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Recently, augmenting the pulsation of the internal cerebral vein (ICV) has been reported to be a predictor of premature intraventricular hemorrhage (IVH); however, prophylaxis for IVH has not yet been established. Venous pulsation is a marker of central venous pressure elevation and may be improved after heart failure treatment. Herein, we report two cases of low-birth-weight infants (29 weeks and 31 weeks of gestational age), who exhibited improvements in ICV pulsation with relief of hemodynamically significant patent ductus arteriosus (hs-PDA) following indomethacin administration. ICV flow patterns were continuously flat early after birth. Thereafter, both patients demonstrated ICV pulsation augmentation with PDA progression and brain natriuretic peptide (BNP) elevation at 52 h and 39 h after birth (in infants born at 29 and 31 weeks of gestational age, respectively). After relieving PDA with indomethacin administration, both infants exhibited an improvement in ICV pulsation with decreased BNP levels. In both cases, ICV pulsation increased when PDA became hemodynamically significant with BNP elevation, and the pulsation improved by reduction in ductal flow with decreasing BNP when PDA was relieved by indomethacin administration. The association between hs-PDA and elevated ICV pulsation indicates that hs-PDA likely leads to heightened central venous pressure. Additionally, indomethacin treatment was effective in reducing the exacerbated ICV pulsation caused by heart failure due to hs-PDA. These cases suggest that treatment for heart failure might improve the augmented ICV pulsation, which is related to the development of premature IVH. However, further studies are needed to confirm this association.
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A 15-year-old male has been experiencing fever, limb pain during exercise, and reduced sweating since childhood. During an investigation into his fever, a family history of Fabry disease was discovered, prompting a referral to our department. He was diagnosed with Fabry disease based on decreased alpha-galactosidase A (α-Gal A) activity. Concurrently, his mother was found to have experienced limb pain during fevers since childhood, and she was also diagnosed with Fabry disease based on decreased α-Gal A activity. In the genetic analysis of both individuals, the IVS1+17A>G GLA variant was identified. This variant is considered benign and not classified as a pathogenic variant. Enzyme replacement therapy has been effective in improving clinical symptoms. His sister, who has not been diagnosed with Fabry disease due to normal clinical symptoms and α-GAL A activity, also had the same variant. Among the various GLA variants, many are classified as benign rather than pathogenic. In the present cases, the possibility of other factors that cannot be identified by genetic analysis is suggested, making this case significant and worth reporting.
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In this immunohistological study on the peripheral retina of 3-year-old beagle dogs, excised retina specimens were immunostained with antibodies against nestin, Oct4, Nanog, Sox2, CDX2, cytokeratin 18 (CK 18), RPE65, and YAP1, as well as hematoxylin and DAPI, two nuclear stains. Our findings revealed solitary cysts of various sizes in the inner retina. Intriguingly, a mass of small round cells with scant cytoplasms was observed in the cavity of small cysts, while many disorganized cells partially occupied the cavity of the large cysts. The small cysts were strongly positive for nestin, Oct4, Nanog, Sox2, CDX2, CK18, and YAP1. RPE65-positive cells were exclusively observed in the tissue surrounding the cysts. Since RPE65 is a specific marker of retinal pigment epithelial (RPE) cells, the surrounding cells of the peripheral cysts were presumably derived from RPE cells that migrated intraretinally. In the small cysts, intense positive staining for nestin, a marker of retinal stem cells, seemed to indicate that they were derived from retinal stem cells. The morphology and positive staining for markers of blastocyst and RPE cells indicated that the small cysts may have formed structures resembling the blastocyst, possibly caused by the interaction between retinal stem cells and migrated RPE cells.
