RESUMO
A 44-year-old woman was diagnosed with acute myeloid leukemia (RUNX1::RUNX1T1 translocation) and received induction chemotherapy with idarubicin hydrochloride and cytosine arabinoside. The pneumonia that had been present since admission worsened, and a drug-induced skin rash appeared. On day 17, she presented with respiratory failure and shock, complicated by hemoconcentration and hypoalbuminemia. This was considered capillary leak syndrome due to pneumonia and drug allergy, so she was started on pulse steroid therapy and IVIG, and was intubated on the same day. On day 18, venovenous-extracorporeal membrane oxygenation (VV-ECMO) was started due to worsening blood gas parameters despite ventilatory management. Bronchoalveolar lavage fluid was serous, and both blood and sputum cultures yielded negative. The patient was weaned from VV-ECMO on day 26 as the pneumonia improved with recovery of hematopoiesis. She was disoriented, and a CT scan on day 28 revealed cerebral hemorrhage. Her strength recovered with rehabilitation. After induction chemotherapy, RUNX1::RUNX1T1 mRNA was not detected in bone marrow. The patient received consolidation chemotherapy, and has maintained complete remission. Severe respiratory failure during induction chemotherapy for acute leukemia can be fatal, but VV-ECMO may be lifesaving.
Assuntos
Síndrome de Vazamento Capilar , Oxigenação por Membrana Extracorpórea , Leucemia Mieloide Aguda , Pneumonia , Insuficiência Respiratória , Humanos , Feminino , Adulto , Subunidade alfa 2 de Fator de Ligação ao Core , Quimioterapia de Indução , Síndrome de Vazamento Capilar/complicações , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/terapiaRESUMO
Background and Objectives: The Wakayama prefecture is endemic for two types of tick-borne rickettsioses: Japanese spotted fever (JFS) and scrub typhus (ST). Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne hemorrhagic viral disease with a high mortality rate and is often difficult to differentiate from such rickettsioses. SFTS cases have recently increased in Wakayama prefecture. For early diagnosis, this study aimed to evaluate the clinical characterization of such tick-borne infections in the co-endemic area. Materials and Methods: The study included 64 febrile patients diagnosed with tick-borne infection in Wakayama prefecture between January 2013 and May 2022. Medical records of 19 patients with SFTS and 45 with rickettsiosis (JSF, n = 26; ST, n = 19) were retrospectively examined. The receiver operating curve (ROC) and area under the curve (AUC) were calculated to evaluate potential factors for differentiating SFTS from rickettsiosis. Results: Adults aged ≥70 years were most vulnerable to tick-borne infections (median, 75.5 years; interquartile range, 68.5-84 years). SFTS and rickettsiosis occurred mostly between summer and autumn. However, no significant between-group differences were found in age, sex, and comorbidities; 17 (89%) patients with SFTS, but none of those with rickettsiosis, experienced gastrointestinal symptoms such as vomiting, abdominal pain, and diarrhea. Meanwhile, 43 (96%) patients with rickettsiosis, but none of those with SFTS, developed a skin rash. The AUCs of white blood cells (0.97) and C-reactive protein (CRP) levels (0.98) were very high. Furthermore, the differential diagnosis of SFTS was significantly associated with the presence of gastrointestinal symptoms (AUC 0.95), the absence of a skin rash (AUC 0.98), leukopenia <3.7 × 109/L (AUC 0.95), and low CRP levels < 1.66 mg/dL (AUC 0.98) (p < 0.001 for each factor). Conclusions: Clinical characteristics and standard laboratory parameters can verify the early diagnosis of SFTS in areas where tick-borne infections are endemic.
