Survey of medications for myelomeningocele patients over their lifetime in Japan.

BACKGROUND: This study aimed to investigate medication prescriptions for patients with myelomeningocele (MMC) across different age groups, particularly in adulthood and after middle age. METHODS: The Japan Medical Data Center (JMDC) database, based on medical claims data, was utilized for this analysis. Patients were divided into 10-year age groups, and prescriptions for analgesics, anticonvulsants, psychotropic drugs, lifestyle disease-related drugs, drugs for urinary incontinence, and laxatives were examined. To compare the differences in the utilization of medications unrelated to lifestyle-related diseases across different age groups, the data was categorized into three age groups: 19 or under, 20-39, and 40 or older. RESULTS: Among the 556 MMC patients, the percentage of those regularly prescribed analgesics increased from 2.8% in patients ≤ 19 to 31.7% in patients 40 or older (p < 0.01). Psychotropic medication use also increased with age, rising significantly from 6.3% in patients ≤ 19 to 34.6% in patients 40 or older (p < 0.01). Patients with MMC showed an increasing trend in prescriptions for lifestyle-related disease medications compared to the normal control group. Notably, the percentage of patients in their 30 s taking hypertension medication was 4.9%, significantly higher than the 0.86% in the control group (p = 0.029). In their 40 s, 22.9% of MMC patients were prescribed hyperlipidemia medication, significantly higher than the 3.9% in the control group (p < 0.01). CONCLUSION: Comprehensive multidisciplinary support and follow-up are crucial to enhance the quality of life for MMC patients, with particular attention to pain management, psychological care, and treatment of lifestyle-related diseases.

The effect of shunt removal on the quality of life in patients with congenital hydrocephalus.

BACKGROUND: Although there have been reports investigating the quality of life of patients who underwent ventriculoperitoneal shunting or endoscopic third ventriculostomy (ETV) for congenital hydrocephalus, there have been no studies of the quality of life of patients after ventriculoperitoneal shunt (VPS) removal. In the present study, a survey of pediatric and congenital hydrocephalus patients was conducted to compare the quality of life of patients with a remaining VPS with that of patients who had the shunt removed. METHODS: Between February 2020 and November 2021, an outpatient survey was administered to patients 8 years of age and older who had undergone VPS due to a diagnosis of congenital hydrocephalus. The Hydrocephalus Outcome Questionnaire (HOQ) was used to assess the quality of life for this study. The HOQ scores (overall health score, physical health score, cognitive health score, and social-emotional health score) were compared among three groups: a VPS-remaining group, VPS-removed with endoscopic third ventriculostomy (ETV) group, and VPS-removed without ETV group. RESULTS: The total number of patients who underwent VPS for hydrocephalus was 71, with 47 in the VPS-remaining group, 14 in the shunt-removed with ETV group, and 10 in the shunt-removed without ETV group. The HOQ overall health score was 0.68 for the VPS-remaining group, 0.74 for the shunt-removed with ETV group, and 0.74 for the shunt-removed without ETV. There were no significant differences between the VPS-remaining group and the VPS-removed with or without ETV groups (p = 0.3255, 0.4178, respectively). CONCLUSION: There was no significant difference in the quality of life between patients with a remaining VPS and those who had their VPS removed with or without ETV.

Current status and challenges of neurosurgical procedures for patients with myelomeningocele in real-world Japan.

