Kinetics and mechanism of the hydrolysis of a 2-substituted imidazoline, cibenzoline (cifenline)

The results of a kinetic and mechanistic study of the hydrolysis of a new antiarrhythmic agent, cibenzoline, are reported. The reaction is subject to specific base catalysis which proceeds via the protonated cibenzolinium ion. No evidence for the existence of a "pseudobase"-type intermediate could be found. The results support only one of two different mechanisms which have been proposed previously for the hydrolysis of this class of compounds.     

Isolation and partial characterization of neurofibrillary tangles and amyloid plaque core in Alzheimer's disease: immunohistological studies

Fractions enriched in neurofibrillary tangles (NFT) and amyloid fibrils were isolated from the cerebral cortex of three cases of senile dementia of the Alzheimer type. Distilled water suspensions of these fractions were excluded from all pore size gels and resisted digestion with various proteolytic enzymes. Formic acid/chloroform treatment of each fraction resulted in the appearance of 4,000-6,000, 15,000-17,000 and 24,000 molecular weight proteins, with concomitant diminution in the amount of excluded material at the top of each gel. The 4,000-6,000 dalton band was best seen in fractions containing randomly arranged amyloid fibrils, and its amino acid composition resembled that of the recently reported "beta" protein. A polyclonal antiserum to purified NFT reacted with tangles in neurons and in dystrophic neurites around plaques by immunoperoxidase staining. No reaction was obtained with cerebrovascular or plaque core amyloid immunohistologically, or with the 4-6 kD protein on immunoblots. Cross-reactivity with the neurofibrillary lesions occurring in Pick's disease, progressive supranuclear palsy, postencephalitic Parkinsonism and dementia pugilistica was also seen. Specific binding of this antiserum to the double filamentous structure was confirmed by immunoelectron microscopy. Although the presence of "beta" protein in both NFT and amyloid-containing fractions suggests that it may be an important constituent of both, cross-contamination cannot be excluded.     

Characteristics affecting cervical sagittal alignment in patients with chronic low back pain

BackgroundSagittal spino-pelvic malalignment in patients with chronic low back pain (CLBP) have been reported in the past, which may also affect cervical spine lesions. The purpose of this study is to investigate the cervical alignment in patients with CLBP.MethodOf the patients who visited an orthopedic specialist due to low back pain lasting more than three months, 121 cases (average 71.5-years-old, 46 male and 75 female) with whole standing spinal screening radiographs were reviewed (CLBP group). Cervical parameters included cervical lordosis (CL), C2–C7 sagittal vertical axis (C2-7 SVA), and the T1 slope minus CL (T1S-CL). Cervical spine deformity was defined as C2-7 SVA >4 cm, CL <0°, or T1S-CL ≧20°. We compared the cervical alignment of these patients with 121 age and gender matched volunteers (control group).ResultsThe prevalence of cervical spine deformity was significantly higher in the CLBP group than in the control group (20.7% vs. 10.7%, P = 0.034). The mean CL was smaller in the CLBP group than in the control group (16.1° vs. 21.4°, P = 0.002). The mean C2-7 SVA was 17.6 mm vs. 18.7 mm in the CLBP group and in the control group, respectively (P = 0.817). The mean T1S-CL was larger in the CLBP group than in the control group (9.1° vs. 3.5°, P < 0.001). Multivariate analysis showed that people with CLBP were more likely to have cervical deformities than people without CLBP (odds ratio 2.16, 95% confidence interval 1.006 to 4.637).ConclusionsThis study results suggest that people with CLBP present with worse cervical sagittal alignment and higher prevalence of cervical spine deformities than age and gender matched volunteers with no CLBP. This means CLBP impacts cervical spine lesions negatively.Level of evidenceⅣ     

Lessons learned from lower urinary tract complications of anorectoplasty for imperforate anus with rectourethral/rectovesical fistula: Laparoscopy-assisted versus posterior sagittal approaches

PurposeTo report the sequelae of and preventive strategies for selected lower urinary tract (LUT) complications, i.e., posterior urethral diverticulum (PUD), intraoperative LUT injuries, postoperative dysuria, and fistula recurrence in male imperforate anus (IA) with rectourethral/rectovesical (RU/RV) fistula after laparoscopy-assisted anorectoplasty (LAARP) or posterior sagittal anorectoplasty (PSARP).Methods153 boys with IA and RU/RV fistula treated 1986–2019 by LAARP (n = 56) or PSARP (n = 97) at two unrelated institutes were studied retrospectively.ResultsAfter mean follow-up of 17.0 years (range: 36.5 days-32.0 years), the overall incidences of LUT complications were: LAARP (6/56; 10.7%); PSARP (7/97; 7.2%); p = 0.55, comprising PUD: LAARP (n = 5), PSARP (n = 0); p = 0.006; injuries: LAARP (n = 0), PSARP (n = 5); p = 0.16; dysuria: LAARP (n = 1), PSARP (n = 1); p>0.999; and recurrence: LAARP (n = 0), PSARP (n = 1); p>0.999. Mean onset of PUD was 5.1 years (range: 1.0–15.1 years). Treatment: PUD: surgery (n = 2/5), conservative (n = 3/5); injuries: intraoperative repair (n = 5/5); dysuria: conservative (n = 2/2), and recurrence: redo PSARP (n = 1/1).ConclusionsStrategies devised to improve dissection accuracy resolved the specific technical issues causing LUT complications (remnant RU fistula dissection in LAARP and blind posterior access in PSARP). Currently, the incidence of new cases of PUD and LUT injuries is zero.Level of Evidence: Level III     

