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2017; 66: 678 - 85. 3 Iijima S, Matunaga K. A case of allergic contact dermatitis caused by Olanedine solution-a diagnostic patch-testing method involving dried filter paper. Dear Editor, Olanexidine gluconate (Olanedine®, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan) is a relatively new biguanide antiseptic solution released in 2015 and now available in Japan. The histopathology of erythema on her thigh revealed acanthosis and dyskeratosis, with mild spongiosis, along with perivascular lymphocytic infiltrates in the dermis (Figure 2a,b). [Extracted from the article]

Antigen-stimulated naïve T cells differentiate into effector and memory T cells, of which resident memory T (T RM) cells reside permanently in organ tissues. Involvement of T RM cells has been indicated in pathological conditions of various skin diseases. CD122, which is the β chain subunit of interleukin (IL)− 2 and IL-15 receptors, is expressed on immune cells including T RM cells. To investigate whether CD122 signaling in skin CD8+ T RM cells mediates the development of mucocutaneous graft-versus-host disease (GVHD). We used a genetically modified mouse expressing a membrane-bound form of chicken ovalbumin (OVA) under the control of the keratin 14 promoter, which develops GVHD-like erosive mucocutaneous disease resulting in sclerodermatous disease after transfer of OVA-specific T cell-receptor-transgenic CD8+ OT-I cells. Mice with mucocutaneous GVHD were treated with an anti-CD122 blocking antibody. Administration of an anti-CD122 blocking antibody suppresses the development of acute/chronic GVHD-like mucocutaneous disease in our murine model via the reduction of CD122-expressing memory CD8+ T cells, including skin, memory autoaggressive CD8+ T cells. Moreover, blockade of CD122, even after the establishment of acute GVHD, inhibited the development of chronic GVHD-like sclerodermatous disease via the reduction of epidermal and dermal T RM autoaggressive CD8+ T cells. Skin memory CD8+ T cells in particular mediate the development of mucocutaneous GVHD, and blockade of CD122 may be an effective treatment strategy, especially for sclerodermatous GVHD. • Resident memory T cells involve in pathological conditions of various skin diseases. • Anti-CD122 antibody treatment specifically decreases skin resident memory T cells. • Blockade of CD122 is therapeutic for sclerodermatous graft-versus-host disease. [ABSTRACT FROM AUTHOR]

Multiple system atrophy (MSA) is a rare neurodegenerative disease characterized by parkinsonism, cerebellar impairment, and autonomic failure. Although the causes of MSA onset and progression remain uncertain, its pathogenesis may involve oxidative stress via the generation of excess reactive oxygen species and/or destruction of the antioxidant system. One of the most powerful antioxidants is glutathione, which plays essential roles as an antioxidant enzyme cofactor, cysteine-storage molecule, major redox buffer, and neuromodulator, in addition to being a key antioxidant in the central nervous system. Glutathione levels are known to be reduced in neurodegenerative diseases. In addition, genes regulating redox states have been shown to be post-transcriptionally modified by microRNA (miRNA), one of the most important types of non-coding RNA. miRNAs have been reported to be dysregulated in several diseases, including MSA. In this review, we focused on the relation between glutathione deficiency, miRNA dysregulation and oxidative stress and their close relation with MSA pathology. [ABSTRACT FROM AUTHOR]

Bacillus cereus is known to cause two types of food poisoning: emetic and diarrhoeal. Both diseases are usually self-limiting; however, severe cases have been reported, presenting with acute liver failure and encephalopathy, including rarely fatal cases of vomiting. Clinical laboratories do not routinely test for B. cereus in patients with gastrointestinal disease. Therefore, B. cereus causing food poisoning goes undetected. We report a successful isolation of emetic B. cereus from a patient with food poisoning who presented with severe vomiting, fulminant hepatic failure, and acute encephalopathy, by a non-conventional method. Initially, stool specimens from the patients were routinely cultured to identify the causative organisms of food poisoning. No foodborne pathogens were detected in this study. In contrast, additional clinical and epidemiological information strongly suggested food poisoning by emetic B. cereus. Consequently, we allowed Drigalski agar medium smeared with patient stool specimens to stand at room temperature (approximately 25 °C) for 9 days. After 9 days, mixed bacteria grown on the medium were inoculated onto mannitol egg yolk polymyxin (MYP) agar plates, a selective medium for B. cereus. Typical colonies of B. cereus developed on MYP agar plates. The isolated B. cereus had a cereulide-producing genetic locus (ces) gene encoding the emetic toxin cereulide. The method used in this case study was unique. This method is easy to apply after obtaining an additional clinical and epidemiological information, and this method will improve the diagnostic rate of severe B. cereus food poisoning. This will contribute to the advancement of therapeutics in the future. [ABSTRACT FROM AUTHOR]