BACKGROUND: Little is known about the real-world status of neurosurgical treatment of myelomeningocele patients. OBJECTIVE: To investigate the real-world status of neurosurgical treatment of myelomeningocele patients, medical claims data provided by the Japan Medical Data Center (JMDC) were analyzed. METHODS: The health claims data of 556 patients with myelomeningoceles from January 2005 to March 2020 were examined. The number of neurosurgical procedures, including myelomeningocele repair, tethered cord release, cerebrospinal fluid (CSF) shunt, CSF drainage, and endoscopic third ventriculostomy (ETV), was determined. RESULTS: A total of 313 neurosurgical procedures were performed for 135 patients in 74 institutions during the study period. The shunt survival rate was most affected by shunts that were revised when the patient was less than 1 year old, which had a significantly lower survival rate than all of the initial shunts performed when the patient was less than on1 year old; the 1-year shunt survival rate was 35 vs 64% (P = 0.0102). The survival rate was significantly lower in patients younger than 1 year who had CSF drainage before shunting compared to those younger than 1 year who did not have CSF drainage before shunting; the 1-year shunt survival rate was 27 vs 59% (P = 0.0196), and 81% of patients remained free of tethered cord release 10 years later. CONCLUSIONS: In this study, a revised shunt of less than 1 year of age and CSF drainage before shunting were the factors that lowered the shunt survival rate in the real world for CSF shunts for hydrocephalus associated with myelomeningocele.

Newborn with severe supratentorial subdural hematoma due to laceration of the tentorium cerebelli.

PURPOSE: A rare case of a newborn girl born by a normal vaginal delivery who developed a severe supratentorial subdural hematoma due to a laceration in the tentorium cerebelli is presented. METHODS AND RESULTS: The girl, born by normal vaginal delivery at 39 weeks and 4 days of gestation, showed an intermittent decrease in oxygen saturation and bulging of the anterior fontanelle. Computed tomography (CT) and magnetic resonance imaging (MRI) showed a subdural hematoma centered in the left occipital region with a midline shift. Hematoma evacuation with craniotomy was performed, and the source of bleeding was a laceration of the tentorium cerebelli. CONCLUSION: Severe supratentorial subdural hematomas can occur due to laceration of the tentorium cerebelli even in a normal vaginal delivery.

Lignans and coumarins from the stem bark of Alyxia fascicularis (Wall. ex G. Don) Benth. ex Hook. f.).

In the first phytochemical investigation of specialized metabolites from the stem bark of Alyxia fascicularis, which is used in different traditional medicines, including those of Myanmar and China, five lignans (1-5) and three coumarins (6-8) were isolated by semipreparative HPLC separations and identified mainly by 1D and 2D NMR spectral analysis. The radical scavenging activity of isolated compounds was tested using the DPPH method. Noteworthy, most lignans exhibited antiradical effects comparable to vitamin C and gallic acid. Instead, compounds 1-8 showed no cytotoxic effect on Hela cell line. A possible biosynthetic pathway to enantiomeric 3 and 4 is suggested.

Number of surgeries performed during the lifetime of patients with myelomeningocele.

OBJECTIVE: Patients with myelomeningocele often require multiple surgeries, but no study has clarified the kind of treatment given to these patients throughout their lives. The authors analyzed the type of surgery that was performed and at what age for Japanese patients with myelomeningoceles. METHODS: The Japanese health claims data of 556 patients with myelomeningocele for the period from January 2005 to March 2020 provided by the Japan Medical Data Center Co., Ltd., were examined to investigate the number of surgeries performed and the patient age at surgery for each specialty. The patients were divided into two groups (those ≤ 18 years old [group A] and those > 18 years old [group B]), and the way in which the types of surgery and the percentage of surgeries changed between these two groups was examined. RESULTS: The mean follow-up period was 4.4 years. The mean age at the end of the overall follow-up was 18.6 years (range 0-70.5 years), and 1033 surgeries were performed on 294 patients (0.42 surgeries performed per patient per year) during this period. The number of surgeries for patients in group A was 818 in 192 patients, with 0.62 surgeries per patient per year, and for patients in group B it was 215 in 102 patients, with 0.19 surgeries per patient per year. The number of surgeries and the mean age at the time of surgery were as follows: 313 neurosurgeries, 5.16 years; 280 orthopedic surgeries, 11.36 years; 70 urological surgeries, 14.57 years; and 202 dermatological/plastic surgeries, 16.19 years. In the surgeries related to myelomeningocele, the rates of CSF shunt placement, tethered cord release, muscle and tendon surgery, and other bone and joint surgery decreased significantly in group B, but they continued to undergo these surgeries. In group B, the rates of skin surgery, nephrostomy, ureterostomy, and cystostomy were significantly higher. CONCLUSIONS: A significant number of surgeries in multiple specialties related to myelomeningocele continue to be performed in adulthood, indicating that these patients require continuous care throughout their lives.

