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The purpose of this study was to determine the changing pattern of Salmonella serotypes causing acute diarrhoea in humans in Gwangju area, Korea, during 2000-2009. A total of 596 Salmonella isolated from culture of 29 896 faecal samples of patients with acute diarrhoea were included in this study. Faecal samples were collected from local hospitals and clinics in Gwangju area during January 2000-December 2009. The mean annual frequency of isolates for the 10 years was 2.0% (range, 0.9-6.0). The isolates were serologically classified into 43 different serotypes. The 10 most common serotypes were Salmonella Enteritidis (47.9%), S. Typhimurium (20.4%), S. Braenderup (3.2%), S. Montevideo (2.9%), S. Paratyphi B (2.9%), S. London (2.3%), S. Bardo (1.7%), S. Virchow (1.7%), S. Infantis (1.5%) and S. Typhi (1.5%), accounting for 86% of all the isolates. Temporal variations were observed in the distribution of different Salmonella serotypes over the years, and only S. Enteritidis and S. Typhimurium were persistent throughout the study period. Although age specificity varied with serotypes, Salmonella was isolated most frequently from children below 5 years of age (179/596, 30.0%). A seasonal trend was apparent, and the highest rates were found in the summer months. This is the first report of the annual frequency of isolation of Salmonella serotypes, and seasonal and age-specific patterns of salmonellosis in humans in Gwangju area, Korea, over a decade-long period. [ABSTRACT FROM AUTHOR]

Background: In men with prostate cancer, the gland usually contains two or more widely separate tumors. A critical issue of prostatic carcinogenesis is whether these multiple tumors are independent in origin. Molecular analysis of microsatellite (i.e., highly repeated, short nucleotide sequences) alterations in the DNA from separate tumors in the same prostate can be used to determine whether or not these separate tumors arise independently.Methods: Four microsatellite polymorphic markers (D8S133, D8S136, and D8S137, for a putative tumor suppressor gene on chromosome 8p, and D17S855, for the BRCA1 gene on chromosome 17q) were used to examine the pattern of allelic loss in prostate cancer from 19 patients who had two or more distantly separate tumors (i.e., located on contralateral sides or separated by at least half the anterior-posterior diameter of the prostate). Forty distantly separate tumors were microdissected, DNA samples were prepared from formalin-fixed, paraffin-embedded wholemount prostate tissue section, and the overall frequencies of loss of heterozygosity at the four loci were determined.Results: The pattern of allelic loss was compatible with independent tumor origin in 15 of 18 informative cases. A random discordant pattern of allelic deletion was observed in distantly separate tumors, whereas the same allele was consistently lost in cells from different regions of the same tumor. For three patients, the results were compatible with either intraglandular dissemination or independent origin of prostate cancer.Conclusions: Our data suggest that multiple tumors in some patients with prostate cancer have independent origin. [ABSTRACT FROM AUTHOR]