Immunoglobulin A vasculitis (IgAV) is a type of vasculitis affecting small vessels with deposition of immune complexes consisting of IgA and complement component 3. IgAV involves the skin, gastrointestinal (GI) tract, joints, and kidneys. Adult patients have higher risks of gastrointestinal tract involvement than children. To investigate the risk factors of the GI tract involvements in adult IgAV patients, we enrolled 29 adult (aged ≥ 20 years) Japanese patients recently (from 2013 to 2019) histopathologically diagnosed with IgAV and classified them into the GI lesion (+) group and the GI lesion (−) group. All patients presented with purpura on the lower extremities; moreover, GI lesion (+) patients presented significantly more with extensive purpura on the upper extremities, and low levels of factor XIII activity (≤70%) than gastrointestinal lesion (−) patients (87.5% vs 28.6% [P =.004]; odds ratio [OR], 17.5; 95% confidence interval [CI], 2.4 to 366], and 57.1% vs 14.3% [P =.04]; OR, 8; 95% CI, 1.06 to 83.9, respectively). There was no significant difference between the two groups in the populations with extensive purpura on the trunk, arthralgia, hematuria, proteinuria, or elevated serum levels of C‐reactive protein or IgA. Widespread purpura on the upper extremities accompanied by a low factor XIII activity is a suggestive factor for severe GI lesions in adult IgAV patients. [ABSTRACT FROM AUTHOR]

Background Staphylococcus lugdunensis ( S. lugdunensis ) is known as a common cause of clinically significant infections in adults although the clinical importance of S. lugdunensis isolates from pediatric samples is less known. The aim of this study is to assess the incidence, characteristics, and outcomes of S. lugdunensis bacteremia (SLB) in children. Methods From January 2009 to March 2014, all blood culture isolates were retrospectively screened for S. lugdunensis . We analyzed the isolates for antimicrobial susceptibility and patients who had developed SLB by reviewing the electronic medical records. Additionally, we identified mecA and blaZ for available isolates by polymerase chain reaction (PCR). Results Of the 647 positive blood cultures during the period, 277 (42.8%) yielded coagulase negative Staphylococcus (CoNS), and 10 of 277 CoNS were S. lugdunensis (3.6% of all CoNS isolates). Of eight SLB episodes identified, seven (87.5%) were considered to have clinically significant bacteremia. All patients had underlying diseases, and all SLB were either healthcare-associated or hospital acquired. There was no infectious endocarditis (IE) development. All patients were treated with antibiotics and recovered without sequelae. We found that the isolates in our study showed higher antibiotic resistance to penicillin (8/8: 100%) and oxacillin (6/8: 75.0%) than previously reported. Among isolates available, we detected mecA in all four isolates resistant to oxacillin and blaZ in 5 of 6 isolates resistant to penicillin. Conclusions S. lugdunensis is a rare but an important cause of bacteremia in children. [ABSTRACT FROM AUTHOR]

This study was the first to describe the hitherto deficiently evaluated alkaline tolerance of Kocuria marina isolate from a pediatric patient with continuous intravenous epoprostenol dosing therapy. Our isolate from blood of a 7-year-old Japanese boy was finally identified as K. marina by the morphological, cultural, and biochemical properties together with the comparative sequence analyses of the 16S rRNA genes. The K. marina isolate, the causative agent of catheter-related blood-stream infection, was not only revealed to be salt tolerant (NaCl 15%), but also demonstrated to be stably survived with no apparent decrease of cell counts for long periods (120 h) in an alkaline environment (pH 8, 9, 10, and 11) at 35 °C. Its remarkable tolerance to the stresses of high alkalinity compared with a clinical Staphylococcus aureus strain should provide consistent interpretation that the environment of high alkalinity (pH 10.2–10.8) measures should be insufficient to inactivate almost all the causative agents including K. marina strains in the solution of epoprostenol (pH 10.4) (Flolan ® , GlaxoSmithKline, Ltd., Tokyo, Japan.). To the best of our knowledge, the first description of the property of being tolerant to high alkalinity that the K. marina isolate exhibited was noteworthy and a useful piece of information. In conclusion, we believe that the present study should be a notification regarding the potential risk of catheter-related blood-stream infections due to K. marina , suggestive of an alkalophile, especially in patients receiving continuous intravenous epoprostenol dosing therapy. [ABSTRACT FROM AUTHOR]

