Minimum-Dose,Short-Term Methotrexate With Tacrolimus for Graft-vs-Host Disease Prophylaxis Following Unrelated Cord Blood Transplantation in Adults: A Retrospective Analysis at a Single Institution

BackgroundMethotrexate (MTX) or mycophenolate mofetil with tacrolimus (TAC) is used for graft-vs-host disease (GVHD) prophylaxis in unrelated cord blood transplantation (CBT). However, there is no consensus regimen for GVHD prophylaxis in CBT. We aimed to assess the efficacy and feasibility of minimum-dose, short-term MTX (MS-MTX) for GVHD prophylaxis in CBT.MethodsWe retrospectively evaluated 35 consecutive adult patients who underwent CBT and received MS-MTX (6 mg/m² day 1; 3 mg/m² days 3 and 6, intravenously) with TAC for GVHD prophylaxis in our hospital between 2015 and 2019. Transplantation outcomes with respect to time to hematopoietic recovery, engraftment, incidence and severity of GVHD, adverse events, relapse, nonrelapse mortality (NRM), and overall survival were evaluated.ResultsThe median time to neutrophil, platelet, and reticulocyte recovery was 22, 38, and 32 days, respectively. Cumulative neutrophil engraftment was 91.4%. After a median 3.2-year follow-up, the 2-year overall survival was 64.3%. The 2-year cumulative incidence of relapse and NRM was 20.4% and 14.9%, respectively. The 100-day cumulative incidence of grade II-IV acute GVHD and 2-year cumulative incidence of chronic GVHD were 28.6% and 36.6%, respectively. No grade IV acute GVHD was observed. Sixteen patients experienced oral mucositis and/or pharyngeal pain (46%; grades 1-2, n = 15; grade 3 pharyngeal pain, n = 1). No patients suffered from human herpesvirus 6 encephalitis/myelitis.ConclusionsMS-MTX with TAC is feasible and safe and yields lower rates of severe oropharyngeal mucositis and human herpesvirus 6 encephalitis/myelitis without increasing GVHD, graft failure, relapse, or NRM.     

Use of the sandwich method with an ultra-high-molecular-weight polyethylene prosthesis and Marlex mesh in sternal reconstruction: Report of a case

A 52-year-old Japanese man with a slow-growing chondroma originating from the sternal bone was referred to our hospital. A subtotal resection of the sternum was performed, hereafter termed the sandwich method, and an originally designed prosthesis made from ultra-high-molecular-weight polyethylene and Marlex mesh was used for reconstruction. The postoperative course was uneventful without any symptoms due to paradoxical movement of the chest or regional abscess, and no disturbance in the movement of the upper limbs, such as a surgical sequelae, was observed.     

The role of vitrectomy in rhegmatogenous retinal detachment

Several conditions, such as detachment from posterior breaks or detachment with significant media opacities, may warrant vitrectomy as the primary procedure. In cases in which the preoperative retinal view is clear and a posterior break is definitively excluded, vitrectomy does not appear to offer significant advantage over scleral buckling other than a theoretically improved ability to examine the retina microscopically with scleral depression. Performing a vitrectomy for an uncomplicated retinal detachment from a small peripheral break in which scleral buckling would be the usual procedure of choice remains controversial. Although it may avoid the complications of scleral buckling, vitrectomy does have its own potential complications. The status of the lens, cornea, and configuration of the retinal tears and detachment should carefully be considered before vitrectomy. Proper patient selection and appropriate education are important factors in a successful outcome. Finally, from an economic viewpoint, the likelihood of success with vitrectomy in one procedure compared with other less expensive procedures should be considered.     

Functional MRI of the human brain responses to olfactory stimulation

Image artifacts such as signal loss or distortion due to intravoxel phase dispersion at the skull base are problematic in analysis by functional MRI (fMRI). Since the olfactory center of the brain is located in the medial temporal and basal frontal areas, it is a challenge to try to detect the Blood Oxygenation Level Dependent (BOLD) effect during fMRI at olfactory stimulation. We examined 20 normal volunteers with a 1.5-T MR system, employing multishot, interleaved echo-planar imaging (EPI). Olfactory stimulation was performed with 2-methyl-1, 3-cyclo-pentanedione, a caramel-like fragrance, by presenting it for 20 seconds with two cycles of rest-stimulus paradigm. Sites of functional activation were identified by correlation analysis with a threshold of p < 0.01. Most commonly activated areas were the orbitofrontal and primary olfactory cortices. Mild activation was also observed in the cingulate gyrus, lateral temporal cortex, cerebellum, parietal and occipital lobes. These results indicate that olfactory stimulation participates in the emotion and behavior processes. Interestingly, broad activation in the "silent" area of the frontal and temporal lobe was also observed in some cases. Multishot EPI was a useful method to evaluate brain activation at the basal level on fMRI.     