Peliosis Hepatis in a Child with X-Linked Myotubular Myopathy Treated with Living-Donor Liver Transplant: A Case Report

BackgroundMyotubular myopathy is a rare disease sometimes accompanied by peliosis hepatis, a leading cause of fatal liver hemorrhage.Case ReportWe present a case of a 2-year-old boy with myotubular myopathy who developed liver hemorrhage because of peliosis hepatis and was successfully treated with living-donor liver transplant. The patient initially presented with fever, anemia, and liver dysfunction. A computed tomographic scan revealed hemorrhages in the liver, and the patient underwent hepatic artery embolization twice. After the second embolization, multiple peliosis hepatis cavities appeared in the left lobe of the liver that had increased in size. Therefore, the patient underwent ABO-incompatible living-donor liver transplant using a lateral segment graft from his father. The patient developed severe septic shock with an unknown focus on postoperative day 18, which resolved with antibiotic therapy. On postoperative day 62, he was discharged. Fourteen months after undergoing living-donor liver transplant, the patient showed no recurrence of peliosis hepatis.ConclusionsAlthough the long-term prognosis of peliosis hepatis due to myotubular myopathy after living-donor liver transplant remains unclear, liver transplant may be a curative treatment for patients with myotubular myopathy who have uncontrollable peliosis hepatis.     

Efficacy and safety of holmium laser enucleation of the prostate for elderly patients: surgical outcomes and King’s Health Questionnaire

BackgroundHolmium laser enucleation of the prostate (HoLEP) has been a widely utilized minimally invasive surgical procedure for benign prostate hyperplasia. The current study aimed to compare surgical outcomes and King’s Health Questionnaire (KHQ) assessment scores following HoLEP between younger men and those aged ≥75 years.MethodsThis prospective single-center study compared perioperative complications, postoperative urinary conditions, and KHQ scores (nine categories) between men aged ≥75 years (group A) and men aged <75 years (group B) before and 1, 3, and 6 months after surgery.ResultsA total of 100 patients were included for analysis (group A, n=38 and group B, n=62). No differences in patient backgrounds, perioperative complications, such as perioperative decrease in hemoglobin, postoperative fever, postoperative indwelling catheterization duration, or postoperative hospitalization duration, and KHQ were observed between both groups. Both groups showed significantly better International Prostate Symptom Scores, quality of life, maximum urinary flow rate, and postvoid residual volume 1, 3, and 6 months after HoLEP compared to their respective preoperative levels (P<0.01). Regarding KHQ categories, both groups showed significantly better general health perceptions, impact on life, emotions, and sleep/energy 1 month after HoLEP; role limitations, physical limitations, and social limitations 3 months after HoLEP; and personal relationships and incontinence severity measures 6 months after HoLEP compared to their respective preoperative levels (P<0.05).ConclusionsHoLEP could be safe and effective even for men aged ≥75 years, comparing complications, urinary condition, and KHQ scores.     

Isolated avulsion fracture of the lesser tuberosity of the humerus: A case report

Isolated avulsion fractures of the lesser tuberosity are extremely rare. A 24-year-old woman fell on her back as her arm was forcibly extended and adducted. Radiographs revealed a small fragment of bone beneath the glenoid. Axillary radiography showed the bone fragment and a bone defect of the lesser tuberosity. Computed tomography scan clearly demonstrated those findings. Surgery was performed 3 weeks after the occurrence of the injury. The bone fragment was reduced and fixed by means of two screws. After 3 weeks, light exercise was started. At follow-up 7 months later she had no complaints. Most reported cases involved sudden contraction of the subscapularis tendon. This type of fracture is sometimes misdiagnosed; computed tomography scan is useful for diagnosis. Previously reported cases have similarly demonstrated a good outcome after surgery, except in cases involving children.     

Estrogenic potential of certain pyrethroid compounds in the MCF-7 human breast carcinoma cell line

Estrogens, whether natural or synthetic, clearly influence reproductive development, senescence, and carcinogenesis. Pyrethroid insecticides are now the most widely used agents for indoor pest control, providing potential for human exposure. Using the MCF-7 human breast carcinoma cell line, we studied the estrogenic potential of several synthetic pyrethroid compounds in vitro using pS2 mRNA levels as the end point. We tested sumithrin, fenvalerate, d-trans allethrin, and permethrin. Nanomolar concentrations of either sumithrin or fenvalerate were sufficient to increase pS2 expression slightly above basal levels. At micromolar concentrations, these two pyrethroid compounds induced pS2 expression to levels comparable to those elicited by 10 nM 17ss-estradiol (fivefold). The estrogenic activity of sumithrin was abolished with co-treatment with an antiestrogen (ICI 164,384), whereas estrogenic activity of fenvalerate was not significantly diminished with antiestrogen co-treatment. In addition, both sumithrin and fenvalerate were able to induce cell proliferation of MCF-7 cells in a dose-response fashion. Neither permethrin nor d-trans allethrin affected pS2 expression. Permethrin had a noticeable effect on cell proliferation at 100 microM, whereas d-trans allethrin slightly induced MCF-7 cell proliferation at 10 microM, but was toxic at higher concentrations. Overall, our studies imply that each pyrethroid compound is unique in its ability to influence several cellular pathways. These findings suggest that pyrethroids should be considered to be hormone disruptors, and their potential to affect endocrine function in humans and wildlife should be investigated.