Constituents of Aegle marmelos from Myanmar.

Five compounds (1-5), including three coumarins (1-3) and two alkaloids (4,5) were isolated during the first investigation of the stem bark of Aegle marmelos (L.) Corrêa. collected in Myanmar. Their structures were determined by NMR spectra analysis. Among them, 7´-O-ethylmarmin (1) and 2-O-ethyltembamide (5) were identified as new compounds. Skimmianine (4) showed moderate cytotoxicity against a HeLa cell line, and 7´-O-ethylmarmin (1), marmin (2), and (+)-epoxyaurapten (3) displayed weak radical scavenging activity according to a DPPH scavenging assay.

Rapid deterioration of an asymptomatic lumbosacral lipoma due to formation of an extracanalicular syrinx: case report.

The authors present the case of a 1-month-old girl with a lumbosacral lipoma who then developed an extracanalicular syrinx and experienced rapid deterioration. The patient's initial MRI study, obtained before she became symptomatic, revealed a spinal lipoma with a syrinx in contact with the lipoma-cord interface. She was initially asymptomatic but developed loss of motor function in the left leg 14 days after MRI. Emergency surgery was performed. Intraoperative findings revealed a swollen spinal cord. Lipomatous tissue on the caudal side of the conus was removed subtotally, and the central canal was opened. Expansion of the syrinx was observed intraoperatively. Postoperatively, the patient's left leg paresis remained. Postoperative MRI revealed rostral and extracanalicular expansion of the syrinx. This is the first report on the rapid deterioration of a conus lipoma due to extracanalicular expansion of a syrinx. Careful follow-up and repeat MRI should be considered for patients with spinal lipomas with syringomyelia, especially when the syrinx is attached to the lipoma-cord interface.

Comparative Study of Biological Activities of Venom from Colubrid Snakes Rhabdophis tigrinus (Yamakagashi) and Rhabdophis lateralis.

Rhabdophis lateralis, a colubrid snake distributed throughout the continent of Asia, has recently undergone taxonomic revisions. Previously, Rhabdophis lateralis was classified as a subspecies of R. tigrinus (Yamakagashi) until 2012, when several genetic differences were discovered which classified this snake as its own species. To elucidate the toxicity of venom from this poorly studied colubrid, various biological activities were compared between the venom from the two snake species. The components of their venom were compared by the elution profiles of reversed-phase HPLC and SDS-PAGE, and gel filtrated fractions were tested for effects on blood coagulation. Proteolytic activities of these fractions were also assayed by using synthetic substrates, fibrinogen, and matrix proteins. Similar to the R. tigrinus venom, the higher molecular weight fraction of R. lateralis venom contained a prothrombin activator. Both prothrombin time (PT) and activated partial thromboplastin time (APTT) of human plasma were shortened by the addition of R. lateralis and R. tigrinus venom. The thrombin formation was estimated by the uses of SDS-PAGE and chromogenic substrates. These venom fractions also possessed very specific proteinase activity on human fibrinogen, but the substrates for matrix metalloproteinase, such as collagen and laminin, were not hydrolyzed. However, there were some notable differences in reactivity to synthetic substrates for matrix metalloproteinase, and R. tigrinus venom possessed relatively higher activity. Our chemical investigation indicates that the components included in both venoms resemble each other closely. However, the ratio of components and proteolytic activity of some ingredients are slightly different, indicating differences between two closely-related snakes.

