Overexpression of the aldo-keto reductase family protein AKR1B10 is highly correlated with smokers' non-small cell lung carcinomas.

PURPOSE: Squamous cell carcinoma (SCC) and adenocarcinoma of the lung are currently subject to similar treatment regimens despite distinct differences in histology and epidemiology. The aim of this study is to identify a molecular target with diagnostic and therapeutic values for SCC. EXPERIMENTAL DESIGN: Genes specifically up-regulated in SCC were explored through microarray analysis of 5 SCCs, 5 adenocarcinomas, 10 small cell lung carcinomas, 27 normal tissues, and 40 cancer cell lines. Clinical usefulness of these genes was subsequently examined mainly by immunohistochemical analysis. RESULTS: Seven genes, including aldo-keto reductase family 1, member B10 (AKR1B10), were identified as SCC-specific genes. AKR1B10 was further examined by immunohistochemical analysis of 101 non-small cell lung carcinomas (NSCLC) and its overexpression was observed in 27 of 32 (84.4%) SCCs and 19 of 65 (29.2%) adenocarcinomas. Multiple regression analysis showed that smoking was an independent variable responsible for AKR1B10 overexpression in NSCLCs (P < 0.01) and adenocarcinomas (P < 0.01). AKR1B10 staining was occasionally observed even in squamous metaplasia, a precancerous lesion of SCC. CONCLUSION: AKR1B10 was overexpressed in most cases with SCC, which is closely associated with smoking, and many adenocarcinoma cases of smokers. These results suggest that AKR1B10 is a potential diagnostic marker specific to smokers' NSCLCs and might be involved in tobacco-related carcinogenesis.     

Non-traumatic renal arteriopelvic fistula

PURPOSE: In the present paper, we report on a 34-year-old female with macroscopic hematuria due to a nontraumatic renal arteriopelvic fistula (APF). The patient initially presented at another hospital with asymptomatic macroscopic hematuria. Following abdominal ultrasonography, computed tomography (CT) and laboratory data, no abnormal findings were seen. Therefore, the patient was referred to Teine Keijinkai Hospital for a more precise evaluation of the urinary tract and vascular abnormality. METHODS/RESULTS: Endoscopically, there was bleeding from the right ureteral orifice, so the patient was admitted for further examination. No abnormal findings were seen on urinary cytology and following an intravenous pyelogram. A selective right lower polar renal arteriogram revealed arterial extravasation directly into the pelvis before the venous phase, so APF of the kidney was diagnosed. The patient had no history of urinary tract trauma, so the APF was thought to be idiopathic. After transcatheter arterial embolization (TAE) with a gelatine sponge, macroscopic and microscopic hematuria disappeared and a low-density area was seen in the middle pole of the right kidney in an abdominal CT scan 4 days after TAE. This was thought to be renal infarction due to TAE. CONCLUSIONS: After discharge, the patient had no further hematuria.     

Four novel mutations in the thiazide-sensitive Na-Cl co-transporter gene in Japanese patients with Gitelman's syndrome.

BACKGROUND: Gitelman's syndrome (GS) is an autosomal recessive disorder resulting from inactivating mutations in the thiazide-sensitive Na-Cl co-transporter (NCCT) gene. To date, almost 90 mutations have been identified. It is possible that there is a population-specific distribution of mutations. In this study, we analysed mutations in the NCCT gene of seven Japanese patients with GS. METHODS: Peripheral blood mononuclear cells were isolated from patients with GS, their family members and healthy control subjects. A mutation analysis of the NCCT gene was performed completely by direct automated sequencing of polymerase chain reaction-amplified DNA products. In patients with a deletion or splice site mutation, we undertook cDNA sequence analysis. RESULTS: We identified nine mutations. Five of them [c.185C>T (Thr60Met), c.1712C>T (Ala569Val), c.1930C>T (Arg642Cys), c.2552T>A (Leu849His) and c.1932delC] have been reported in Japanese patients, but not in GS patients from other ethnic groups. The remaining four mutations [c.7A>T (Met1Leu), c.1181_1186+20del26, c.1811_1812delAT and IVS16+1G>A] were novel. In cDNA derived from a patient with c.1181_1186+20del26, a deletion of exon 9 and a frameshift at the start of exon 10 were observed. In cDNA derived from patients with IVS16+1G>A, an additional 96 bp insertion between exons 16 and 17 was observed. Six out of seven patients were compound heterozygotes, and the remaining one carried a single heterozygous mutation. CONCLUSIONS: We found four novel mutations in the NCCT gene in seven Japanese patients with GS. Moreover, our study suggests that the distribution of mutations in the NCCT gene in Japanese GS patients potentially differs from that in other populations.     

