Evaluation of a diagnostic 18F-FDG PET/CT strategy for differentiating benign from malignant retroperitoneal soft-tissue masses.

AIM: To investigate the optimal combined 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET)/computed tomography (CT) diagnostic criteria for distinguishing between benign and malignant retroperitoneal soft-tissue masses (RPMs). MATERIALS AND METHODS: A total of 74 patients (M:F=34:40; age, 53±13.2 years) who underwent FDG PET/CT for the initial work-up of RPMs were included. The maximum standardised uptake value (SUVmax), tumour size, presence of fat or calcifications and separated hypermetabolic lesions were included as PET/CT diagnostic parameters. Receiver-operating characteristic (ROC) curves were used to compare the diagnostic performance. RESULTS: The final pathological diagnoses included 52 malignant and 22 benign tumours. High SUVmax (>4.8) and large size (>13 cm) favoured malignancy, and yielded a diagnostic accuracy and AUC of 64.9%, 0.820±0.059, and 68.9%, 0.738±0.061, respectively. In a subgroup of RPMs with a fat component, both SUVmax and size were significantly different between benign and malignant RPM, which yielded a diagnostic accuracy and AUC of 91%, 0.977±0.024 (cut-off, 1.9 cm) and 87.9%, 0.865±0.072 (cut-off, 13 cm), respectively. In a subgroup without a fat component, only SUVmax was significantly different with an accuracy of 90.2% and AUC of 0.919±0.043. The optimal diagnostic flow by combining SUVmax and tumour size after dividing patients into two groups according to the presence of fat showed a sensitivity of 90.4%, a specificity of 95.5%, and an accuracy of 91.9%. CONCLUSIONS: The combination of SUVmax and size according to the presence of a fat component may be the optimal PET/CT diagnostic criteria for distinguishing benign and malignant RPMs.

Aloe vera for treating acute and chronic wounds.

BACKGROUND: Aloe vera is a cactus-like perennial succulent belonging to the Liliaceae Family that is commonly grown in tropical climates. Animal studies have suggested that Aloe vera may help accelerate the wound healing process. OBJECTIVES: To determine the effects of Aloe vera-derived products (for example dressings and topical gels) on the healing of acute wounds (for example lacerations, surgical incisions and burns) and chronic wounds (for example infected wounds, arterial and venous ulcers). SEARCH METHODS: We searched the Cochrane Wounds Group Specialised Register (9 September 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 3), Ovid MEDLINE (2005 to August Week 5 2011), Ovid MEDLINE (In-Process & Other Non-Indexed Citations 8 September 2011), Ovid EMBASE (2007 to 2010 Week 35), Ovid AMED (1985 to September 2011) and EBSCO CINAHL (1982 to 9 September 2011). We did not apply date or language restrictions. SELECTION CRITERIA: We included all randomised controlled trials that evaluated the effectiveness of Aloe vera, aloe-derived products and a combination of Aloe vera and other dressings as a treatment for acute or chronic wounds. There was no restriction in terms of source, date of publication or language. An objective measure of wound healing (either proportion of completely healed wounds or time to complete healing) was the primary endpoint. DATA COLLECTION AND ANALYSIS: Two review authors independently carried out trial selection, data extraction and risk of bias assessment, checked by a third review author. MAIN RESULTS: Seven trials were eligible for inclusion, comprising a total of 347 participants. Five trials in people with acute wounds evaluated the effects of Aloe vera on burns, haemorrhoidectomy patients and skin biopsies. Aloe vera mucilage did not increase burn healing compared with silver sulfadiazine (risk ratio (RR) 1.41, 95% confidence interval (CI) 0.70 to 2.85). A reduction in healing time with Aloe vera was noted after haemorrhoidectomy (RR 16.33 days, 95% CI 3.46 to 77.15) and there was no difference in the proportion of patients completely healed at follow up after skin biopsies. In people with chronic wounds, one trial found no statistically significant difference in pressure ulcer healing with Aloe vera (RR 0.10, 95% CI -1.59 to 1.79) and in a trial of surgical wounds healing by secondary intention Aloe vera significantly delayed healing (mean difference 30 days, 95% CI 7.59 to 52.41). Clinical heterogeneity precluded meta-analysis. The poor quality of the included trials indicates that the trial results must be viewed with extreme caution as they have a high risk of bias. AUTHORS' CONCLUSIONS: There is currently an absence of high quality clinical trial evidence to support the use of Aloe vera topical agents or Aloe vera dressings as treatments for acute and chronic wounds.