Enlarging pediatric ectopic Rathke's cleft cyst in the prepontine cistern: case report.

Rathke's cleft cyst is a cystic disease that occurs in the sella turcica or, occasionally, in the suprasellar area. An ectopic Rathke's cleft cyst is extremely rare, and its nature is less well understood. The authors report the case of a 14-year-old girl who presented with a growing cystic lesion in the prepontine cistern, immediately behind the dorsum sellae. Preoperative imaging and intraoperative investigation showed part of the cyst wall continuing into the dorsum sellae, to the pituitary gland. The cisternal portion of the cyst wall was totally resected via a right subtemporal approach. Histopathological examination of the cyst wall showed a monolayer of ciliated cells, identical to those of Rathke's cleft cyst. To the best of the authors' knowledge, this represents the first pediatric case of Rathke's cleft cyst occurring in the prepontine cistern.

5-ALA fluorescence-guided endoscopic surgery for mixed germ cell tumors.

5-Aminolevulinic acid (5-ALA) fluorescence-guided surgery is widely used for detection and planning of resection of malignant gliomas and other brain tumors. However, no reports have described 5-ALA fluorescence-guided surgery or direct visualization of germ cell tumors. Here, we report two cases of germ cell tumors in which a positive 5-ALA fluorescent signal was visualized with a neuroendoscope. Both cases had a tumor in the pineal region that was associated with hydrocephalus. The patients underwent surgery after administration of 5-ALA. After ventricular puncture of the anterior horn, we could observe the ventricular wall and tumor using the Karl Storz Photodynamic diagnosis system endoscope. Then, biopsy of the pineal tumor and endoscopic third ventriculostomy were performed in both cases. In case 1, a 22-year-old man, part of the ventricular wall and tumor tissue showed red fluorescence. In case 2, a 16-year-old man, part of the fornix and infundibular recess showed red fluorescence, and the tumor showed relatively weak red fluorescence. The histopathological diagnosis of both cases was pure germinoma. This is the first report of direct visualization of mixed germinomas with 5-ALA fluorescence-guided endoscopic surgery. This method not only allows visualization of the tumor mass, but may also be useful for detailed observation in the ventricular wall.

Okinalysin, a novel P-I metalloproteinase from Ovophis okinavensis: biological properties and effect on vascular endothelial cells.

A novel hemorrhagic metalloproteinase, okinalysin, was isolated from the venom of Ovophis okinavensis. It possessed caseinolytic and hemorrhagic activities, and also hydrolyzed fibrinogen and collagen. These activities were inhibited by ethylenediaminetetraacetic acid (EDTA) but not by p-amidinophenyl methanesulfonyl fluoride hydrochloride (APMSF). The molecular mass of okinalysin was 22,202 Da measured by MALDI/TOF mass spectrometry. The primary structure of okinalysin was partially determined by Edman sequencing, and the putative zinc-binding domain HEXXHXXGXXH was found to be present in its structure. From these data, okinalysin is defined as a metalloproteinase belonging to a P-I class. The partial amino acid sequence of okinalysin was homologous to the C-terminus of MP 10, a putative metalloproteinase induced from transcriptome of the venom gland cDNA sequencing of O. okinavensis. Okinalysin possessed cytotoxic activity on cultured endothelial cells, and the EC50 on human pulmonary artery endothelial cells was determined to be 0.6 µg/mL. The histopathological study also showed that okinalysin causes the leakage of red blood cells and neutrophil infiltration. These results indicate that destruction of blood vessels by okinalysin is one of the main causes of hemorrhage.

Characterization and identification of partial amino acid sequence of a novel elastase inhibitor, Asnidin from Aspergillus nidulans.