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with endometrial cancer was published in 2022. It was therefore decided, by both the ESMO and the Indian Society of Medical and Paediatric Oncology (ISMPO), to convene a virtual meeting in July 2022 to adapt the ESMO 2022 guidelines to take into account the variations in the management of endometrial cancer in Asia. These guidelines represent the consensus opinion of a panel of Asian experts representing the oncological societies of China (CSCO), India (ISMPO), Indonesia (ISHMO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO). Voting was based on scientific evidence and was conducted independently of the current treatment practices and treatment access constraints in the different Asian countries, which were discussed when appropriate. The aim of this guideline manuscript is to provide guidance for the optimisation and harmonisation of the management of patients with endometrial cancer across the different regions of Asia, drawing on the evidence provided by Western and Asian trials whilst respecting the variations in clinical presentation, diagnostic practices including molecular profiling and disparities in access to therapeutic options, including drug approvals and reimbursement strategies., Competing Interests: Funding All costs relating to this consensus conference were covered by the ESMO and the ISMPO from central dedicated funds. There was no external funding of the event or the manuscript production., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To evaluate the association between knee osteoarthritis (OA) and body composition parameters, and to analyze the correlations of both obesity and lower extremity muscle mass with radiographic knee OA in relation to sex., Methods: This was a cross-sectional study using data on body composition parameters measured using dual energy X-ray absorptiometry in 4246 participants in the Fifth Korea National Health and Nutrition Examination Survey. The relationships between knee OA and body composition parameters were evaluated. The associations between knee OA and the four subgroups corresponding to obesity and muscle mass percentage in both lower extremities were analyzed separately for each sex., Results: The lower extremity muscle mass showed a decreasing trend, while fat parameters showed an increasing linear trend (P for trend <0.05) with increasing severity of knee OA in women. The odds ratio of each quarter percentile group (25 percentile) for fat parameters showed an increasing trend, while that of the lower extremity muscle mass showed a decreasing linear trend in relation to knee OA in women (P for trend < 0.05). In women, low percentage of lower extremity muscle mass was more associated with knee OA regardless of obesity (P < 0.05). However, there were no associations between all body composition parameters and knee OA in men., Conclusion: In women, high fat mass and low lower extremity muscle mass were associated with presence and severity of knee OA. Lower extremity muscle mass was more closely correlated with knee OA than obesity in women., (Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Purpose: To assess the remodelling process of the bone graft and fused bodies after non-instrumented anterior interbody fusion with autogenous iliac graft in patients with spondylosis, infections, fractures, or disorders of the cervical spine., Methods: 68 patients aged 18 to 58 years who underwent non-plated anterior lower cervical interbody fusion with an iliac graft were retrospectively studied. Diagnoses of the patients were degenerative disc diseases (n=32), disc herniation (n=15), fractures (n=13), and tuberculosis (n=8). The Robinson and Smith technique was used to treat degenerative disc diseases and protruded disc, and the Bailey and Badgley procedure for fractures or tuberculosis of the cervical spine. 34, 25, and 9 patients underwent one-, 2-, and 3-segment fusions, respectively. 18 of the 25 patients underwent two-segment fusion with a single large bone block, and 7 with 2 separate bone blocks for each segment. Four of the 9 patients underwent three-segment fusion with a single large bone block, and 5 used separate grafts for each segment independently. Plain and stress radiography was primarily used to assess the fusion. Computed tomography and magnetic resonance imaging were also used in some patients. Some anterior graft extrusion (amounting to less than 10% of corresponding anteroposterior body width) was used to observe the remodelling during graft-take and thereafter. Postoperative cervical traction for 2 to 4 weeks, then cervical collar immobilisation for 4 to 12 weeks were strictly followed according to the numbers of fused segments. A halo vest was applied in 4 patients with fracture undergoing 3-segment fusion as they could not tolerate the prolonged bed rest or rigid cervical brace., Results: The mean time for the graft to fuse was 8.6 (range, 7-14) weeks in patients who underwent each segment fusion with independent free grafts, and 10 and 14 weeks in those who underwent 2- and 3-segment single large graft fusion, respectively. The final loss of disc height and joint angle were negligible, regardless of the extent of fusion. Bony absorption of the anteriorly protruded part of the graft began at postoperative week 10 (range, 6-28), which coincided with the time of graft-take and initiation of remodelling., Conclusion: The earliest sign of bony absorption of the anteriorly protruded part of the graft indicated the initiation of the graft-take and the graft remodelling. The inwaisting sign of the surgically fused block of vertebral bodies was a morphological adaptation. Despite the altered biomechanics of the spine in the fused area, the inwaisting sign indicated maintenance of normal function at the parafusion motion segments.

