

Determinants of Awareness and Practice of Breast Self Examination Among Rural Women in Trichy, Tamil Nadu.

INTRODUCTION: Breast cancer is the most common cancer among women worldwide, and it can be detected at an early stage through self-examination which increases the chance of survival. This study aimed to assess knowledge and practice of breast self-examination (BSE) among females in a rural area of Trichy district. METHODOLOGY: This community-based, cross-sectional study was carried out among a total sample of 200 women in rural area of Trichy. The participants were interviewed using a structured interviewer-administered questionnaire to obtain information on their sociodemographic characteristics, awareness on breast cancer, and knowledge, attitude, practice of BSE. Data were entered into MS Excel and analyzed using SPSS version 20.0. Spearman correlation and Chi-square test were used to analyze the association between the variables. RESULTS: The mean age of the study group was 36.9 ± 8.8 years. Eighty percent were literates. Most of the women 178 (89%) were aware of breast cancer. Only 26% of the women were aware of BSE. Only 18% of the females had ever checked their breast and 5% practiced it regularly. Awareness of BSE was found to be significantly associated with age and educational attainment. CONCLUSION: The level of knowledge and practice of BSE among females are unacceptably low. Efforts should be made to increase level of knowledge and practice of BSE through health education programs.

Assessing Blood Flow in an Intracranial Stent: A Feasibility Study of MR Angiography Using a Silent Scan after Stent-Assisted Coil Embolization for Anterior Circulation Aneurysms.

BACKGROUND AND PURPOSE: Blood flow in an intracranial stent cannot be visualized with 3D time-of-flight MR angiography owing to magnetic susceptibility and radiofrequency shielding. As a novel follow-up tool after stent-assisted coil embolization, we applied MRA by using a Silent Scan algorithm that contains an ultrashort TE combined with an arterial spin-labeling technique (Silent MRA). The purpose of this study was to determine whether Silent MRA could visualize flow in an intracranial stent placed in the anterior circulation. MATERIALS AND METHODS: Nine patients treated with stent-assisted coil embolization for anterior circulation aneurysms underwent MRAs (Silent MRA and TOF MRA) and x-ray digital subtraction angiography. MRAs were performed in the same session on a 3T unit. Two neuroradiologists independently reviewed the MRA images and subjectively scored flow in a stent as 1 (not visible) to 4 (excellent) by referring to the latest x-ray digital subtraction angiography image as a criterion standard. RESULTS: Both observers gave MRA higher scores than TOF MRA for flow in a stent in all cases. The mean score for Silent MRA was 3.44 ± 0.53, and for TOF MRA, it was 1.44 ± 0.46 (P < .001). CONCLUSIONS: Silent MRA was able to visualize flow in an intracranial stent more effectively than TOF MRA. Silent MRA might be useful for follow-up imaging after stent-assisted coil embolization, though these study results may be only preliminary due to some limitations.

[Sjögren-Larsson syndrome: a novel mutation in a Moroccan child]. / Syndrome de Sjögren-Larsson en rapport avec une nouvelle mutation chez un enfant marocain.

Sjögren-Larsson syndrome is a very rare inherited neurocutaneous disorder caused by a deficiency of microsomal enzyme fatty aldehyde dehydrogenase (FALDH). The authors report a case of typical Sjögren-Larsson syndrome in a 7-year-old Moroccan child who presented with classical symptoms (congenital ichthyosis, mental retardation, and spastic paraparesis) and epilepsy. The genetic study revealed a new mutation in the FALDH gene mapped to chromosome 17, consisting in a G109A substitution in exon 2.

Proteomic analysis of stage I primary lung adenocarcinoma aimed at individualisation of postoperative therapy.

Although postoperative adjuvant chemotherapy (PAC) with uracil-tegafur significantly improves the prognosis of patients with stage I lung adenocarcinoma, subset analysis has revealed that only 11.5% of patients with stage IB derive actual benefit from such therapy. Therefore, it is extremely important to identify patients for whom adjuvant chemotherapy will be beneficial. We performed comprehensive protein analysis of 24 surgically resected specimens of stage I adenocarcinoma using liquid chromatography-tandem mass spectrometry (LC-MS/MS), followed by bioinformatical investigations to identify protein molecules. Furthermore, we carried out immunohistochemical studies of 90 adenocarcinoma specimens to validate the results of LC-MS/MS. We detected two kinds of protein molecules (myosin IIA and vimentin) by LC-MS/MS. We confirmed their immunohistochemical expression and distribution, and evaluated the relationship between the expression of these proteins and prognosis after adjuvant chemotherapy. Patients with no expression of either myosin IIA or vimentin showed a significantly better outcome regardless of PAC using uracil-tegafur. However, we were unable to select responders to uracil-tegafur using these proteins. Cases of adenocarcinoma lacking expression of either myosin IIA or vimentin show a good outcome without PAC, and therefore do not require such treatment.

Breast cancer resistance protein (BCRP) affected acquired resistance to gefitinib in a "never-smoked" female patient with advanced non-small cell lung cancer.