Assuntos
Exantema , Phlebovirus , Infecções por Rickettsia , Tifo por Ácaros , Febre Grave com Síndrome de Trombocitopenia , Doenças Transmitidas por Carrapatos , Adulto , Humanos , Febre Grave com Síndrome de Trombocitopenia/diagnóstico , Febre Grave com Síndrome de Trombocitopenia/epidemiologia , Estudos Retrospectivos , Japão/epidemiologia , Infecções por Rickettsia/diagnóstico , Infecções por Rickettsia/epidemiologia , Tifo por Ácaros/complicações , Tifo por Ácaros/diagnóstico , Tifo por Ácaros/epidemiologia , Doenças Transmitidas por Carrapatos/diagnósticoRESUMO
Guillain-Barré syndrome (GBS) is a rare neurological complication of allogeneic hematopoietic stem cell transplantation (HSCT). The pathogenesis of post-HSCT GBS is unclear. Here, we report a case of GBS coincident with Epstein-Barr virus (EBV) and cytomegalovirus (CMV) reactivation that occurred after HSCT in a patient with myelodysplastic syndrome. A 61-year-old man was admitted to our hospital because of gait disturbance due to lower limb muscle weakness, which arose during treatment for chronic graft-versus-host disease (GVHD) five months after allogeneic HSCT. He was diagnosed with GBS based on his clinical course, cerebrospinal fluid analysis, and a nerve conduction study. At that time, he exhibited EBV and CMV reactivation. GBS improved after intravenous injection of immunoglobulins. Our case suggests that reactivation of EBV and CMV during treatment for chronic GVHD may induce GBS, and that rapidly progressive muscular weakness coincident with EBV or CMV reactivation can be a diagnostic sign of GBS after allogeneic HSCT.
Assuntos
Síndrome de Bronquiolite Obliterante , Infecções por Citomegalovirus , Infecções por Vírus Epstein-Barr , Doença Enxerto-Hospedeiro , Síndrome de Guillain-Barré , Transplante de Células-Tronco Hematopoéticas , Masculino , Humanos , Pessoa de Meia-Idade , Herpesvirus Humano 4/fisiologia , Transplante de Medula Óssea/efeitos adversos , Citomegalovirus , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Síndrome de Guillain-Barré/terapia , Síndrome de Guillain-Barré/complicações , Transplante Homólogo/efeitos adversos , Doença Enxerto-Hospedeiro/complicações , Ativação Viral/fisiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversosRESUMO
Kabuki syndrome (KS) is a rare congenital disorder commonly complicated by humoral immunodeficiency. Patients with KS present with mutation in the histone-lysine N-methyltransferase 2D (KMT2D) gene. Although various KMT2D mutations are often identified in lymphoma and leukemia, those encountered in aplastic anemia (AA) are limited. Herein, we present the case of a 45-year-old Japanese man who developed severe pancytopenia and hypogammaglobulinemia. He did not present with any evident malformations, intellectual disability, or detectable levels of autoantibodies. However, B-cell development was impaired. Therefore, a diagnosis of very severe AA due to a hypoplastic marrow, which did not respond to granulocyte colony-stimulating factor, was made. The patient received umbilical cord blood transplantation but died from a Pseudomonas infection before neutrophil engraftment. Trio whole-exome sequencing revealed a novel missense heterozygous mutation c.15959G >A (p.R5320H) in exon 50 of the KMT2D gene. Moreover, Sanger sequencing of peripheral blood and bone marrow mononuclear cells and a skin biopsy specimen obtained from this patient identified this heterozygous mutation, suggesting that de novo mutation associated with KS occurred in the early embryonic development. Our case showed a novel association between KS mutation and adult-onset AA.
