A pilot study of bortezomib in Korean patients with relapsed or refractory myeloma

Recent clinical trials showed that bortezomib, a novel proteasome inhibitor, had therapeutic activity in multiple myeloma. However, there was no data about the feasibility of bortezomib in Korean patients. We performed a pilot study of bortezomib in patients with relapsed or refractory myeloma (1.3 mg/m2 twice weekly for 2 week in a 3-week cycle). Seven patients were enrolled. The median age of patients was 59 yr. All patients previously received VAD (vincristine, doxorubicin and dexamethasone) and thalidomide chemotherapy. Three patients previously received alkylator-containing chemotherapy and 4 patients, autologous stem cell transplantation. Bortezomib monotherapy resulted in 3 partial remissions (43%), 3 no changes (43%) and 1 progressive disease (14%). One patient who had no response to bortezomib monotherapy experienced partial remission after addition of dexamethasone to bortezomib. The most common serious toxicity was thrombocytopenia (grade 3/4, 10 of 20 cycles (50%)) and grade 3 peripheral neuropathy was developed in 2 of 20 cycles (10%). Drug-related adverse event led to discontinuation of bortezomib in 1 patient. There was no treatment related mortality. Overall, bortezomib seems to be effective and feasible. Conduction of larger clinical studies on Korean patients is necessary to characterize clinical efficacy and safety of bortezomib more precisely.     

BK polyomavirus interstitial nephritis in a renal allograft recipient

Human polyomavirus (PV) interstitial nephritis has recently been recognized as a cause of severe renal allograft dysfunction. It occurs in immunosuppressed patients after reactivation of the latent virus PV type BK (BK virus) in the renal epithelium. BK disease is defined as a morphologically manifest renal infection with cytopathic signs accompanied by varying degrees of interstitial inflammatory cell infiltrates and functional impairment. It is also identified by the presence of cells containing viral inclusion bodies (decoy cells) in the urine. The authors report a case of BK PV interstitial nephritis in a 36-year-old renal allograft recipient. Under light microscopy the chief diagnostic indicator was detection of intranuclear viral inclusions, which were found exclusively in tubular epithelial cells. Cells with viral changes were often enlarged with nuclear atypia and chromatin basophilia. Widespread interstitial plasma cell infiltrates associated with tubulitis were present. Intranuclear paracrystalline arrays of virus particles 35-38 nm in diameter were present as characteristic ultrastructural indicators. Urine samples revealed decoy cells with ground-glass-type intranuclear inclusions positive for BK virus by electron microcopy.     

Effect of ultraviolet light on the expression of adhesion molecules and T lymphocyte adhesion to human dermal microvascular endothelial cells

In order to determine the effect of ultraviolet radiation (UVR) on the cell adhesion molecules expressed in human dermal microvascular endothelial cells (HDMEC), the cells were exposed to varying UVR doses and the cell surface was examined for expression of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM- 1), and E-selectin. The effect of UVB irradiation on the binding of T lymphocytes to HDMEC was also examined. UVA irradiation did not affect the surface expression of ICAM-1, VCAM-1, or E-selectin on the HDMEC. However, following UVB exposure, ELISA demonstrated a significant increase in the baseline ICAM-1 cell surface expression on the HDMEC. However, no induction of either E-selectin or VCAM-1 was noted. UVB also significantly augmented ICAM-1 induction by IL-1alpha and TNF-alpha. VCAM-1 was induced by stimulating HDMEC with IL-1alpha following a UVB irradiation dose of 100 mJ/cm2. Flow cytometric analysis of the HDMEC stimulated with IL-1alpha for 24h demonstrated that 12% of the cells expressed VCAM-1 but either IL-1alpha or UVB irradiation alone failed to induce VCAM-1 expression. Enhancement of T cell-HDMEC binding by IL-1alpha or TNF-alpha treatment was not significantly affected after UVB irradiation. This study demonstrated that UVB irradiation can alter ICAM-1 and VCAM-1 expression on the HDMEC surface and that augmentation of ICAM-1 expression and the IL-1alpha-dependent induction of VCAM-1 following UVB exposure might be important steps in the pathogenesis of sunburn.     

Primary papillary carcinoma arising in a thyroglossal duct cyst

We report a case of papillary carcinoma arising in a thyroglossal duct cyst, presenting with an anterior neck mass of a 31-year-old woman. The tumor was judged to be a primary lesion on the basis of intraoperative examination of the thyroid and pathologic findings of the mass. One year later, a small nodular mass in the left thyroid gland and lymph node enlargement of the right cervical lymph node were noted by follow-up imaging studies. Total thyroidectomy, right modified radical neck dissection and central neck dissection were performed. The thyroid gland revealed nodular hyperplasia without evidence of malignancy. On the other hand, the dissected neck lymph nodes revealed metastatic papillary carcinoma. Taken together, these findings suggested the tumor was a primary papillary carcinoma arising in the thyroglossal duct cyst.     