Characterization of congenital lymphatic and blood vascular malformations in the head and neck using blood pool scintigraphy and spect.

The purpose of this study was to investigate the usefulness and diagnostic efficacy of blood pool (BP) scintigraphy and SPECT for characterizing congenital vascular malformations (CVMs) in the head and neck area. A total of 154 patients suspected of having head and neck CVMs underwent whole-body BP scintigraphy and head and neck BP SPECT using 99mTc-labeled red blood cells. Based on SPECT findings, CVMs were classified into lymphatic malformation/ non-(blood) vascular disease (LM/NVD, no distinct uptake), arterio-venous malformation (AVM, abnormal uptake in lesions and asymmetrically increased jugular vein uptake on ipsilateral side), venous malformation (VM, strong uptake in lesions with symmetric jugular vein uptake), and veno-lymphatic malformation (VLM, no or mild uptake on lesions with symmetric jugular vein uptake). The sensitivities and specificities of BP SPECT for diagnosing each subtype of head and neck CVM were 100% (13/13) and 97.1% (137/141) for LM/NVD, 61.1% (22/36) and 99.1% (117/118)for AVM, 91.7% (88/96) and 79.3% (46/58) for VM, and 55.6% (5/9) and 93.7% (136/145) in VLM, respectively. The overall accuracy for characterizing CVMs by head and neck BP SPECT was 83.1% (128/154). In conclusion, BP SPECT is a useful method for classifying CVMs in the head and neck area due to its high diagnostic efficacy.

Characterization of congenital vascular malformation in the extremities using whole body blood pool scintigraphy and lymphscintigraphy.

The purpose of this study was to investigate the clinical usefulness of combined whole body blood pool scintigraphy (WBBPS) and lymphscintigraphy (LS) in the characterization of patients with congenital vascular malformations (CVMs) of the extremities. Subjects included 134 patients who underwent Tc-99m RBC WBBPS and Tc-99m filtered tin colloid (or antimony sulfur colloid) LS on initial diagnosis. Scintigraphic results were interpreted as arteriovenous malformations (AVMs), venolymphatic malformations (VLMs), lymphatic malformations (LMs), and venous malformations (VMs). Final diagnosis of the type of vascular malformation was determined by physical examination, magnetic resonance imaging (MRI), angiography, duplex ultrasonography, and/or biopsy results. The final diagnosis demonstrated that 14 of the study subjects had an AVM, 29 had a HLM, 20 had a LM, and 71 had a VM. The sensitivity of WBBPS and LS in the characterization of CVM was 85.7% (12/14) for AVMs, 96.6% (28/29) for VLMs, 95.0% (19/20) for LMs, and 88.7% (63/71) for VMs. The specificity was 100% for AVMs (120/120), 91.4% for VLMs (96/105), 99.1% for LMs (113/114), and 98.4% for VMs (62/63). The overall accuracy of WBBPS and LS was 91.0% (122/134). Our results show that combination of WBBPS with LS can characterize extremity CVMs in patients with high diagnostic accuracy, and may thus be useful for making optimal treatment decisions.

Profiling signalling pathways of the receptor activator of NF-kappaB ligand-induced osteoclast formation in mouse monocyte cells, RAW264.7.

Cell-based signal chemical genomics can profile the signalling pathway for certain cellular events by using a target-known chemical library. To ascertain its usefulness, the receptor activator of NF-kappaB ligand (RANKL)-induced osteoclastogenesis in mouse monocyte/macrophage cells RAW264.7 was used as an in vitro experimental model. Of 180 target-known inhibitors/activators formatted in a 384-well plate, 8 chemicals were shown to inhibit the osteoclast formation, but 4 chemicals enhanced this process. A variety of references support, or possibly lead one to expect the effects of these 12 chemicals on the cellular process of osteoclastogenesis in RAW264.7 cells, but several signalling pathways were newly found in this study; for example, CA-074 Me inhibiting cathepsin B and nitrendipine blocking the calcium channel could have the potential to inhibit the osteoclast formation as well as bone resorption. This is a simple but very fast and powerful method of profiling the signalling pathway of certain cellular events. Signal chemical genomics could provide invaluable information for the exploration of new target signalling processes and further target-based drug discovery strategies.

Lymphscintigraphy predicts response to complex physical therapy in patients with early stage extremity lymphedema.