Assuntos
Anormalidades Múltiplas/genética , Anemia Aplástica/genética , Proteínas de Ligação a DNA/genética , Face/anormalidades , Doenças Hematológicas/genética , Mutação , Proteínas de Neoplasias/genética , Doenças Vestibulares/genética , Anormalidades Múltiplas/enzimologia , Anormalidades Múltiplas/terapia , Aloenxertos , Anemia Aplástica/enzimologia , Anemia Aplástica/terapia , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Evolução Fatal , Doenças Hematológicas/enzimologia , Doenças Hematológicas/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Infecções por Pseudomonas , Doenças Vestibulares/enzimologia , Doenças Vestibulares/terapiaRESUMO
Endoplasmic reticulum stress activates inositol-requiring enzyme 1α (IRE1α) and protein kinase, R-like endoplasmic reticulum kinase (PERK), the two principal regulators of the unfolded protein response (UPR). In multiple myeloma, adaptive IRE1α signaling is predominantly activated and regulates cell fate along with PERK. Recently, we demonstrated that GNF-2, an allosteric c-Abl inhibitor, rheostatically enhanced IRE1α activity and induced apoptosis through c-Abl conformational changes in pancreatic ß cells. Herein, we analyzed whether the pharmacological modulation of c-Abl conformation resulted in anti-myeloma effects. First, we investigated the effects of GNF-2 on IRE1α activity and cell fate, followed by an investigation of the anti-myeloma effects of asciminib, a new allosteric c-Abl inhibitor. Finally, we performed RNA sequencing to characterize the signaling profiles of asciminib. We observed that both GNF-2 and asciminib decreased cell viability and induced XBP1 mRNA splicing in primary human myeloma cells and myeloma cell lines. RNA sequencing identified the induction of UPR- and apoptosis-related genes by asciminib. Asciminib re-localized c-Abl to the endoplasmic reticulum, and its combination with a specific IRE1α inhibitor, KIRA8, enhanced cell death with the reciprocal induction of CHOP mRNA expression. Together, the allosteric inhibition of c-Abl-activated UPR with anti-myeloma effects; this could be a novel therapeutic target for multiple myeloma.
Assuntos
Mieloma Múltiplo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/genética , Endorribonucleases/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Resposta a Proteínas não Dobradas , Estresse do Retículo Endoplasmático , Morte Celular , RNA Mensageiro/genética , Proteína 1 de Ligação a X-Box/metabolismoRESUMO
Background: Neurofibromatosis type 1 (NF1) is a hereditary cancer syndrome characterized by multiple café-au-lait macules on the skin. Lymphoproliferative malignancies associated with NF1 are limited, although the most common are brain tumors. Case presentation: A 22-year-old woman with NF1 was admitted due to abdominal pain and bloody diarrhea. Her laboratory data exhibited macrocytic anemia and elevated IgA levels. Image studies showed diffuse increased wall thickening in the transverse and descending colon without lymphadenopathy and hepatosplenomegaly. A colonoscopy revealed a hemorrhagic ulcerated mass. Pathological analysis of the tumor tissues confirmed IgA-expressing mucosa-associated lymphoid tissue (MALT) lymphoma with histological transformation. Moreover, whole-exome sequencing in tumor tissues and peripheral blood mononuclear cells identified a somatic frameshift mutation of the A20 gene, which represents the loss of function. The patient responded well to R-CHOP chemotherapy, but the disease relapsed after 1 year, resulting in a lethal outcome. Conclusions: MALT lymphoma in children and young adults is extremely rare and is possibly caused by acquired genetic changes. This case suggests a novel association between hereditary cancer syndrome and early-onset MALT lymphoma.
