Clinical impact of amyloid PET using 18F-florbetapir in patients with cognitive impairment and suspected Alzheimer’s disease: a multicenter study

Annals of Nuclear Medicine - Amyloid positron emission tomography (PET) can reliably detect senile plaques and fluorinated ligands are approved for clinical use. However, the clinical impact of...     

Glycolysis inhibitors as a potential therapeutic option to treat aggressive neuroblastoma expressing GLUT1

Background/PurposeIncreased glycolysis is among the biochemical characteristics of cancerous tissue. The glucose transporter isoform 1 (GLUT1) gene encodes a key factor for glucose transport into cancerous tissue. However, the expression and functional significance of GLUT1 in neuroblastoma have not been fully characterized. Therefore, we investigated the association of GLUT1 expression with clinical outcomes in patients with neuroblastoma using immunohistochemical staining for GLUT1 in neuroblastoma tissues. We also assessed the efficacy of glycolysis inhibition as an anticancer treatment in neuroblastoma cell lines with altered expression of GLUT1.MethodsWe obtained total RNA from cancerous tissue by microdissection in 47 patients with neuroblastoma. GLUT1 expression levels were evaluated by quantitative real-time polymerase chain reaction. We analyzed the association of GLUT1 expression levels with clinical outcomes. We also examined changes in GLUT1 expression and proliferative responses in vitro using 4 neuroblastoma cell lines treated with a glycolysis inhibitor, 3-Bromopyruvate acid.ResultsElevated GLUT1 expression was associated with poor prognosis. Moreover, elevated GLUT1 expression independently predicted overall survival. Immunohistochemical analysis showed that GLUT1 expression tended to be localized to the centers of neuroblastoma cell nests. Our in vitro studies showed that 3-Bromopyruvate acid significantly suppressed the proliferation of neuroblastoma cells with high GLUT1 gene expression compared with those with low expression.ConclusionGlycolysis inhibitors are a potential therapeutic option for treating aggressive tumors expressing GLUT1.     

New epitope peptides derived from parathyroid hormone-related protein which have the capacity to induce prostate cancer-reactive cytotoxic T lymphocytes in HLA-A2+ prostate cancer patients

BACKGROUND: Parathyroid hormone-related protein (PTHrP) is produced by cancer cells and has been suggested to be responsible for malignancy-associated hypercalcemia and osteolysis after bone metatsases. Therefore, PTHrP is a promising target in the treatment of metastatic prostate cancer. METHODS: Seven PTHrP-derived peptides were prepared based on the HLA-A2 binding motif. These peptide candidates were screened by their ability to induce peptide-specific cytotoxic T lymphocytes (CTLs), and their ability to be recognized by immunoglobulin G (IgG). RESULTS: Both the PTHrP59-67 and PTHrP42-51 peptides were found to efficiently induce peptide-specific CTLs from peripheral blood mononuclear cells of HLA-A2+ prostate cancer patients with several HLA-A2 subtypes. These CTLs showed HLA-A2-restricted cytotoxicity toward prostate cancer cells. IgG reactive to the PTHrP42-51 peptide was frequently detected in prostate cancer patients. CONCLUSIONS: These results indicate that these two new PTHrP peptides will be useful in the peptide-based immunotherapy of HLA-A2+ prostate cancer patients, especially those with bone metastases.     

Border between N1 and N2 stations in lung carcinoma: lessons from lymph node metastatic patterns of lower lobe tumors