We investigated whether baseline lymphscintigraphic findings can predict long-term response to complex physical therapy (CPT) in patients with early stage extremity lymphedema. Twenty patients with unilateral extremity lymphedema of clinical stage I or II underwent CPT after baseline lymphscintigraphy. Therapeutic responses (good vs. poor) were evaluated at 1 year post-CPT based on changes in skin status and subjective symptoms, and percent volume reductions and compared with clinical factors and lymphscintigraphic findings. Eleven patients showed good response to CPT with significant volume reduction of edematous extremities, and no significant volume reduction was observed in the remaining 9. Patients with good or poor responses to CPT showed no significant differences in terms of clinical variables. However, significant differences were observed between the lymphscintigraphic findings of these patients. More specifically, a lymphscintigraphic finding of main lymphatic vessels without collateral lymphatic vessels was the best predictor for a good response to CPT; the sensitivity, specificity and accuracy of this lymphscintigraphic finding is 91% (10/11), 100% (9/9) and 95% (19/20), respectively. In patients with unilateral extremity lymphedema of early stage, baseline lymphscintigraphy may usefully predict long-term response to CPT.

Early life stress experience may blunt hypothalamic leptin signalling.

The aim of this study was to investigate whether neonatal maternal separation (MS) - chronic stress experience in early life - affects the anorectic efficacy of leptin in the offspring at adolescence. Sprague-Dawley pups were separated from the dam daily for 3 h during postnatal day 1-14 or left undisturbed as non-handled controls (NH). NH and MS male pups received an intraperitoneal leptin (100 µg/kg) or saline on postnatal day (PND) 28, and then food intake and body weight gain were recorded. The hypothalamic levels of leptin-signalling-related genes, phosphorylated signal transducer and activator of transcription-3 (pSTAT3) and protein-tyrosine phosphatase 1B (PTP1B) were examined at 40 min after a single injection of leptin on PND 39 by immunohistochemistry and Western blot analysis. Leptin-induced suppressions in food intake and weight gain was observed in NH pups, but not in MS. Leptin increased pSTAT3 in the hypothalamic arcuate nucleus of NH pups, but not of MS. Interestingly, basal levels of the hypothalamic PTP1B and pSTAT3 were increased in MS pups compared with NH controls. The results suggest that neonatal MS experience may blunt the anorectic efficacy of leptin later in life, possibly in relation with increased expressions of PTP1B and/or pSTAT3 in the hypothalamus.

Prognostic significance of volume-based 18F-FDG PET/CT parameter in patients with surgically resected non-small cell lung cancer. Comparison with immunohistochemical biomarkers.

AIM: We investigated the prognostic value of volume-based 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) parameters compared with other factors including several immunohistochemical biomarkers in patients with surgically resected non-small cell lung cancer (NSCLC). STUDY PARTICIPANTS: 290 patients with surgically resected and histopathologically confirmed NSCLC. The maxmum standardized uptake value (SUVmax) and metabolic tumour volume (MTV) of the primary tumour were obtained on 18F-FDG PET/ computed tomography (CT) for initial staging and Ki-67 labeling index (LI), p16, CD31 and cyclin E were evaluated in the primary tumours by immunohistochemical staining. Survival analyses for variables including PET parameters, immunohistochemical biomarker and other clinical factors were performed using the Kaplan-Meier method and Cox proportional hazards regression analysis. RESULTS: In univariate analyses, tumour stage, tumour size, and MTV were significant prognostic factors for decreased overall survival (OS) and disease-free survival (DFS). Multivariate analyses showed MTV and tumour stage were significant predictors of poor OS (MTV, hazard ratio (HR) = 1.135, p = 0.015; stage, HR = 0.644, p = 0.025) and DFS (MTV, HR = 1.128, p = 0.043; stage, HR = 0.541, p = 0.009). CONCLUSION: The MTV of primary tumours is a significant prognostic factor for survival along with tumour stage in patients with surgically resected NSCLC. The MTV can predict OS and DFS better than immunohistochemical biomarkers.

Antisense knockdown of the glial glutamate transporter GLT-1, but not the neuronal glutamate transporter EAAC1, exacerbates transient focal cerebral ischemia-induced neuronal damage in rat brain.