Increase in the advanced glycation end product pentosidine in Bruch's membrane with age

PURPOSE: To determine whether there is an age-related increase of pentosidine in human Bruch's membranes and to localize pentosidine and carboxymethyllysine (CML), two well-characterized, advanced glycation end products (AGEs) in aged human Bruch's membranes and choroid in vivo. METHODS: Human Bruch's membrane samples were isolated from the retinal pigment epithelium (RPE) and choroid and subjected to reversed-phase high-performance liquid chromatography to determine pentosidine content. A polyclonal anti-pentosidine antibody and a monoclonal antibody specific for carboxymethyllysine were used to localize AGEs in 20-month-old nondiabetic, 82-year-old nondiabetic, and 82-year-old diabetic globes. RESULTS: Human Bruch's membranes (n = 20) showed a linear age-dependent increase in pentosidine that reached approximately 0.17 millimoles pentosidine per mole hydroxyproline in late life (r = 0.896; P < 0.001). Immunohistochemical evaluation showed evidence of pentosidine in Bruch's membrane, choroidal extracellular matrix, and vessel walls in the 82-year-old nondiabetic and diabetic globes. A similar staining pattern was found with the anti-CML antibody. Basal laminar deposits and drusen stained with both antibodies in the elderly nondiabetic eye. In contrast, neither antibody stained the 20-month-old tissue. CONCLUSIONS: We provide biochemical and immunohistochemical evidence for the formation of pentosidine and CML structures in human Bruch's membrane and choroid with age. These changes could promote aging of the RPE-Bruch's membrane-choroid complex.     

Effect of oral contraceptives on urinary porphyrins

Several studies have reported on the appearance of cutaneous porphyria in people treated with estrogen. This study was undertaken to investigate the effects of oral contraceptives (OCs) on levels of porphyrins in urine in nonporphyric women. 30 women aged 21-40 and on OCs were observed as the study group, and 10 women using other contraceptive methods were observed as the control group. Urinary porphyrins were measured by the Remington method. Levels of urinary coproporphyrin and of urinary uroporphyrin were higher in the study group than in the control group. These differences, however, are not statistically significant. To study the effect of duration of OC treatment, women who had taken OCs for 3-6 months and women who had taken OCs for longer than 6 months were observed, and the means of urinary coproporphyrin and uroporphyrin measured. Again, the differences were found to be insignificant, although slightly higher values of urinary coproporphyrin were obtained for women who had been on OCs for a longer period. These results compare favorably with others reported in the published literature. It can be concluded that OC treatment has no significant bearing on porphyrin metabolism.     

Multiple primary left ventricular myxomas with multiple intraventricular recurrences.

A 23-year-old male was operated on for two primary left ventricular myxomas of the "complex" type. Ten months later, abnormal echo reappeared and reoperation was carried out to excise 2 recurrent myxomas in the left ventricle. Multiple foci were most likely responsible for the recurrence. No recurrence has been detected for 20 months postoperatively. This may be the first reported case of multiple primary left ventricular myxoma with multiple recurrences in the left ventricular cavity.     

Radiographic Diagnosis of Early Colorectal Cancer, with Special Reference to the Superficial Type of Invasive Carcinoma

The possibility of radiographically diagnosing carcinoma with submucosal involvement (invasive carcinoma) is discussed based on 119 invasive carcinomas of the large bowel that had been treated surgically and colonoscopically over a period of 9 years (1989—1997) at the Cancer Institute Hospital in Tokyo. Of these lesions, 38 were superficial-type invasive carcinoma, accounting for 31.9% (38/119) of all invasive colorectal carcinomas, including 36 lesions (94.7%, 36/38) of types IIa and IIa+IIc and 2 lesions (5.3%, 2/38) of type IIc+IIa. No pure type IIc was seen. The radiographic images obtained were correlated with macroscopic findings and analyzed in terms of visualization of the lesion's contour, central depression, converging folds, and basal indentation. A definitive diagnosis of superficial invasive carcinoma can be made radiographically if a lesion measures 10 mm and reveals moderate to severe basal indentation in a complete or nearly complete profile radiographic image. Attention should be paid to the presence of superficial-type advanced carcinomas measuring 10 mm or less, which is not infrequently experienced in Japan. Polypoid invasive carcinoma can be definitively diagnosed in the same way with much more certainty than can the superficial type because few polypoid advanced carcinomas are less than 20 mm. The size and the radiographic sign of the basal indentation are the most important indicators for the diagnosis of invasive carcinoma. E-pub: 27 July 2000     

The prognostic and therapeutic relevance of p27kip1 in Ewing's family tumors.

PURPOSE: Ewing's family tumors (EFTs) display the characteristic fusion gene EWS-Fli1. We have reported EWS-Fli1 may promote the cell cycle progression accompanied by the suppression of the expression of cyclin-dependent kinase inhibitor p27(kip1) in EFT cells. Here, we describe the prognostic and therapeutic relevance of p27 in EFTs. EXPERIMENTAL DESIGN: We examined tumor samples taken from 21 patients with primary EFTs for the expression of p27 protein immunohistochemically and evaluated its correlation with clinical outcome. We also investigated the usefulness of p27 as a therapeutic strategy in vitro and in vivo using p27 expression adenovirus. Finally, we examined the process of EWS-Fli1-mediated reduction of p27 expression. RESULTS: Immunohistochemical analysis showed that a low expression level of p27 protein was related to poor event-free survival in an univariate analysis and that the expression level of p27 correlated more significantly with patient survival than several clinical factors in a multivariate survival analysis. Overexpression of p27 with the adenoviral vector remarkably inhibited the cell growth in all EFT cells tested and further induced apoptosis in the wild-type p53 EFT cells. In vivo studies demonstrated a reduction in tumor growth of EFT xenograft in nude mice treated with the intratumoral injection of p27-expressing adenovirus. EWS-Fli1 did not significantly affect the p27 promoter activity and p27 mRNA levels. However, the challenge of the proteasome inhibitor caused accumulation of p27 protein in EFT cells. These data strongly suggest EWS-Fli1 might attenuate p27 protein level via activation of the proteasome-mediated degradation pathway. CONCLUSIONS: Our findings provide the first evidence of the prognostic relevance of p27 expression in EFTs. We propose p27 as a novel and powerful therapeutic factor for the molecular target therapy of EFTs.