Assuntos
Linfoma de Zona Marginal Tipo Células B , Linfoma Difuso de Grandes Células B , Neurofibromatose 1 , Humanos , Criança , Feminino , Adulto Jovem , Adulto , Neurofibromatose 1/complicações , Neurofibromatose 1/genética , Neurofibromatose 1/patologia , Linfoma de Zona Marginal Tipo Células B/complicações , Leucócitos Mononucleares , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Imunoglobulina ARESUMO
Background and Objectives: The incidence of coronavirus disease 2019 (COVID-19) has increased in Wakayama, Japan, due to the spread of the highly infectious B.1.1.7 variant. Before this event, the medical systems were almost unaffected. We aimed to assess the clinical characteristics of patients hospitalized with COVID-19 and the risk factors for therapeutic intervention of remdesivir during the fourth pandemic period in Wakayama, Japan. Materials and Methods: This single-center retrospective study enrolled 185 patients with mild to moderate COVID-19 hospitalized in our hospital without intensive care between 14 March and 31 May 2021. Results: In this period, 125 (67.6%) of the 185 patients had the B.1.1.7 variant. Sixty-three patients (34.1%) required remdesivir treatment. Age upon admission and length of hospitalization were significantly different between remdesivir treatment and careful observation groups (mean (standard deviation); 59.6 (14.7) versus 45.3 (20.6) years; p < 0.001 and median (interquartile range); 10 (9-12) versus 9 (8-10) years; p < 0.001). One patient was transferred to another hospital because of disease progression. At hospital admission, age ≥60 years (odds ratio (OR) 6.90, p < 0.001), a previous history of diabetes mellitus (OR 20.9, p = 0.002), B.1.1.7 variant (OR 5.30; p = 0.005), lower respiratory symptoms (OR 3.13, p = 0.011), headache (OR 3.82, p = 0.011), and fever ≥37.5 °C (OR 4.55, p = 0.001) were independent risk factors to require remdesivir treatment during the admission. Conclusions: Many patients with mild to moderate COVID-19 required the therapeutic intervention of remdesivir during the fourth pandemic period in Wakayama, Japan. From the clinical data obtained at admission, these risk factors could contribute to a prediction regarding the requirement of remdesivir treatment in cases of mild to moderate COVID-19.
Assuntos
Tratamento Farmacológico da COVID-19 , SARS-CoV-2 , Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Humanos , Japão/epidemiologia , Pessoa de Meia-Idade , Pandemias , Estudos Retrospectivos , Fatores de RiscoRESUMO
Background: The prevalence of nonalcoholic fatty liver disease (NAFLD) has been increasing worldwide. The existence of a relationship between the microbiota and the pathology of hepatic steatosis is also becoming increasingly clear. AST-120, an oral spherical carbon adsorbent, has been shown to be useful for delaying dialysis initiation and improving uremic symptoms in patients with chronic kidney disease. However, little is known about the effect of AST-120 on fatty liver.Methods: AST-120 (5% w/w) was administrated to 6-week-old male db/db mice for 8 weeks. The body weight, blood glucose and food consumption were examined. Hepatic triglyceride (TG) levels, lipid droplets and epididymal fat cell size were measured. The gut microbiota compositions were investigated in feces and cecum.Results: Significant decreases of the hepatic weight and hepatic TG levels were observed in the AST-120-treated db/db mice. Furthermore, AST-120 treatment was also associated with a decrease of Bacteroidetes, increase of Firmicutes, and a reduced ratio of Bacteroidetes to Firmicutes (B/F ratio) in the feces in the db/db mice. The B/F ratio in the feces was correlated with the liver weight and area of the liver occupied by lipid droplets in the db/db mice.Conclusions: These data suggest that AST-120 treatment alters the composition of the fecal microbiota and suppresses hepatic TG levels in the db/db mice.
Assuntos
Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica , Animais , Carbono/metabolismo , Dieta Hiperlipídica , Humanos , Metabolismo dos Lipídeos , Fígado , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Óxidos , TriglicerídeosRESUMO
TAFRO syndrome, a rare subtype of idiopathic multicentric Castleman disease, manifests as thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly. Thrombotic microangiopathy, including renal dysfunction, is frequently associated with this syndrome. TAFRO syndrome can be life threatening and show rapid progression, and the diagnosis and management of this disorder remain challenging. A 48-year-old woman was diagnosed with TAFRO syndrome complicated by thrombotic microangiopathy based on the clinical and histopathological findings. After receiving high-dose steroids, her thrombocytopenia and anasarca did not improve. The patient subsequently received a combination of cyclosporine A and rituximab as second-line therapy, which resulted in a significant gradual improvement in the clinical symptoms. Meanwhile, her platelet count increased to more than 40 × 109/L; however, she developed intracranial hemorrhage. Following surgical evacuation, the patient recovered with an achievement of sustained remission. Based on these findings, attention should be paid to life-threatening bleeding associated with local thrombotic microangiopathy even when intensive treatment is administered for TAFRO syndrome.