The male endophallic morphology and mitochondrial cytochrome oxidase subunit I ( COI) gene of two parapatric species of the acuticollis species group, Platycerus acuticollis and P. albisomni, were examined at the border between the two species. No morphologically inferred hybrid was found. The endophallic and mitochondrial types of each individual were significantly linked, and the two species inferred by both types were essentially parapatric even at a very local level. We inferred that the reproductive isolation between them is high, although introgressive hybridization occurred rarely. The taxonomical assignment of P. acuticollis and P. albisomni as two distinct species is considered appropriate. [ABSTRACT FROM AUTHOR]

The number of patients with neurodegenerative diseases (NDs) is increasing, along with the growing number of older adults. This escalation threatens to create a medical and social crisis. NDs include a large spectrum of heterogeneous and multifactorial pathologies, such as amyotrophic lateral sclerosis, frontotemporal dementia, Alzheimer's disease, Parkinson's disease, Huntington's disease and multiple system atrophy, and the formation of inclusion bodies resulting from protein misfolding and aggregation is a hallmark of these disorders. The proteinaceous components of the pathological inclusions include several RNA-binding proteins (RBPs), which play important roles in splicing, stability, transcription and translation. In addition, RBPs were shown to play a critical role in regulating miRNA biogenesis and metabolism. The dysfunction of both RBPs and miRNAs is often observed in several NDs. Thus, the data about the interplay among RBPs and miRNAs and their cooperation in brain functions would be important to know for better understanding NDs and the development of effective therapeutics. In this review, we focused on the connection between miRNAs, RBPs and neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Background: Blood transfusion is an important supportive care for high‐risk neuroblastoma. When the number of transfusions increases, transfusion‐associated adverse reactions may be more problematic. However, the factors determining the degree of myelosuppression and the number of transfusions during chemotherapy for high‐risk neuroblastoma remain unclear. Materials and Methods: We investigated patient factors determining the number of required transfusions in 15 high‐risk neuroblastoma patients who received five courses of chemotherapy. Clinical data, cytokine profile and colony‐forming assay with bone marrow samples at diagnosis were analysed. Results: The required number of transfusions of both platelets and erythrocytes decreased once in the second course and then increased as the course progressed. The variability among cases increased as the chemotherapy course progressed. In cases of low peripheral blood platelet count and lower fibrinogen level at diagnosis, the number of platelet transfusions was higher during chemotherapy. In contrast, there was a negative correlation between the forming ability of granulocyte–macrophage or erythroid colonies and the number of erythrocyte transfusions in the latter period. Conclusion: In the early stages of chemotherapy, bone marrow infiltration in neuroblastoma and/or coagulopathy complication may cause thrombocytopenia and requirement of platelet transfusion; conversely, in the later stages, the number of erythrocyte transfusions may be defined by the patient's inherent hematopoietic ability. These factors may be useful in predicting the required number of transfusions. [ABSTRACT FROM AUTHOR]

Background: In contrast to the adult population, limited information is currently available on risk factors for ventilator‐associated pneumonia (VAP) in children. Therapeutic hypothermia has been identified as a risk factor for the early onset of VAP in adults; however, the relationship between VAP and normothermia remains unclear. The present study investigated risk factors for VAP in children, with a focus on the deleterious effects of therapeutic normothermia on VAP. Methods: We retrospectively investigated the clinical characteristics of children treated with mechanical ventilation for more than 48 h and analyzed risk factors for VAP. The endpoint was the onset of VAP by the seventh day after the initiation of mechanical ventilation. Results: Among the 288 patients enrolled, seven (2.4%) developed VAP. No significant differences were observed in clinical backgrounds between the VAP and non‐VAP groups. A univariate analysis identified target temperature management (TTM) at 36°C (p < 0.0001) and methylprednisolone (mPSL) pulse therapy (p = 0.02) as risk factors for VAP. An analysis of the time to the onset of VAP by the Kaplan–Meier plot and log‐rank test revealed a significantly higher incidence of VAP in the TTM group (p < 0.0001) and mPSL pulse group (p = 0.001). Conclusion: TTM at 36°C and mPSL pulse therapy may be risk factors for VAP in the pediatric population. [ABSTRACT FROM AUTHOR]