OBJECTIVE: Distinction of lymph node stations is one of the most crucial topics still not entirely resolved by many lung cancer surgeons. The nodes around the junction of the hilum and mediastinum are key points at issue. We examined the spread pattern of lymph node metastases, investigated the prognosis according to the level of the involved nodes, and conclusively analyzed the border between N1 and N2 stations. METHODS: We reviewed the records of 604 consecutive patients who underwent complete resection for non-small cell lung carcinoma of the lower lobe. RESULTS: There were 390 patients (64.6%) with N0 disease, 127 (21.0%) with N1, and 87 (14.4%) with N2. Whereas 11.3% of patients with right N2 disease had skip metastases limited to the subcarinal nodes, 32.6% of patients with left N2 disease had skip metastases, of which 64.2% had involvement of N2 station nodes, except the subcarinal ones. The overall 5-year survivals of patients with N0, N1, and N2 disease were 71.0%, 50.8%, and 16.7%, respectively (N0 vs N1 P = .0001, N1 vs N2, P < .0001). Although there were no significant differences in survival according to the side of the tumor among patients with N0 or N1 disease, patients with a left N2 tumor had a worse prognosis than those with a right N2 tumor (P = .0387). The overall 5-year survivals of patients with N0, intralobar N1, hilar N1, lower mediastinal N2, and upper mediastinal N2 disease were 71.0%, 60.1%, 38.8%, 24.8%, and 0%, respectively. Significant differences were observed between intralobar N1 and hilar N1 disease ( P = .0489), hilar N1 and lower mediastinal N2 disease (P = .0158), and lower and upper mediastinal N2 disease (P = .0446). Also, the 5-year survivals of patients with involvement up to station 11, up to station 10, and up to station 7 were 41.4%, 37.9% and 37.7%, respectively (difference not significant). CONCLUSIONS: N1 and N2 diseases appeared as a combination of subgroups: intralobar N1 disease, hilar N1 disease, lower mediastinal N2 disease, and upper mediastinal N2 disease. Interestingly, the survivals of patients with involvement up to interlobar nodes (station 11), main bronchus nodes (station 10), and subcarinal nodes (station 7) were identical. These data constitute the basis for a larger investigation to develop a lymph node map in lung cancer.     

L-carnitine could not improve hepatic warm ischemia-reperfusion injury despite ameliorated blood flow

BACKGROUND: Carnitine is applied to ameliorate ischemia-reperfusion (I/R) injury of several organs. However, application to hepatic I/R injury is not frequently reported. The aim of this study was to elucidate the effect of exogenous carnitine administration to ameliorate the warm hepatic I/R injury. MATERIALS AND METHODS: Male Wistar rats were divided into two groups, a carnitine group (Car);100 mg/kg of l-carnitine administration and a control group (C); vehicle administration. Thirty minutes after administration, the left hepatic lobes were given 60-min ischemia and then reperfused. Plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamate dehydrogenase (GLDH), tumor necrosis factor (TNF)-alpha, and lipoperoxides (LPO) were measured. Hepatic adenosine triphosphate (ATP) concentration was also measured. The hepatic blood flow was estimated using a Laser Doppler. The presence of apoptosis in the livers was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. RESULTS: In group Car, the blood flow of the left hepatic lobes was better recovered during the reperfusion period than in group C (P < 0.0001). Plasma levels of ALT, AST, GLDH, and TNF-alpha at 1 h after reperfusion were not significantly different between the groups. Although there were no statistical significances, ALT, AST, and TNF-alpha levels in group Car at 24 h after reperfusion tended to be higher than in group C. Plasma LPO levels were not different between the two groups. Also hepatic ATP concentration was not different between the two groups. TUNEL positive liver cells were visible only in group Car at 24 h after reperfusion, but not in the controls. CONCLUSIONS: Although carnitine administration improved the hepatic blood flow during the reperfusion period, we could not demonstrate a protective effect to the hepatic warm I/R injury.     

Homocysteine as a predictive factor for hip fracture in stroke patients

Risk of hip fractures in stroke patients is higher than that in a reference population. Hyperhomocysteinemia is regarded as a risk factor for ischemic stroke. The high prevalence of osteoporosis among patients with homocystinuria suggests that hyperhomocysteine may also increase the risk of fractures. To determine the association between homocysteine concentration and the risk of hip fractures, we studied a cohort of stroke patients with hemiplegia. Age-adjusted incidence rates of a hip fracture were calculated for quartiles of homocysteine concentrations. Cox proportional-hazard regression was used to calculate hazard ratios for quartiles of homocysteine levels. The initial enrolment of 433 hemiplegic patients with ischemic stroke, older than 65 years old, were followed for up to 10 years. The mean plasma homocysteine concentration at the enrolment was 14.1 +/- 5.2 micromol/L. There were 33 hip fractures among men and 46 among women during the mean follow-up period of 9.0 years. The age-adjusted incidence rates per 1000 person-years for hip fractures increased almost linearly from 2.89 in the lowest to 27.87 in the highest quartiles of homocysteine levels. We conclude that hyperhomocysteinemia is one of the risk factors for hip fractures in stroke patients.     

Traumatic dislocation of the hamate and pisiform: a case report and review of the literature

Isolated dislocation of the hamate bone and pisiform bone is rare. We describe the simultaneous complete dislocation of both the hamate and pisiform bones in a 27-year-old man who crushed his right hand in a rolling press. An open reduction and internal fixation with Kirschner wires was performed. Four weeks later, the Kirschner wires were removed and rehabilitation was started. At 6 months follow-up, the patient had minimal pain and full range of motion in the affected wrist joint and fingers. However, grip strength was 50% compared to his unaffected left hand, and sensation of the ulnar nerve area was reduced to almost 30% of that of his left hand. It appears that the ulnar nerve injury was the largest contributing factor to the poor outcome of our patient. Evaluation of soft-tissue injuries, especially nerve injury, is important in the treatment of complex carpal dislocations.     