Assuntos
Hiperplasia do Linfonodo Gigante , Ciclosporina/uso terapêutico , Feminino , Humanos , Hemorragias Intracranianas/induzido quimicamente , Hemorragias Intracranianas/tratamento farmacológico , Pessoa de Meia-Idade , Rituximab/uso terapêuticoRESUMO
Erdheim-Chester disease (ECD) is a very rare form of the non-Langerhans histiocytic multisystem disorder. The cardiac involvement is often challenging and is associated with poor prognosis. Transthoracic echocardiography was used to detect right atrium tumors in a 62-year-old man with heart failure who was admitted to our hospital. The circumferential soft tissue sheathing of the aorta (coated aorta) and fat infiltration around the kidneys (hairy kidneys) was seen on a contrast-enhanced computed tomography strongly suspecting ECD imaging. The patient was diagnosed with ECD based on histopathology reports of the surgical resection tumor. The characteristic imaging findings of ECD may contribute to an early and accurate diagnosis.
Assuntos
Doença de Erdheim-Chester , Neoplasias , Ecocardiografia , Doença de Erdheim-Chester/diagnóstico por imagem , Átrios do Coração/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Inositol-requiring enzyme 1α (IRE1α), along with protein kinase R-like endoplasmic reticulum kinase (PERK), is a principal regulator of the unfolded protein response (UPR). Recently, the 'mono'-specific IRE1α inhibitor, kinase-inhibiting RNase attenuator 6 (KIRA6), demonstrated a promising effect against multiple myeloma (MM). Side-stepping the clinical translation, a detailed UPR phenotype in patients with MM and the mechanisms of how KIRA8 works in MM remains unclear. METHODS: We characterized UPR phenotypes in the bone marrow of patients with newly diagnosed MM. Then, in human MM cells we analyzed the possible anti-tumor mechanisms of KIRA8 and a Food and Drug Administration (FDA)-approved drug, nilotinib, which we recently identified as having a strong inhibitory effect against IRE1α activity. Finally, we performed an RNA-sequence analysis to detect key IRE1α-related molecules against MM. RESULTS: We illustrated the dominant induction of adaptive UPR markers under IRE1α over the PERK pathway in patients with MM. In human MM cells, KIRA8 decreased cell viability and induced apoptosis, along with the induction of C/EBP homologous protein (CHOP); its combination with bortezomib exhibited more anti-myeloma effects than KIRA8 alone. Nilotinib exerted a similar effect compared with KIRA8. RNA-sequencing identified Polo-like kinase 2 (PLK2) as a KIRA8-suppressed gene. Specifically, the IRE1α overexpression induced PLK2 expression, which was decreased by KIRA8. KIRA8 and PLK2 inhibition exerted anti-myeloma effects with apoptosis induction and the regulation of cell proliferation. Finally, PLK2 was pathologically confirmed to be highly expressed in patients with MM. CONCLUSION: Dominant activation of adaptive IRE1α was established in patients with MM. Both KIRA8 and nilotinib exhibited anti-myeloma effects, which were enhanced by bortezomib. Adaptive IRE1α signaling and PLK2 could be potential therapeutic targets and biomarkers in MM.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Endorribonucleases/antagonistas & inibidores , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Terapia de Alvo Molecular , Mieloma Múltiplo/tratamento farmacológico , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Adulto , Idoso , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Movimento Celular , Proliferação de Células , Estudos Transversais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Prognóstico , Pirazinas/administração & dosagem , Pirimidinas/administração & dosagem , Estudos Retrospectivos , Células Tumorais CultivadasRESUMO
Currently, the humanized anti-C5 monoclonal antibody, eculizumab, is widely used for treating paroxysmal nocturnal hemoglobinuria (PNH) due to its effects on suppression of intravascular hemolysis and resulting improvement in quality of life. However, in some cases, this treatment is refractory or is associated with meningococcal meningitis. No region-specific analyses have been published, and currently, information on region specificity and genetic factors is limited. We present here the results of a retrospective study involving eight patients with PNH who were treated with eculizumab in our hospital in Wakayama, Japan. The median age of these patients was 77 (range 23-88) years. Six patients had a complication of aplastic anemia, four patients had a history of thrombosis, and two experienced hemolytic episodes. Before initiating eculizumab treatment, the median serum LDH level was 1,192 IU/l (range 755-1,525 IU/l). Serum LDH levels normalized in five patients within a month of initiating therapy and PNH-related symptoms disappeared. C5 gene mutations were identified in the three patients who did not respond to eculizumab.