Eribulin mesylate (ERB) is a synthetic analog of halichondrin B, inhibiting tumor cell growth by disrupting microtubule function. Recently, anticancer drugs have been shown to not only act directly on tumor cells but also to exert antitumor effects by modifying the tumor environment. Although ERB has also been speculated to modify the tumor microenvironment including the immune response to tumors, the precise mechanism remains unclear. In our study, ERB suppressed the tumor growth of MC38 colon cancer in wildtype mice, whereas ERB failed to inhibit the tumor growth in Rag1-deficient mice which lack both B and T cells. Moreover, depletion of either CD4+ or CD8+ T cells abrogated the antitumor effect of ERB, indicating that both CD4+ and CD8+ T cells play an important role in ERB-induced antitumor effects. Furthermore, ERB treatment increased the number of tumor infiltrating lymphocytes (TILs) as well as the expression of activation markers (CD38 and CD69), immune checkpoint molecules (LAG3, TIGIT and Tim3) and cytotoxic molecules (granzyme B and perforin) in TILs. ERB upregulated E-cadherin expression in MC38. CD103 is a ligand of E-cadherin and induces T-cell activation. ERB increased the proportion of CD103+ cells in both CD4+ and CD8+ TILs. The ERB-induced antitumor effect with the increased TIL number and the increased expression of activation markers, inhibitory checkpoint molecules and cytotoxic molecules in TILs was abrogated in CD103-deficient mice. Collectively, these results suggest that ERB exerts antitumor effects by upregulation of E-cadherin expression in tumor cells and subsequent activation of CD103+ TILs. [ABSTRACT FROM AUTHOR]

Objectives Myositis-specific autoantibodies (MSAs) define distinct clinical subsets of idiopathic inflammatory myopathies (IIMs). The anti-nuclear matrix protein 2 (NXP2) antibody, a MSA detected in juvenile/adult IIMs, has been reported to be associated with a high risk of subcutaneous calcinosis, subcutaneous oedema and internal malignancies. The study aimed to clarify the clinical features of anti-NXP2 antibody-positive IIMs in detail. Methods This was a multicentre retrospective observational study on 76 anti-NXP2 antibody-positive patients. The antibody was detected via a serological assay using immunoprecipitation and western blotting. The patients were selected from 162 consecutive Japanese patients with IIMs. Results The cohort of anti-NXP2 antibody-positive IIMs included 29 juvenile patients and 47 adult patients. Twenty-seven (35.5%) patients presented with polymyositis phenotype without dermatomyositis-specific skin manifestations (heliotrope rash or Gottron sign/papules); this was more common in the adults than children (48.9% vs 15.8%, P  < 0.01). Nine (11.8%) patients had subcutaneous calcinosis, and 20 (26.3%) patients had subcutaneous oedema. In addition, the proportion of patients with muscle weakness extending to the distal limbs was high (36 patients [47.4%]) in this cohort. Adult patients had a higher prevalence of malignancy than the general population (age-standardized incidence ratio of malignancies: 22.4). Conclusion Anti-NXP2 antibody-positive IIMs, which include dermatomyositis sine dermatitis, are characterized by atypical skin manifestations and extensive muscular involvement. [ABSTRACT FROM AUTHOR]