A novel elastase inhibitor from Aspergillus nidulans NBRC 4340, Asnidin, was isolated, and biochemical properties and partial amino acid sequence were examined. Column chromatography using diethylaminoethyl (DE) 52-Cellulose and reversed-phase HPLC were used to purify the inhibitor. Purified Asnidin was found to be homogeneous as indicated by reversed-phase HPLC and TOF-MS (Time of Flight Mass Spectrometry). Asnidin has a molecular weight of 4,181.63 as determined by TOF-MS. The elastolytic activities of elastases from A. fumigatus, A. flavus, and human leukocytes but not chymotrypsin, and elastases from snake venom and bacteria were inhibited by Asnidin. The fibrinogenase and collagen type IV hydrolytic activities of the elastase from A. fumigatus were inhibited by Asnidin. Asnidin was found to be stable under heat treatment and over a wide pH range. The elastolytic inhibitory activity of Asnidin was inhibited by dithiothreitol (DTT), while no inhibition was observed with ethylenediaminetetraacetic acid (EDTA-2Na) and benzamidine. Since there is a possibility of Asnidin becoming another drug in the arsenal of weapons against aspergillosis or interstitial pneumonia, further studies are warranted.

Isolation and biochemical characterization of rubelase, a non-hemorrhagic elastase from Crotalus ruber ruber (Red Rattlesnake) venom.

A novel non-hemorrhagic basic metalloprotease, rubelase, was isolated from the venom of Crotalus ruber ruber. Rubelase hydrolyzes succinyl-L-alanyl-L-alanyl-L-alanyl p-nitroanilide (STANA), a specific substrate for elastase, and the hydrolytic activity was inhibited by chelating agents. It also hydrolyzes collagen and fibrinogen. However, hemorrhagic activity was not observed. By ESI/Q-TOF and MALDI/TOF mass spectrometry combined with Edman sequencing procedure, the molecular mass of rubelase was determined to be 23,266 Da. Although its primary structure was similar to rubelysin (HT-2), a hemorrhagic metalloprotease isolated from the same snake venom, the circumstances surrounding putative zinc binding domain HEXXHXXGXXH were found to be different when the three-dimensional computer models of both metalloproteases were compared. The cytotoxic effects of rubelase and rubelysin on cultured endothelial and smooth muscle cells were also different, indicating that the substitution of several amino acid residues causes the changes of active-site conformation and cell preference.

High-yields heterologous production of the novel Aspergillus fumigatus elastase inhibitor AFUEI in Aspergillus oryzae.

AFUEI, an elastase inhibitor produced by Aspergillus fumigatus strongly inhibits the elastolytic activity of A. fumigatus etc. To purify AFUEI, we constructed a strain that overproduces AFUEI by introducing the gene encoding AFUEI (Genbank accession no. AB546725) under control of the amyB promoter into the heterologous host Aspergillus oryzae. A. oryzae TF-4 displayed strong elastase inhibitory activity and produced considerably more AFUEI than that of A. fumigatus. Furthermore, AFUEI could be purified using culture broth and single ultrafiltration (UF) treatment, allowing for the effective production of AFUEI for use in clinical trials.

Biological and pathological studies of rosmarinic acid as an inhibitor of hemorrhagic Trimeresurus flavoviridis (habu) venom.

In our previous report, rosmarinic acid (RA) was revealed to be an antidote active compound in Argusia argentea (family: Boraginaceae). The plant is locally used in Okinawa in Japan as an antidote for poisoning from snake venom, Trimeresurus flavoviridis (habu). This article presents mechanistic evidence of RA's neutralization of the hemorrhagic effects of snake venom. Anti-hemorrhagic activity was assayed by using several kinds of snake venom. Inhibition against fibrinogen hydrolytic and collagen hydrolytic activities of T. flavoviridis venom were examined by SDS-PAGE. A histopathological study was done by microscopy after administration of venom in the presence or absence of RA. RA was found to markedly neutralize venom-induced hemorrhage, fibrinogenolysis, cytotoxicity and digestion of type IV collagen activity. Moreover, RA inhibited both hemorrhage and neutrophil infiltrations caused by T. flavoviridis venom in pathology sections. These results demonstrate that RA inhibited most of the hemorrhage effects of venom. These findings indicate that rosmarinic acid can be expected to provide therapeutic benefits in neutralization of snake venom accompanied by heat stability.