Assuntos
Hemoglobinúria Paroxística , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados , Humanos , Japão , Pessoa de Meia-Idade , Qualidade de Vida , Estudos Retrospectivos , Adulto JovemRESUMO
There are three kinds of adipocytes; white adipocytes accumulate excess energy as fat, whereas brown/beige adipocytes dissipate energy through expression of uncoupling protein 1 (UCP1). Obesity, a feature of excess accumulation of white adipocytes in a body, is one of the risk factors for onset of various diseases in dogs. As the first step to explore adipose genes related to dog obesity, we examined relationships among mRNA levels of putative molecules related to adipogenesis and function of adipocytes in fat of hospitalized dogs. Gonadal adipose tissues were collected from a total of 29 dogs, and the gene expression levels were examined by quantitative RT-PCR analysis. The multicollinearity analysis revealed that body condition score (BCS), which reflects adiposity, did not correlate with expression levels of any genes but correlated with age of dog. Bone morphogenetic protein (BMP) pathway stimulates not only commitment of mesenchymal stem cells to white adipocyte-lineage cells but also brown/beige adipogenesis. Some relationships between expression levels of BMP receptors were significant; especially, expression levels of activin receptor-like kinase (Alk) 3 (a BMP type I receptor) positively related to those of Alk2 (another BMP type I receptor), activin receptor type II (ActRII) A (a type II receptor to transmit BMP signal), ActRIIB (another type II receptor to transmit BMP signal) and BMP receptor type 2 (Bmpr2). PR domain containing 16 (Prdm16) expression levels strongly correlated with expression levels of ActRIIB. Although PRDM16 is known to stimulate brown/beige adipogenesis, expression levels of Ucp1 did not correlate with those of Prdm16. On the other hand, expression levels of Ucp1 correlated with those of Alk6. The present study suggests close relationships among adipose expressions of BMP signal components, and the relationships of expression levels of BMP receptor and those of Prdm16 or Ucp1 in dogs. Further studies using more dogs with various BCS potentially lead to identification of adipose factors to relate with adiposity in dogs.
Assuntos
Adipócitos/metabolismo , Adipogenia/genética , Expressão Gênica , Animais , Biomarcadores , Células Cultivadas , Cães , Perfilação da Expressão GênicaRESUMO
A 63-year-old woman was admitted to our hospital to receive a fourth course of modified rituximab-ESHAP chemotherapy for relapsed primary breast diffuse large B-cell lymphoma. She developed hemophagocytic lymphohistiocytosis (HLH) 20 days after admission. Polymerase chain reaction (PCR) detected cytomegalovirus (CMV) DNA in her peripheral blood; therefore, she was diagnosed with CMV-associated HLH and consequently treated with foscarnet (FCN). Her general condition and pancytopenia soon improved, and the antiviral drug was stopped for 1 week. However, she suddenly became disoriented 10 days later, and this condition rapidly worsened. Cerebrospinal fluid (CSF) examination revealed an elevated white blood cell count with lymphocytic predominance and a high CMV DNA load, prompting a final diagnosis of CMV meningoencephalitis. We began intravenous combination therapy with FCN and ganciclovir (GCV), and her conscious state gradually improved. CMV DNA sequencing did not reveal drug resistance associated with mutations, and intravenous GCV was stopped for 1 week. FCN treatment was then continued until CMV DNA was no longer detected in her CSF samples via PCR. CMV meningoencephalitis is a rare neurological infection complicated with hematological malignancy in non-transplant patients and can be serious and life-threatening with a high mortality rate. This infection requires a differential diagnosis of consciousness impairment that develops in a patient with lymphoid malignancy during chemotherapy.