Adjacent segment disease after anterior cervical interbody fusion

BACKGROUND CONTEXT: There have been many follow-up studies on anterior interbody fusion for cervical nerve root and spinal cord compression, and excellent neurological outcomes have been reported. However, postoperative degenerative changes at adjacent discs may lead to the development of new radiculopathy or myelopathy. In the previous reports, the incidence of symptomatic adjacent segment disease has ranged from 7% to 15%. PURPOSE: The present study was undertaken to investigate the incidence of symptomatic adjacent segment disease after anterior cervical interbody fusion (ACIF) and to identify the factors that are related to the development of this disease. STUDY DESIGN/SETTING: This is a retrospective cohort study. PATIENT SAMPLE: A total of 112 patients were followed up clinically and radiologically for more than 2 years. OUTCOME MEASURES: Follow-up evaluation was primarily by means of clinical visits. The postoperative course of any symptoms, the findings of neurological examination and serial follow-up radiographs were performed in all patients. METHODS: The diagnosis of symptomatic adjacent segment disease was based on the presence of new radiculopathy or myelopathy symptoms referable to an adjacent level, and the presence of a compressive lesion at an adjacent level by magnetic resonance imaging or myelography. We evaluated the correlation between the incidence of symptomatic adjacent segment disease and the following clinical parameters (age at operation, sex, number of the levels fused) and radiological parameters (preoperative cervical spine alignment, preoperative range of motion of C2-C7 cervical spine, anteroposterior spinal canal diameter, preoperative existence of an adjacent segment degeneration on plain radiograph, myelography and magnetic resonance imaging [MRI]). RESULTS: Symptomatic adjacent segment disease developed in 19 of 112 patients (19%) followed. A Kaplan-Meier survival analysis was performed in order to follow the disease-free survival of the entire series of patients. The disease-free survival rates were 89% at 5 years, 84% at 10 years and 67% at 17 years. The incidences of indentation of dura matter on preoperative myelography or disc protrusion on MRI at the adjacent level were significantly higher in disease cases (p=.0087, .0299, respectively; chi-squared test). However, the other parameters did not show a statistically significant difference. There were seven cases (37%) who had failure of nonoperative treatment and additional operations were performed. CONCLUSIONS: The incidence of symptomatic adjacent segment disease after ACIF was higher when preoperative myelography or MRI revealed asymptomatic disc degeneration at that level regardless of the number of the levels fused, preoperative alignment, spinal canal diameter or fusion alignment.     

Cross-sectional area of the posterior extensor muscles of the cervical spine in whiplash injury patients versus healthy volunteers--10 year follow-up MR study

IntroductionLong-term follow-up studies focusing on the posterior extensor muscles in patients suffering from whiplash injury are scarce. The purpose of this study was to elucidate the changes in the posterior extensor muscles 10 years after whiplash injury.MethodsTwenty-three patients who had suffered from whiplash injury in 1994–1996 and had undergone MRI using a 1.5-T superconductive imager participated in this follow-up study (13 males, 10 females, mean age 51.8 years, mean follow-up 11.5 years). In addition, 60 healthy volunteers who had undergone MRI in the same period were included as controls (36 males, 24 females, mean age 47.8 years, mean follow-up 11.1 years). All participants underwent follow-up MRI. The cross-sectional areas of the deep posterior muscles (CSA) including the multifidus, semispinalis cervicis, semispinalis capitis, and splenius capitis were digitally measured at C3-4, C4-5, and C5-6 using NIH image. The long-term changes in the CSA were compared between the two groups. In addition, correlations between the CSA and cervical spine-related symptoms were evaluated.ResultsThe mean total CSA per patient (the sum of the area from C3-4 to C5-6) was 4811.6 ± 878.4 mm² in the whiplash patients and 4494.9 ± 1032.7 mm² in the controls at the initial investigation (p = 0.20), and 5173.4 ± 946.1 mm² and 4713.0 ± 1065.3 mm² at the follow-up (p = 0.07). The mean change in CSA over time was 361.8 ± 804.9 mm² in the whiplash patients and 218.1 ± 520.7 mm² in the controls (p = 0.34). Ten whiplash patients (43.5%) had neck pain and 11 (47.8%) had shoulder stiffness. However, there was no difference in the change in CSA over time between the symptomatic and asymptomatic patients.ConclusionsThere was no significant difference in the change in CSA between whiplash patients and healthy volunteers after a 10-year follow-up period. In both groups, the cross-sectional area slightly increased at follow-up. In addition, there was no association between the change in CSA and clinical symptoms such as neck and shoulder pain. These results suggest that whiplash injury is not associated with symptomatic atrophy of the posterior cervical muscles over the long term.     

一氧化氮在静水压下对人体腰椎间盘蛋白多糖合成的影响

[目的]探讨一氧化氮对人体腰椎间盘组织蛋白多糖合成的影响及静水压对蛋白多糖合成调节过程中一氧化氮是否起到中间介质作用。[方法]72例后方腰椎间盘摘除术的志愿患者中获取新鲜的72个椎间盘样品被切成1～2mm^3细片后，与1ml培养基DMEM一同装入塑料注射器中，放入培养椎间盘组织的压力装置，蛋白多糖合成由^35S-硫酸盐结合率来测定。无活性、稳定的一氧化氮的最终产物亚硝酸盐浓度由分光光度法来测定。[结果]静水压在0．3MPa蛋白多糖合成最高，约为0．1MPa的1．3倍；3MPa抑制蛋白多糖合成率。但静水压对一氧化氮的产生起着逆转效应。在0．3MPa一氧化氮的产生量和0．1MPa的相比略微降低，而3MPa增加一氧化氮的产生量，约是0．1MPa的1．34倍。一氧化氮合成酶的竞争性抑制剂N^C-methyl-L-arginine（简称L-NMA，10-1000μmol）在0．3MPa诱导增加蛋白多糖合成率，而3MPa降低对蛋白多糖合成率的抑制作用。[结论]在人体腰椎间盘细胞静水压影响着一氧化氮生成，且一氧化氮对蛋白多糖合成率改变起着中间介质调节作用。     

一期前路病灶清除加植骨术治疗化脓性脊椎炎

抗生素效力的高度发展已使化脓性脊椎炎患者相对少见。然而,随着糖尿病、恶性肿瘤及滥用毒品等患者的增多,化脓性脊椎炎在这些患者中的发病日益增加[1,2]。传统的治疗包括卧床、支具外固定以及静脉应用抗生素;但上述治疗周期较长,且仍有相当一部分患者治疗无效,病变进行性发展,