Comparison of sea snake (Hydrophiidae) neurotoxin to cobra (Naja) neurotoxin.

Both sea snakes and cobras have venoms containing postsynaptic neurotoxins. Comparison of the primary structures indicates many similarities, especially the positions of the four disulfide bonds. However, detailed examination reveals differences in several amino acid residues. Amino acid sequences of sea snake neurotoxins were determined, and then compared to cobra neurotoxins by computer modeling. This allowed for easy comparison of the similarities and differences between the two types of postsynaptic neurotoxins. Comparison of computer models for the toxins of sea snakes and cobra will reveal the three dimensional difference of the toxins much clearer than the amino acid sequence alone.

Isolation and chemical characterization of a toxin isolated from the venom of the sea snake, Hydrophis torquatus aagardi.

Sea snakes (family: Hydrophiidae) are serpents found in the coastal areas of the Indian and Pacific Oceans. There are two subfamilies in Hydrophiidae: Hydrophiinae and Laticaudinae. A toxin, aagardi toxin, was isolated from the venom of the Hydrophiinae snake, Hydrophis torquatus aagardi and its chemical properties such as molecular weight, isoelectric point, importance of disulfide bonds, lack of enzymatic activity and amino acid sequence were determined. The amino acid sequence indicated a close relationship to the primary structure of other Hydrophiinae toxins and a significant difference from Laticaudinae toxins, confirming that primary toxin structure is closely related to sea snake phylogenecity.

Biological properties of elastase inhibitor, AFLEI from Aspergillus flavus.

The biological properties of elastase inhibitor from Aspergillus flavus (AFLEI) were investigated. AFLEI was produced at the highest rate when casamino acid was used as the nitrogen source. When a mixture of AFLEI (approx. molecular weight, 7,500) and elastase from A. flavus (approx. molecular weight, 40,000) was detected using anti-AFLEI antibody, molecular weight of the detected mixture was approximately 48,000, indicating that AFLEI and elastase bound at a proportion of 1 : 1. When immunocompromised mice administrered of immunosuppressive (cyclophosphamide) were infected by inhalation of A. flavus and administered amphotericin B (AMB) alone or in combination with AFLEI, survival rate tended to be higher with combination treatment than with AMB alone. Moreover, although extensive bleeding was seen in pathology sections taken from rat lung resected 24 hr after purified elastase was administered to the lung via the bronchus, this bleeding was inhibited by AFLEI. These findings indicate that for the treatment of aspergillosis, combination of an existing antifungal agent with AFLEI can be expected to provide greater therapeutic benefits than administration of an antifungal agent alone.

A novel low molecular weight hemorrhagic toxin from Trimeresurus flavoviridis (Vorojima) venom.

A low molecular weight hemorrhagic toxin, LMHT, was isolated from the venom of Trimeresurus flavoviridis from Yorojima using Q-Sepharose column chromatography. The purified hemorrhagic toxin was homogeneous by disc polyacrylamide gel electrophoresis at pH 8.3, and Ouchterlony immunodiffusion. LMHT has a molecular weight of 16,500 and possesses hemorrhagic activity. It did not show casein, azocasein, azoalbumin, or TAME (tosyl-L-arginine methyl ester hydrochloride) hydrolytic activities. Hemorrhagic activity was inhibited by EDTA, TEP (tetraethylenepentamine), p-APMSF(p-amidinophenylmethanesulfonylfluoride HCl), and N-bromosuccinimide. The minimum hemorrhagic dose of this hemorrhagic toxin was 7.1 microg/mouse. LMHT induced hydrolysis of the Aa and Bbeta chains of bovine fibrinogen.