Assuntos
Antivirais/uso terapêutico , Infecções por Citomegalovirus/diagnóstico , Linfoma Difuso de Grandes Células B/virologia , Meningoencefalite/virologia , Adulto , Criança , Citomegalovirus , Infecções por Citomegalovirus/tratamento farmacológico , DNA Viral/sangue , Feminino , Foscarnet , Ganciclovir , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Pessoa de Meia-Idade , Terapia de SalvaçãoRESUMO
We managed a patient with acute myeloid leukemia (AML) who showed refractory ascites that developed in late-phase cord blood transplantation (CBT). The ascites obverted 5 months after CBT. The liver was atrophic, and serum hyaluronic acid was elevated at the onset, suggesting fibrotic changes in the liver. The ascites were transiently improved by cell-free and concentrated ascites reinfusion therapy (CART) and corticosteroid administration; however, the patient died from anasarca and recurrent AML 378 d after CBT. The etiology of the ascites is not well understood; therefore, additional studies on similar patients should be explored for proper management.
Assuntos
Ascite/terapia , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Humanos , Cirrose HepáticaRESUMO
Retinal prosthesis or artificial retina is a promising modality of treatment for outer retinal degeneration, caused by primary and secondary loss of photoreceptor cells, in hereditary retinal dystrophy and age-related macular degeneration, respectively. Okayama University-type retinal prosthesis (OUReP) is a photoelectric dye-coupled polyethylene film which generates electric potential in response to light and stimulates nearby neurons. The dye-coupled films were implanted by vitreous surgery in the subretinal space of monkey eyes with macular degeneration which had been induced by cobalt chloride injection from the scleral side. A pilot 1-month observation study involved 6 monkeys and a pivotal 6-month observation study involved 8 monkeys. Of 8 monkeys in 6-month group, 3 monkeys underwent dye-coupled film removal at 5 months and were observed further for 1 month. The amplitude of visual evoked potential which had been reduced by macular degeneration did recover at 1 month after film implantation and maintained the level at 6 months. Optical coherence tomography showed no retinal detachment, and full-field electroretinograms maintained a-wave and b-wave amplitudes, indicative of no retinal toxicity. Pathological examinations after 6-month implantation showed structural integrity of the inner retinal layer in close apposition to dye-coupled films. The implanted films which were removed by vitrectomy 5 months later showed light-evoked surface electric potentials by scanning Kelvin probe measurement. The photoelectric dye-coupled film (OUReP), which serves as a light-receiver and a displacement current generator in the subretinal space of the eye, has a potential for recovering vision in diseases with photoreceptor cell loss, such as retinitis pigmentosa and age-related macular degeneration.