Objective: To evaluate the effectiveness of 2 different types of Cotrel-Dubousset instrument systems in stabilising thoracolumbar and lumbar spine fractures., Methods: Between January 1989 and December 1993, 45 fractures in 42 patients with unstable fracture or fracture dislocation of the thoracolumbar and lumbar spines were randomly assigned to 2 surgical treatments with Cotrel-Dubousset instrumentation-using either a long segment (Group 1) or a short segment (Group 2)-and short posterolateral fusion., Results: Consolidation of the fractured vertebral body and posterolateral fusion were achieved at a mean time of 4.5 months; fusion rates were 75% in Group 1 and 83% in Group 2. The average collapses of anterior vertebral body height in Group 1, in the immediate postoperative period and at the final follow-up, were 15% and 17%, respectively; and in Group 2, the figures were 16% and 24%, respectively. The correction of vertebral height and kyphosis at the last follow-up were lost more in Group 2 (5.7 degrees ) than in Group 1 (4.4 degrees ). There were neurological recoveries in 6 of the 9 cases of incomplete paraplegics, including complete recovery in 5, and one-Frankel grade increase in one. There were 15 instrument failures in 12 patients, including screw breakage in 3 Group 1 cases and 6 Group 2 cases. The plug dislodged in 3 Group 1 cases, and the hook dislodged in 3 Group 2 cases. In other words, instrument failures were more common in Group 2., Conclusion: Cotrel-Dubousset stabilisation of the fractured spine achieves fracture consolidation, but does not maintain the restored height and sagittal curve completely until fusion. The long rod and short fusion construct was more effective for all fracture types than was the short rod and fusion construct, although it leads to wider immobilisation of normal segments.

Purpose: To assess the effectiveness of Brooks' posterior stabilisation and fusion for the unstable atlantoaxial joint due to congenital dysplastic dens and trauma., Methods: We retrospectively studied records of 54 patients (36 males and 18 females; age range, 3-58 years) who underwent Brooks' posterior stabilisation procedure between March 1975 and December 1999, at the Catholic University of Korea Medical Center and Dong-Shin General Hospital, Seoul. A single-stranded Kirschner wire was used to stabilise the first 19 cases (thin wires in 12 cases and thick wires in 7), and double-stranded wires were used in the next 35 cases (thin wires in 4 cases and thick wires in 31). After surgery, patients were immobilised in bed with light Halter traction of the head, followed by cervical bracing., Results: Fusion was observed by X-ray postoperatively at 15 weeks in 48 patients. Reduction was achieved in 3 luxation cases (including the single case of rotatory fixation). Brooks' fusion failed in 4 patients with dens fractures and 2 with dens anomaly. Four dens fractures in cases of successful Brooks' fusion in Brooks' fusion did not unite. Wire failure occurred in 4 cases of thin single-stranded wire fixation, namely, 2 cases of dens fractures and 2 of dens anomaly., Conclusion: Brooks' procedure is safe and has a high fusion rate when double-stranded strong wire fixation of the atlantoaxial joint is combined with meticulous bone grafting and subsequent cervical bracing.

Fourty-two patients (34 males and 8 female) with traumatic spondylolisthesis of the axis were studied in a retrospective review There were 20 stable and 22 unstable fractures. The 22 unstable fractures were treated surgically: 16 anterior interbody fusion (10 non-plated and 6 plated), 4 pedicle screw fixation for osteosynthesis of the fractured pedicles, and 2 posterior wire fixation for flexion and axial load injury. For all non-surgical cases, head halter tractions for 1 to 8 weeks was prescribed and a cervical orthosis was worn for an additional 6 to 18 weeks. The surgical cases underwent 5 to 7 days of preoperative and 1 to 4 weeks of post-operative head halter traction. In all cases pedicle fractures united after 13 weeks on average in group treated conservatively, 12 weeks (11 to 13 weeks) in the posterior wiring group, 8 weeks (7 to 9 weeks) in the group in which pedicle screws were used, and 11 weeks (9 to 15 weeks) in the anterior fusion group (13 weeks in non-plated, and 8 weeks in plated). There were no differences in patterns of anterior fusion between those in the non-plated and plated groups. There were no non-unions of fractured pedicles and there was no late instability of the C2-C3 or neurological complications. In 2 cases in the posterior surgery group, there was mild nuchal discomfort and some rigidity for a short while postoperatively. Final outcomes were good in all cases.