Use of immune checkpoint inhibitors that target programmed cell death-1 (PD-1) can lead to various autoimmune-related adverse events (irAEs) including psoriasis-like dermatitis. Our observations on human samples indicated enhanced epidermal infiltration of CD8 T cells, and the pathogenesis of which appears to be dependent on IL-6 in the PD-1 signal blockade-induced psoriasis-like dermatitis. By using a murine model of imiquimod-induced psoriasis-like dermatitis, we further demonstrated that PD-1 deficiency accelerates skin inflammation with activated cytotoxic CD8 T cells into the epidermis, which engage in pathogenic cross-talk with keratinocytes resulting in production of IL-6. Moreover, genetically modified mice lacking PD-1 expression only on CD8 T cells developed accelerated dermatitis, moreover, blockade of IL-6 signaling by anti-IL-6 receptor antibody could ameliorate the dermatitis. Collectively, PD-1 signal blockade-induced psoriasis-like dermatitis is mediated by PD-1 signaling on CD8 T cells, and furthermore, IL-6 is likely to be a therapeutic target for the dermatitis. Tanaka et al investigate the mechanism by which psoriasis-like dermatitis may occur following PD-1 antibody treatment for melanoma. They find that PD-1 loss in CD8 T-cells accelerates dermatitis in a manner depending on IL-6 signaling, suggesting IL-6 as a potential therapeutic target. [ABSTRACT FROM AUTHOR]

In the article, the authors present a case of a 57-year-old Japanese female who was rushed to a hospital due to 2-year history of muscle weakness, scleroderma on the face, upper extremities, chest and abdomen, and widespread papules/scaly erythema to discuss anti-PL7 antibody-positive anti-synthetase syndrome (ASS) with dermatomyositis-linked erythema induced sclerodermatous changes. Also cited are the clinical features of ASS like myositis, arthritis, and fever.

The article presents case study of a 2-year-old boy who was diagnosed with asymptomatic subcutaneous cervical mass due to Actinomyces odontolyticus infection in a pyriform sinus fistula. It mentions that actinomyces is a Gram-positive facultative anaerobe and an endogenous flora of the oral cavity. It states that rRNA-specific polymerase chain reaction using specimen or colony extraction may be important for making a correct diagnosis in a shorter period.

The article presents a case study of a 1 year 11 month-old boy with frequent diarrhea. Topics include diarrhea being watery without blood or mucus and also vomiting once; causing severe infections such as pyelonephritis or bacteremia being one of the leading causes of nosocomial infections; and meropenem being switched to cefotaxime according to the result of antimicrobial susceptibility test.

Pericardial effusion is a potentially fatal complication following hematopoietic stem cell transplantation (HSCT). Therefore, the identification of risk factors could improve the outcome. Prolonged QT dispersion (QTD) and corrected QTD (QTcD) are associated with serious arrhythmias and sudden death in many forms of heart disease. However, no study has evaluated the efficacy of QTD and QTcD to predict pericardial effusion post-HSCT. We studied 89 pediatric HSCT patients to identify preoperative risk factors for pericardial effusion with particular focus on QTD and QTcD. Pericardial effusion occurred in 15 patients (cumulative onset rate: 17.4%) within one year post-HSCT, of which 8 (9.2%) were symptomatic. Patients with pericardial effusion following allogeneic HSCT showed significantly lower overall survival; however, pericardial effusion was not the direct cause of death in any patient. Univariate and multivariate analyses revealed that transplantation-associated thrombotic microangiopathy (TA-TMA) was an independent risk factor for post-HSCT pericardial effusion. In addition, pretransplant QTcD was significantly prolonged in the pericardial effusion group. These results suggest that pediatric patients with abnormally prolonged QTcD before the preparative regimen for HSCT should be regularly followed-up by echocardiography to detect pericardial effusion, particularly when accompanied by complications including TA-TMA. [ABSTRACT FROM AUTHOR]

Background: Providing aftercare to psychiatric inpatients is important for preventing frequent readmissions; however,the lack of social resources is a problem in Japan. The prefectural Tama-Fuchu Public Health Centre has attempted toestablish a new continuous follow-up system for all discharged psychiatric patients in order to reduce the frequency ofreadmissions.Aims: This study aims to evaluate the efficacy of this system.Methods: The subjects of the present study were 200 psychiatric inpatients from the Tokyo catchment area. Thecontinuous follow-up system was applied to 130 subjects for one year in addition to conventional standard care (theintervention group). Seventy subjects received conventional care alone (the comparison group). The incident rate ratios(IRR) of total and involuntary readmission to hospital were compared by survival analysis.Results: During the observation period, there were 41 readmissions and 29 involuntary readmissions in 49,731 persondays.The patients subjected to continuous follow-up showed a trend towards a lower overall risk of readmission (IRR =0.56, 95% CI: 0.29–1.10, p = .057) and a significantly reduced risk of involuntary admission (IRR = 0.48, 95% CI: 0.22–0.96,p = .047).Conclusion: This study provides empirical evidence that providing continuous follow-up examinations as aftercare fordischarged psychiatric patients significantly reduces the incidence of involuntary readmission. [ABSTRACT FROM AUTHOR]