Allograft glomerulitis: histologic characteristics to detect chronic humoral rejection

The aim of this study was to clarify the histopathologic significance of allograft glomerulitis in chronic allograft nephropathy (CAN). Review of our renal allograft biopsy files revealed 140 specimens with CAN among 115 selected patients. They were classified into two groups: one had CAN with glomerulitis (group G), and the other was free of this finding (group NG). We evaluated the clinicopathologic parameters as follows: levels of serum creatinine and proteinuria in the biopsy; presence of circulating anti-donor antibodies; allograft failure rate; history of biopsy-proven acute cellular rejection (ACR) and acute humoral rejection (AHR); complications of ACR and chronic rejection (CR); and results of immunofluorescence studies for C4d and HLA-DR. The glomerulitis group showed a significantly greater incidence of CR complications, the presence of circulating anti-donor antibodies, and C4d deposition in peritubular and glomerular capillaries. This group also showed higher levels of serum creatinine and proteinuria, higher graft loss rate, and increased AHR incidence, although the differences were not significant. There was also no statistical significance in the HLA-DR expression on tubular epithelial cells. The present results strongly suggest that humoral factors may play an important role in the progression of glomerulitis in CAN. Therefore, we suspect that glomerulitis in CAN is one of the main histologic markers for CR. The presence of glomerulitis may represent humoral factor-dependent inflammation. It should be considered an important diagnostic criterion for CR in addition to double-contour formation and elastica disruptions with or without subendothelial inflammation (Banff '97).     

Two-level posterior lumbar interbody fusion for degenerative disc disease: improved clinical outcome with restoration of lumbar lordosis

BACKGROUND CONTEXT: Although posterior lumbar interbody fusion (PLIF) for degenerative lumbar diseases is routine, there are few reports on double-level PLIF. PURPOSE: To evaluate the clinical outcomes of double-level PLIF. STUDY DESIGN/SETTING: A retrospective study of operated cases in Gifu, Japan. PATIENT SAMPLE: Nineteen patients (8 men and 11 women, 59.5+/-10.2 years) who underwent double-level PLIF between 1996 and 2001. OUTCOME MEASURES: Operation time, blood loss, complications, the Japanese Orthopaedic Association (JOA) score for back pain and lumbar sagittal alignment were evaluated. METHODS: Patients were examined retrospectively at follow-ups of 3.6+/-1.7 years. Primary diseases were spondylolisthesis, spinal canal stenosis, degenerative scoliosis and herniated intervertebral disc. Fusion areas were L3 to L5 in 15 cases and L4 to S1 in 4 cases. RESULTS: The mean JOA score increased from an initial score of 12.9+/-3.5 to 21.3+/-4.9 at the final follow-up. There was a positive correlation (R=0.718, p<.001) between the increase in lordotic angle and the increase in the JOA score. Several parameters suggested that the surgical invasiveness was not minimal. CONCLUSION: Double-level PLIF provided satisfactory results and preserved lumbar spine lordosis.     

Relationship between skeletal uptake of99mTc-HMDP and bone mineral density in elderly women

The relationship between bone mineral density in elderly women and the pattern of skeletal uptake of^99mTc-HMDP, especially in regard to skull uptake, was investigated. The whole-body skeletal uptake (WBSU) and whole-body skeletal tracer distribution patterns were studied in 86 disease-free women on bone scintigraphy with^99mTc-hydroxy-methylene-diphosphonate (HMDP). Bone scans were quantified by setting regions of interest (ROI) and bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry in all patients. WBSU and the skeletal distribution pattern were compared with bone mineral densities of the entire skeleton as well as selected regions. WBSU was high in the elderly and negatively correlated with regional bone mineral densities (r = ?0.403 to ?0.534). Among the regions, uptake by the skull increased with age more than in other regions in women and had the highest negative correlation with the bone mineral density. The skull uptake correlated negatively with total body BMD (r = ?0.583) and with lumbar BMD (r = ?0.561, p< 0.0001). Our results show that increased radionuclide uptake in bone scintigraphy, especially skull uptake was associated with decreased bone mineral density in elderly women, so that, increased skull uptake in elderly women would be a scintigraphic sign of post-menopausal or senile osteopenia.