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Retina , Epitelio Pigmentado de la Retina , Animales , Perros , Retina/metabolismo , Epitelio Pigmentado de la Retina/metabolismo , Epitelio Pigmentado de la Retina/citología , Nestina/metabolismo , Blastocisto/metabolismo , Blastocisto/citología , Biomarcadores/metabolismo , Factores de Transcripción SOXB1/metabolismo , Células Madre/metabolismo , Células Madre/citología , Inmunohistoquímica , Enfermedades de los Perros/metabolismo , Enfermedades de los Perros/patologíaRESUMEN
Cardiomyopathy is a rare but serious complication associated with neuroblastoma. The brain natriuretic peptide level led to a diagnosis of secondary dilated cardiomyopathy before the worsening of heart failure symptoms.
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BACKGROUND: Individuals with severe motor and intellectual disabilities have become an aging population, and high cancer morbidity and mortality are critical issues affecting their survival. Cancer screening is a crucial method of resolving this issue; however, a suitable screening method for them has not been established. METHODS: We used ultrasonography alone and performed breast cancer screening for women over 30 years old in our facility from 2016 to 2023. We observed the outcomes and calculated the recall/detection rate in this screening. RESULTS: Three cases among 379 tested positive in this screening, all of which underwent radical surgery. They are alive and well without relapse present. We detected these breast cancer cases with a low recall rate. CONCLUSION: We were able to successfully detect breast cancer cases using ultrasonography alone. Ultrasonography is an effective and feasible tool for breast cancer screening in individuals with severe motor and intellectual disabilities.
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Neoplasias de la Mama , Discapacidad Intelectual , Femenino , Humanos , Anciano , Adulto , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/epidemiología , Mamografía , Detección Precoz del Cáncer/métodos , UltrasonografíaRESUMEN
BACKGROUND: Mucopolysaccharidosis type II (MPS II), or Hunter syndrome, is a rare X-linked metabolic disorder predominantly affecting males. Pabinafusp alfa, an iduronate-2-sulfatase enzyme designed to cross the blood-brain barrier, was approved in Japan in 2021 as the first enzyme replacement therapy targeting both the neuropathic and somatic signs and symptoms of MPS II. This study reports caregivers' experiences of MPS II patients receiving pabinafusp alfa through qualitative interviews. METHODS: Semi-structured, qualitative interviews were conducted with caregivers at seven clinical sites in Japan using a semi-structured moderation guide (Voice of the Caregiver guide). Thematic analysis was applied to the interview transcripts to identify symptoms and health-related quality of life impacts at baseline, changes during treatment, and overall treatment experience. RESULTS: Seven caregivers from 16 trial sites participated, representing seven children aged 8-18 years who had received pabinafusp alfa for 3.3-3.5 years at the time of the interviews. Data suggest a general trend toward improvement in multiple aspects, although not all caregivers observed discernible changes. Reported cognitive improvements included language skills, concentration, self-control, eye contact, mental clarity, concept understanding, following instructions, and expressing personal needs. Further changes were reported that included musculoskeletal improvements and such somatic changes as motor function, mobility, organ involvement, joint mobility, sleep patterns, and fatigue. Four caregivers reported improvements in family quality of life, five expressed treatment satisfaction, and all seven indicated a strong willingness to continue treatment of their children with pabinafusp alfa. CONCLUSION: Caregivers' perspectives in this study demonstrate treatment satisfaction and improvement in various aspects of quality of life following therapy with pabinafusp alfa. These findings enhance understanding of pabinafusp alfa's potential benefits in treating MPS II and contribute to defining MPS II-specific outcome measures for future clinical trials.
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Iduronato Sulfatasa , Mucopolisacaridosis II , Masculino , Niño , Humanos , Mucopolisacaridosis II/tratamiento farmacológico , Cuidadores/psicología , Calidad de Vida , Japón , Iduronato Sulfatasa/uso terapéutico , Terapia de Reemplazo Enzimático/métodos , Enfermedades Raras/tratamiento farmacológicoRESUMEN
Gaucher disease (GD) is a lysosomal storage disorder caused by a deficiency in the GBA1-encoded enzyme, ß-glucocerebrosidase. Enzyme replacement therapy is ineffective for neuronopathic Gaucher disease (nGD). High-dose ambroxol has been administered as an alternative treatment for a group of patients with nGD. However, little is known about the clinical indication and the long-term outcome of patients after ambroxol therapy. We herein report a case of a female patient who presented with a progressive disease of GD type 2 from 11 months of age and had the pathogenic variants of p.L483P (formerly defined as p.L444P) and p.R502H (p.R463H) in GBA1. A combined treatment of imiglucerase with ambroxol started improving the patient's motor activity in 1 week, while it kept the long-lasting effect of preventing the deteriorating phenotype for 30 months. A literature review identified 40 patients with nGD, who had received high-dose ambroxol therapy. More than 65% of these patients favorably responded to the molecular chaperone therapy, irrespective of p.L483P homozygous, heterozygous or the other genotypes. These results highlight the long-lasting effect of ambroxol-based chaperone therapy for patients with an expanding spectrum of mutations in GBA1.