Molecular phylogenies of the genus Platycerus in Japan were characterized based on the nuclear 28S ribosomal RNA and mitochondrial cytochrome oxidase subunit I ( COI) genes. These analyses, combined with our previous morphological information, revealed a detailed diversification process of Platycerus in Japan, as well as estimates of their divergence times. Japanese species were monophyletic and were inferred to have diverged to the acuticollis species group and all other species ca 1.69 Mya. The acuticollis species group then appeared to split into P. viridicuprus and a group including P. takakuwai, P. albisomni and P. acuticollis ca 1.26 Mya. Other specific divergences have occurred primarily since ca 0.33 Mya. Comparing the molecular trees and the morphological tree, we also found introgression of the COI gene in some species. Genetic divergence of Platycerus has occurred intensely in southwestern Japan. [ABSTRACT FROM AUTHOR]

Simple Summary: Imiquimod (IMQ), a synthetic ligand of Toll-like receptor 7, is known to exert antitumor effects. However, the exact mechanisms of the IMQ-induced antitumor effect have not been fully understood. Although both topical IMQ treatment and anti-PD-1 antibody may be used for primary skin lesions or skin metastases of various cancers, the efficacy of each monotherapy for these lesions is insufficient. In our study using a murine tumor model, we show that IFN-γ produced by CD8+ T cells may play a crucial role in the IMQ-induced antitumor effect. In addition, IMQ upregulated PD-1 expression in T cells as well as PD-L1/PD-L2 expression in myeloid cells. Furthermore, we also found that combination therapy of topical IMQ with anti-PD-1 antibody exerted a significantly potent antitumor effect when compared with each single therapy. Therefore, the combination therapy of topical IMQ plus anti-PD-1 antibody is promising therapy for skin cancer. The exact mechanisms of the imiquimod (IMQ)-induced antitumor effect have not been fully understood. Although both topical IMQ treatment and anti-PD-1 antibody may be used for primary skin lesions or skin metastases of various cancers, the efficacy of each monotherapy for these lesions is insufficient. Using a murine tumor model and human samples, we aimed to elucidate the detailed mechanisms of the IMQ-induced antitumor effect and analyzed the antitumor effect of combination therapy of topical IMQ plus anti-PD-1 antibody. Topical IMQ significantly suppressed the tumor growth of MC38 in wildtype mice. IMQ upregulated interferon γ (IFN-γ) expression in CD8+ T cells in both the lymph nodes and the tumor, and the antitumor effect was abolished in both Rag1-deficient mice and IFN-γ-deficient mice, indicating that IFN-γ produced by CD8+ T cells play a crucial role in the IMQ-induced antitumor effect. IMQ also upregulated PD-1 expression in T cells as well as PD-L1/PD-L2 expression in myeloid cells, suggesting that IMQ induces not only T-cell activation but also T-cell exhaustion by enhanced PD-1 inhibitory signaling. Combination therapy of topical IMQ plus anti-PD-1 antibody exerted a significantly potent antitumor effect when compared with each single therapy, indicating that the combination therapy is a promising therapy for the skin lesions of various cancers. [ABSTRACT FROM AUTHOR]

We report a rare case of a complete hydatidiform mole with two or more coexisting fetuses where both infants survived without complications. A male infant weighing 1258 g and a female infant weighing 880 g were delivered without complications and discharged 95 days after the birth. The analysis of DNA microsatellite polymorphisms indicated that the mole was of paternal origin and probably homozygous. The mother suffered from multiple pulmonary metastasis of the hydatidiform mole which was detected 3 days after the surgery and was successfully treated with methotrexate. A complete hydatidiform mole with two or more coexisting fetuses produces a dilemma between immediate termination and pregnancy continuation. Although the present case resulted in a favorable outcome, a review of the 14 reported cases suggests that the high fetal loss rate (90%) must be a consideration in the decision regarding management of such a pregnancy. [ABSTRACT FROM AUTHOR]