Assuntos
Potenciais Evocados Visuais , Degeneração Macular/cirurgia , Implantação de Prótese/instrumentação , Retina/cirurgia , Próteses Visuais , Compostos de Anilina/química , Compostos de Anilina/efeitos da radiação , Animais , Modelos Animais de Doenças , Estudos de Viabilidade , Luz , Macaca fascicularis , Degeneração Macular/patologia , Degeneração Macular/fisiopatologia , Projetos Piloto , Polietileno/química , Desenho de Prótese , Recuperação de Função Fisiológica , Retina/patologia , Retina/fisiopatologia , Propriedades de Superfície , Tiazóis/química , Tiazóis/efeitos da radiação , Fatores de TempoRESUMO
Common variable immunodeficiency (CVID) is the most frequently diagnosed congenital immunodeficiency and is characterized by dysfunctional antibody production. It often occurs at the age of ≥10 years. Here we reported a case of a 46-year-old man confirmed with adult-onset CVID. He was effectively treated with cord blood transplant (CBT). The patient was observed with repeated upper respiratory infection a few years back and was referred to our department owing to a marked decrease in neutrophil counts and progression of anemia. Laboratory tests confirmed hypogammaglobulinemia, but no autoantibodies were detected. Bone marrow aspiration showed a hypocellular marrow with predominantly mature lymphocytes. T-cell receptor excision circle assay revealed a reduction in T-cell neogenesis. Further, multicolor flow cytometry analysis revealed a low differentiation of B cells; subsequently, CVID was confirmed in the patient. The patient had a severe clinical course and therefore, received CBT for the treatment. After the transplantation, the hematopoiesis was restored and the serum immunoglobulin levels returned to normal. The patient exhibited a favorable clinical course. Nevertheless, there is no precise definition to establish the disease concept of CVID. Also, most of the potential cases are predominantly reported in adults. Therefore, further data on cases with CVID should be accumulated to establish the diagnostic criteria as well as treatment modalities.
Assuntos
Agamaglobulinemia , Imunodeficiência de Variável Comum/terapia , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Linfócitos B/citologia , Humanos , Masculino , Pessoa de Meia-Idade , Linfócitos T/citologiaRESUMO
DNA double-strand breaks (DSBs) caused by ultrasound were evaluated in a quantitative manner by single-molecule fluorescence microscopy. We compared the effect of time-interval (or pulse) sonication to that of continuous wave (CW) sonication at a fixed frequency of 30â kHz. Pulses caused fewer DSBs than CW sonication under the same total input ultrasound energy when the pulse repetition period was above the order of a second. In contrast, pulses caused more DSBs than CW sonication for pulse widths shorter than a second. These effect of ultrasound on DNA were interpreted in terms of the time-dependent decay in the probability of breakage during the duration of a pulse. We propose a simple phenomenological model by considering a characteristic decay in the probability of DSBs during single-pulse sonication, which reproduces the essence of the experimental trend. In addition, a data analysis revealed a characteristic scaling behavior between the number of pulses and the number of DSBs.
Assuntos
DNA/química , Ondas Ultrassônicas , DNA/genética , Quebras de DNA de Cadeia Dupla , Microscopia de FluorescênciaRESUMO
BACKGROUND: Our search for plant-derived ceramides from sustainable sources led to the discovery of ceramides and glucosylceramides in wine lees. OBJECTIVE: This study evaluated the efficacy and safety of wine lees extract (WLE)-derived ceramides and glucosylceramides in enhancing skin barrier function. METHODS: A randomized, double-blind, placebo-controlled study was conducted with 30 healthy Japanese subjects aged 20-64. Subjects were allocated to receive either the WLE-derived ceramides and glucosylceramides (test group) or placebo for 12 weeks. The primary outcome was transepidermal water loss (TEWL), and secondary outcomes included skin hydration, visual analog scale (VAS) of itching sensation, and the Japanese Skindex-29. RESULTS: One participant withdrew for personal reasons, resulting in 29 subjects for data analysis (placebo n = 15; test n = 14). The test group showed a tendency of lower TEWL compared to the placebo after 8 weeks (p = 0.07). Furthermore, after 12 weeks of administration, the test group had significantly lower TEWL than the placebo (p = 0.04). On the other hand, no significant differences were observed in the secondary outcome parameters. No adverse events related to the supplements were reported. CONCLUSIONS: Oral supplementation of WLE-derived ceramides and glucosylceramides is a prominent and safe approach to enhancing skin barrier function and health. TRIAL REGISTRATION: (UMIN000050422).