Altered expression of G1 regulatory proteins in human soft tissue sarcomas

CONTEXT: Soft tissue sarcomas constitute a heterogeneous group of tumors for which tumorigenesis is not fully understood. Altered cell-cycle regulation may underlie the development and/or progression of human malignancies. However, data concerning the occurrence of cell-cycle aberrations in soft tissue sarcomas are very limited. OBJECTIVES: To detect the abnormal features of cell-cycle regulatory proteins in soft tissue sarcomas and to determine the potential role of these proteins in clinical behavior. DESIGN: The p53 and Rb-cyclin D pathways were investigated by immunohistochemical studies of p53, mdm2, pRb, p16, cyclin D1, and cdk4 proteins, respectively. RESULTS: Of the 67 sarcomas analyzed, nuclear accumulation of p53 was detected in 25 samples (37%), and overexpression of mdm2 was found in 16 samples (24%). Both p53 and mdm2 expression correlated with tumor grade. Abnormalities involving the Rb-cyclin D pathway were identified in all of the tumors by the altered expression of either pRb (72%) or p16 (94%). Fourteen (21%) and 64 (96%) cases demonstrated cyclin D1 or cdk4 expression, respectively. Overexpression of cyclin D1 showed an association with pRb and p53. There was no correlation between pRb, p16, cyclin D1, or cdk4 and tumor grade or relapse. CONCLUSION: Disturbance in the cell-cycle regulatory system involving the p53 pathway and the Rb-cyclin D pathway is relatively frequent in soft tissue sarcomas and may be a contributing factor in the tumorigenesis of these tumors. The alterations in the Rb-cyclin D pathway probably constitute an early event, whereas the abnormalities in the p53 pathway seem to be involved in tumor progression. It is noteworthy that cyclin D1 may play a key role in linking both pathways.     

Surveillance of COVID-19–Associated Multisystem Inflammatory Syndrome in Children,South Korea

A concerning development during the coronavirus disease pandemic has been multisystem inflammatory syndrome in children. Reports of this condition in East Asia have been limited. In South Korea, 3 cases were reported to the national surveillance system for multisystem inflammatory syndrome in children. All case-patients were hospitalized and survived with no major disease sequelae.     

Direct versus indirect transfer for traumatic brain injury to James Cook University Hospital: a retrospective study

IntroductionPatients with traumatic brain injury are referred to the neurosurgical unit at James Cook University Hospital, Middlesbrough, either from local accident and emergency departments (direct transfer from the scene) or from other hospitals (indirect transfer). This study looked at the outcome in both groups.Material and methodsThis was a retrospective observational study using trauma audit research network data for patients treated for traumatic brain injury at the neurosurgery department at the neurosurgical unit at James Cook University Hospital.ResultsA total of 356 patients with traumatic brain injury were admitted under the care of neurosurgeons; 143 (40%) of these patients had a neurosurgical procedure. Of the patients undergoing a neurological procedure, 111 patients were transferred directly while 32 were indirect transfers; 213 patients were managed conservatively. Of those managed conservatively, 165 were transferred directly while 48 were indirect transfers.We compared the length of hospital stay and Glasgow Outcome Scale score for the patients based on whether they were conservatively managed or required surgery in the direct and indirect transfer groups. The difference in the length of stay in the surgical and conservative groups following direct and indirect transfer was insignificant (p = 0.07). The time to the operation in direct and indirect transfer was also not statistically significant (p = 0.06).ConclusionPatients are as safe, if not safer, by reaching the nearest trauma unit with facilities for resuscitation and imaging.     

Computed Tomography Evaluation of Forearm and Hand Muscles in Patients With Distal Radius Fracture

Introduction: Computed tomography (CT) can be used to assess bone status with measurement of Hounsfield unit (HU). The objective of this study was to evaluate whether HU of muscle might be associated with parameters of bone and muscle status. Methods: We reviewed 71 women aged over 50 yr of age who had distal radius fracture and underwent CT evaluation of affected wrist. We assessed HUs of forearm flexor muscles (flexor digitorum superficialis) and thenar muscles and bone HUs at the capitate and the ulnar head. Other parameters included femur neck and lumbar bone mineral density (BMD), upper extremity lean mass, hand grip strength, and muscle fiber cross-sectional area. We performed correlation analyses to determine associations between variables. Results: Thenar and forearm muscle HUs were significantly correlated with each other, but not with other parameters. HUs of the capitate and ulnar head were positively correlated with femur neck and lumbar BMDs and inversely correlated with age. Ulnar head HU was positively correlated hand grip strength. Conclusions: HUs of forearm and thenar muscles did not show significant correlations with bone or muscle parameters, although bone HUs correlated well with bone mineral densities. These results support the opportunistic use of CT for evaluating bone fragility. Clinical usefulness of muscle HU measurement needs further studies.     

Enhanced neurogenesis after transient global ischemia in the dentate gyrus of the rat

The dentate gyrus is one of the few areas of the mammalian brain where new neurons are continuously produced in adulthood. Certain insults such as epileptic seizures and ischemia are known to enhance the rate of neuronal production. We analyzed this phenomenon using the temporary occlusion of the two carotid arteries combined with arterial hypotension as a method to induce ischemia in rats. We measured the rate of cell production and their state of differentiation with a mitotic indicator, bromodeoxyuridine (BrdU), in combination with the immunohistochemical detection of neuronal markers. One week after the ischemic episode, the cell production in dentate gyrus was increased two- to threefold more than the basal level seen in control animals. Two weeks after ischemia, over 60% of these cells became young neurons as determined by colabeling with BrdU and a cytoplasmic protein (CRMP-4) involved in axonal guidance during development. Five weeks after the ischemia, over 60% of new neurons expressed calbindin, a calcium-binding protein normally expressed in mature granule neurons. In addition to more cells being generated, a greater proportion of all new cells remained in the differentiated but not fully mature state during the 2- to 5-week period after ischemia. The maturation rate of neurons as determined by the calbindin labeling and by the rate of migration from a proliferative zone into the granule cell layer was not changed when examined 5 weeks after ischemia. The results support the hypothesis that survival of dentate gyrus after ischemia is linked with enhanced neurogenesis. Additional physiological stimulation after ischemia may be exploited to stimulate maturation of new neurons and to offer new therapeutic strategies for promoting recovery of neuronal circuitry in the injured brain.