Multiple mechanisms, such as gene mutations, amplifications, and rearrangements, as well as perturbed mitogen and receptor function, are likely to contribute to glioma formation. The MET (also known as c-met proto-oncogene located at 7q31-34 has been shown to be amplified in human gliomas, and activating mutations within the tyrosine kinase domain of MET have been causally related to tumorigenesis in hereditary papillary renal cell carcinoma. To elucidate the role of MET gene in glioma formation, sporadic gliomas from 11 patients were examined for MET gene mutations and allelic duplications or deletions by polymerase chain reaction-single strand conformational polymorphism analysis and fluorescence in situ hybridization. Three of 11 sporadic gliomas showed a deletion of one copy of the MET gene, and a specific METgene missense mutation in the remaining gene copy was detected in one of those tumors. The corresponding sequence in non-tumor DNA was normal in all cases. Three of 11 sporadic gliomas showed duplication of one copy of the MET gene, but none of them contained mutations. One tumor showed METamplification without mutation. Three showed neither allelic change nor mutation. These data suggest that somatic MET gene mutation may play a role in the development of a subgroup of sporadic gliomas. However, MET mutations appear to be absent in the majority of sporadic gliomas.

Multiple endocrine neoplasia type 1 (MEN1) is characterized by the development of endocrine tumors of the parathyroid and pituitary glands, pancreas, and duodenum. Less frequently occurring tumors associated with MEN1 include non-endocrine tumors such as lipomas and angiofibromas. An increased incidence of thyroid neoplasms, leiomyomas, adrenal cortical hyperplasia, hepatic focal nodular hyperplasia, and renal angiomyolipoma has been noted in the MEN1 population. The pathogenesis of non-neuroendocrine tumors in MEN1 is unknown. We report a complex clinical course and a detailed morphologic and genetic analysis of a series of tumors that developed in a patient with MEN1. All tumors were microdissected and analyzed for loss of heterozygosity of the MEN1 gene. A germline mutation of the MEN1 gene was detected, and deletions of the MEN1 gene were consistently detected in multiple neuroendocrine tumors involving the parathyroid glands and the pancreas and a hepatic neuroendocrine tumor metastasis, as predicted by Knudson's "two hit" hypothesis. Two hits of the MEN1 gene were also detected in esophageal leiomyoma tissue, suggesting that tumorigenesis was directly related to the patient's underlying MEN1. In contrast, follicular thyroid adenoma, papillary thyroid carcinoma, hepatic focal nodular hyperplasia, and adrenal cortical hyperplasia consistently showed retained heterozygosity of the MEN1 gene with flanking markers and an intragenic marker. Therefore, these tumors appear to develop along pathogenetic pathways that are different from classical MEN1-associated tumors.

Background: Medulloblastomas can occur sporadically or may be associated with hereditary tumor syndromes including familial adenomatous polyposis (FAP) and nevoid basal cell carcinoma syndrome (NBCCS)., Methods: The authors performed a retrospective analysis for allelic deletion of the adenomatous polyposis coli (APC) and PTCH gene loci using paraffin embedded medulloblastoma specimens from patients who were admitted to Children's National Medical Center in Washington, DC, between 1982 and 1997. Thirty-five cases from which tumor and normal tissue could be procured were analyzed. Two of the analyzed cases had a positive family and personal history for NBCCS; in both cases the histology of the medulloblastoma revealed a desmoplastic phenotype. Thirty-three cases were not known to be associated with hereditary disease; 2 of those cases revealed desmoplastic and 31 cases revealed nondesmoplastic "classic" medulloblastoma histology., Results: Although medulloblastoma tumorigenesis has been associated strongly with FAP associated with APC germline mutation, none of the 22 informative sporadic cases revealed loss of heterozygosity of the APC gene locus. PTCH gene deletion was detected in the tumors of both patients with NBCCS. In contrast, only 1 of 33 sporadic medulloblastomas revealed PTCH gene deletion. The sporadic case with PTCH gene deletion did not demonstrate the desmoplastic phenotype., Conclusions: In conjunction with previous studies, the data from the current study confirm that allelic deletion occurs in NBCCS-associated medulloblastomas, consistent with the role of PTCH as a tumor suppressor gene. However, in sporadic medulloblastomas, allelic deletion of PTCH is an infrequent event. Morphologic examination in conjunction with genetic analysis of PTCH gene deletion in medulloblastoma tissue may prove to be a quick and efficient test with which to screen for NBCCS in patients with medulloblastomas. Although medulloblastoma is a component of Turcot syndrome with demonstrated APC mutations, APC gene deletions appear to be absent or very uncommon in patients with sporadic and NBCCS-associated medulloblastomas.