Development of acquired resistance to gefitinib after an initial good response is common. Recently, it was reported that this acquired resistance is related to a secondary mutation associated with a substitution of threonine by methionine at codon 790 (T790M) of the epidermal growth factor receptor (EGFR) gene. In this report, we present a "never smoking" woman with advanced lung cancer who showed acquired resistance to gefitinib, and analysis of autopsy samples revealed no evidence of EGFR mutations in either exons 18-21 or codon 790, and positive immunostaining for breast cancer resistance protein (BCRP). We describe, for the first time, a case in which expression of BCRP was associated with acquired resistance to gefitinib, independent of EGFR mutations.

A case of a Japanese neonate with congenital ichthyosiform erythroderma diagnosed as Netherton syndrome.

We report a 6-day-old Japanese girl showing generalized erythroderma accompanied by yellowish, exfoliative scaling that was accentuated on the face and scalp. Histological analysis showed psoriasiform dermatitis with acanthotic epidermis and premature shedding of the stratum corneum. Measurement of trypsin-like hydrolytic activity in SC showed six-fold greater activity compared with age-matched controls. DNA analysis revealed two mutations, 375delAT and 966insC, in exons 5 and 11, respectively, of the SPINK5 gene. Although at 4 weeks the child was still too young to display characteristic hair abnormalities or atopic diathesis, we diagnosed Netherton syndrome based on enzyme assay and DNA analysis.

Basic and clinical research on photodynamic therapy at Tokyo Medical University Hospital.

BACKGROUND AND OBJECTIVES: We have been engaged in basic and clinical research on photodynamic therapy (PDT) and photodynamic diagnosis (PDD) for more than 25 years. STUDY DESIGN/MATERIALS AND METHODS: PDT for 264 centrally located early-stage lung cancer lesions yielded an initial complete response (CR) rate of 84.8%. PDT is now becoming a standard option for centrally located stage 0 (TisN0M0) and stage I (T1N0M0) lung cancer. It is an attractive option for elderly patients in poor physical condition. RESULTS: Recent results of interstitial PDT for peripheral-type lung cancers suggest that it may be a promising local curative treatment modality for lesions less than 1.0 cm in diameter. CONCLUSIONS: In this article, we introduce our recent clinical trials of PDT for lung cancers (both central and peripheral), and new techniques of PDD in sentinel node navigation biopsy for breast cancers. Moreover, we introduce basic research on cancers and infectious diseases in order to expand the clinical applications of PDT.

A Japanese infant with localized ichthyosis linearis circumflexa on the palms and soles harbouring a compound heterozygous mutation in the SPINK5 gene.

We report a 6-month-old Japanese boy showing ichthyosis linearis circumflexa localized on the palms and soles. He showed bamboo hairs and aminoaciduria, and was positive for cow's milk and egg IgE antibodies by radioallergosorbent tests. Trypsin-like hydrolytic activity in the patient's lesional stratum corneum showed an activity seven times higher than that in age-matched controls. DNA analysis showed that the patient harboured the compound heterozygous mutations R790X and 1220+1 G-->C in the SPINK5 gene, compatible with the diagnosis of Netherton syndrome (NS). As the genotype/phenotype correlations in NS have not yet been fully clarified, the position of the premature termination codon in the SPINK5 gene may contribute to explain such a mild form of NS in our patient.

Beneficial effect of JTV-803, a new synthetic inhibitor of activated factor X, against both lipopolysaccharide-induced and tissue factor-induced disseminated intravascular coagulation in rat models.

We examined whether JTV-803, a specific activated factor X inhibitor independent of antithrombin III (ATIII), is effective against disseminated intravascular coagulation (DIC) in rat models induced by tissue factor (TF) or lipopolysaccharides (LPS). In male Wistar rats, DIC was induced by a 4 h infusion of thromboplastin (3.75 U/kg) or LPS (50 mg/kg). The rats were given JTV-803 (0.3 or 3 mg/kg, bolus intravenously) (JTV-803 groups) or low molecular weight heparin (LMWH groups) (200 U/kg, bolus intravenously) prior to an injection of TF or LPS. The results showed that JTV-803 was dose-dependently effective against DIC in both TF-induced and LPS-induced rat models. This anti-DIC effect of JTV-803 at higher doses was almost equivalent to that of LMWH in both types of DIC. Plasma ATIII activity was more prominent in the group treated with JTV-803 than in that treated with LMWH. None of rats died in the TF-induced DIC model with or without drug administration. On the contrary, seven of 22 rats died (mortality rate, 31.8%) in the LPS-induced DIC model without drug administration. Although the mortality rate of rats induced with LPS and treated with LMWH was quite high (6/16, 37.5%), none of the LPS-induced rats treated with JTV-803 died. These findings suggested that JTV-803 can treat both TF-induced and LPS-induced DIC models, and that this drug has greater potential in preserving ATIII and in improving the prognosis of DIC.