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Ambroxol , Enfermedad de Gaucher , Enfermedades por Almacenamiento Lisosomal , Humanos , Femenino , Enfermedad de Gaucher/tratamiento farmacológico , Enfermedad de Gaucher/genética , Enfermedad de Gaucher/patología , Ambroxol/uso terapéutico , Terapia Combinada , Chaperonas MolecularesRESUMEN
Transitional medicine refers to the seamless continuity of medical care for patients with childhood-onset diseases as they grow into adulthood. The transition of care must be seamless in medical treatment as the patients grow and in other medical aids such as subsidies for medical expenses in the health care system. Inappropriate transitional care, either medical or social, directly causes poorer prognosis for many early-onset diseases, including primary dyslipidemia caused by genetic abnormalities. Many primary dyslipidemias are designated as intractable diseases in the Japanese health care system for specific medical aids, as having no curative treatment and requiring enormous treatment costs for lipid management and prevention of complications. However, there are problems in transitional medicine for primary dyslipidemia in Japan. As for the medical treatment system, the diagnosis rate remains low due to the shortage of specialists, their insufficient link with generalists and other field specialists, and poor linkage between pediatricians and physicians for adults. In the medical care system, there is a mismatch of diagnostic criteria of primary dyslipidemias between children and adults for medical care expense subsidization, as between The Program for the Specific Pediatric Chronic Diseases and the Program for Designated Adult Intractable Diseases. This could lead some patients subsidized in their childhood to no longer be under the coverage of the aids after transition. This review intends to describe these issues in transitional medicine of primary dyslipidemia in Japan as a part of the efforts to resolve the problems by the Committee on Primary Dyslipidemia under the Research Program on Rare and Intractable Disease of the Ministry of Health, Labour and Welfare of Japan.
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Dislipidemias , Humanos , Dislipidemias/terapia , Dislipidemias/epidemiología , Japón/epidemiología , Adulto , Transición a la Atención de Adultos , NiñoRESUMEN
BACKGROUND: Childhood-onset glomerular disease often requires ongoing treatment and follow-up into adulthood. However, few studies have analyzed the associated impact and distress experienced by patients with this condition during the transition from childhood to adolescence and adulthood. METHODS: At three facilities, we recruited patients who developed idiopathic nephrotic syndrome or IgA nephropathy during childhood and were at least 18 years old at the time of study entry. Among them, a questionnaire-based survey was administered to patients who consented to participate, and the results were analyzed in conjunction with clinical information. RESULTS: Data from a total of 38 patients were analyzed. Of these patients, 15 had idiopathic nephrotic syndrome and 23 had IgA nephropathy. The age of transition from pediatrics to the adult medicine department was correlated with the number of recurrences. Many patients also reported being significantly affected by exercise restrictions and physical decline associated with their diseases and medications. Various impacts, including distress, affected decision-making regarding higher education, with patients engaging in higher education at a significantly higher rate compared with the regional average (66.7% vs. 46.9%, p = 0.028). CONCLUSION: We analyzed the impact of childhood-onset glomerular disease and distress during the transition period from pediatric to adult care. This study highlighted the significant impact of medications and exercise restrictions on patients' decisions regarding higher education. Future prospective studies will be needed to examine patients' distress in more detail and establish management approaches to enhance patient quality of life.