Future improvements in the diagnosis and treatment of human gliomas might rely on obtaining more specific information concerning the biologic characteristics of individual tumor cells. Telomerase, a ribonucleoprotein that synthesizes telomeres, has been reported to be expressed in a majority of human tumors, including several subtypes of brain tumor. We hypothesized that a quantitative assay for telomerase activity, combined with selective microdissection of tumor or normal brain cells, might reveal telomerase gain-of-function to be important in the pathogenesis of gliomas and that telomerase levels might have prognostic significance. We used tissue microdissection for selective analysis of tumor cells obtained from eight patients with glioma, one with a meningioma, and one with a primary B-cell lymphoma of the central nervous system. Normal brain tissue microdissected from another patient was used as a control. Telomerase activity was screened by an electrophoretic method and then assayed by a quantitative ELISA method. All of the eight gliomas had positive telomerase activity, as did the lymphoma. The meningioma and normal brain were negative. Quantitative analysis of telomerase activity did not correlate with tumor grade nor predict outcome. Selective tissue microdissection, combined with qualitative and quantitative telomerase assays, permits rapid and reliable detection of telomerase activity in diverse brain tumor tissues. These preliminary findings suggest that telomerase reactivation is a frequent event in glioma tumorigenesis that can be sensitively and specifically detected in gliomas of all histologic grades. Furthermore, specific detection of telomerase reactivation represents another mechanism by which tumor formation and progression might become the target of novel therapeutics.

Despite extensive characterization of genetic changes in gliomas, the underlying etiology of these tumors remains largely unknown. Spontaneous DNA damage due to hydrolysis, methylation, and oxidation is a frequent event in the brain. Failure of DNA repair following this damage may contribute to tumorigenesis of gliomas. Uracil DNA glycosylase (UDG), an enzyme which excises uracil from DNA, is an important component of the base excision repair pathway. The sequence of a human homologue of uracil DNA glycosylase gene (UNG) has been recently identified. We performed PCR-based SSCP mutational analysis of UNG in 11 sporadic gliomas (six glioblastomas, two anaplastic astrocytomas, and three oligodendrogliomas) and eight glioblastoma cell lines. One out of six sporadic glioblastomas had a point mutation in exon 3, which resulted in a missense mutation in codon 143. None of the eight glioblastoma cell lines or the five non-glioblastoma sporadic gliomas showed a mutation. Genetic alterations of UNG may play a role in the development of a subset of primary glioblastomas.

The lectin, wheatgerm agglutinin (WGA) conjugated to horseradish peroxidase (HRP), previously was shown to be transported into the central nervous system following application by intranasal irrigation. The current study investigated the hypothesis that uptake of molecules, such as the lectin-conjugate, by olfactory receptor cells would mimic internalization of other substances including odorants. This process would result in both premature death of receptor cells and increased turnover of their precursors, globose basal cells. Tetramethylbenzidine histochemical analysis showed the presence of significant amounts of the lectin-conjugate in both the receptor epithelium and olfactory bulb until at least 2 weeks postintranasal application. Neither supporting nor globose basal cells contained WGA-HRP, suggesting that uptake was primarily into olfactory receptor cells. Cell turnover, assessed by tritiated-thymidine (thymidine) autoradiography, increased both 1 and 2 weeks, but not 3 and 4 weeks, following intranasal irrigation with WGA-HRP. Most of the cells containing thymidine labelling appeared to be globose basal cells, although supporting cells also occasionally exhibited labelling. Survival of either mature or immature receptor cells in the epithelium, indicated by epithelial thickness and cell density of the septal epithelium, also declined following treatment. These data suggest that uptake of substances may result in cell loss from the olfactory epithelium and increased mitotic activity of basal cells.