Transient focal cerebral ischemia leads to extensive neuronal damage in cerebral cortex and striatum. Normal functioning of glutamate transporters clears the synaptically released glutamate to prevent excitotoxic neuronal death. This study evaluated the functional role of the glial (GLT-1) and neuronal (EAAC1) glutamate transporters in mediating ischemic neuronal damage after transient middle cerebral artery occlusion (MCAO). Transient MCAO in rats infused with GLT-1 antisense oligodeoxynucleotides (ODNs) led to increased infarct volume (45 +/- 8%; p < 0.05), worsened neurological status, and increased mortality rate, compared with GLT-1 sense/random ODN-infused controls. Transient MCAO in rats infused with EAAC1 antisense ODNs had no significant effect on any of these parameters. This study suggests that GLT-1, but not EAAC1, knockdown exacerbates the neuronal death and thus neurological deficit after stroke.

Advanced management of arteriovenous shunting malformation with transarterial lung perfusion scintigraphy for follow-up assessment.

AIM: The clinical assessment of arteriovenous malformations (AVMs), including treatment response (surgical and/or embolosclerotherapy), has traditionally been done by arteriography, mainly by looking for residual lesions. However, arteriography is disadvantaged as it is an expensive invasive test with high morbidity and provides only limited anatomical information at the qualitative level. Here, transarterial lung perfusion scintigraphy (TLPS), which was developed as a less invasive test for the physiologic assessment of the arteriovenous shunting status of AVM lesions located in the lower extremities, was evaluated for its ability to replace traditional arteriography as a means of following-up treatment results. METHODS: The shunting volume of radioisotope-tagged macro-aggregated albumin injected into the arterial system of the affected limb was counted by TLPS before and after AVM treatment, as a quantitative measure of treatment response. The findings obtained were compared with a matching duplex scan, whole body blood pool scintigraphy (WBBPS) findings, and arteriographic findings. RESULTS: Twenty-one TLPS tests were performed as follow-up assessments on 15 patients with AVM in the extremity, who underwent multistaged embolo/sclerotherapy alone or combined with surgical therapy. These 21 TLPS findings, including 6 interim TLPS results (average 16 months follow-up), provided quantitative measurements of lesion reductions as percentile ratios versus the baseline pretreatment values. Matching posttreatment duplex scan (14 out of 17 sets) and WBBPS (12 out of 15 sets) findings confirmed the posttreatment TLPS assessment. RESULTS: In addition, all 12 available arteriographic studies confirmed the matching TLPS findings. CONCLUSIONS: TLPS can provide accurate information on shunting volume reduction, occurring in response to various treatments during or after the completion of therapy. TLPS, therefore, may be able to replace arteriography, and provide a reliable means of follow-up assessment for the determination of the future treatment strategy.

Sexual dimorphism in vertebral fragility is more the result of gender differences in age-related bone gain than bone loss.

Spine fractures usually occur less commonly in men than in women. To identify the structural basis for this gender difference in vertebral fragility, we studied 1013 healthy subjects (327 men and 686 women) and 76 patients with spine fractures (26 men and 50 women). Bone mineral content (BMC), cross-sectional area (CSA), and volumetric bone mineral density (vBMD) of the third lumbar vertebral body (L3) were measured by posteroanterior (PA) and lateral scanning using dual-energy X-ray absorptiometry (DXA). In this cross-sectional study, the diminution in peak vertebral body BMC from young adulthood to old age was less in men than in women (6% vs. 27%). This diminution was the net result of two opposing changes occurring concurrently throughout adult life: the removal of bone adjacent to marrow on the inner (endosteal) surface by bone resorption and the deposition of bone on the outer (periosteal) surface by bone formation. For L3, we estimated that men resorbed 3.7 g and deposited 3.1 g, producing a net loss of 0.6 g from young adulthood to old age and women resorbed 3.1 g and deposited only 1.2 g, producing a net loss of 1.9 g. Thus, based on our indirect estimates of periosteal gain and endosteal loss across life, the observed net diminution in BMC during aging was less in men than women because absolute periosteal bone formation was greater in men than women (3.1 g vs. 1.2 g) not because absolute bone resorption was less in men. On the contrary, the absolute amount of bone resorbed was greater in men than women (3.7 g vs. 3.1 g). Periosteal bone formation also increased vertebral body CSA 3-fold more in men than in women, distributing loads onto a larger CSA, so that the load imposed per unit CSA decreased twice as much in men than in women (13% vs. 5%). In men and women with spine fractures, CSA and vBMD were reduced relative to age-matched controls. However, vBMD was no different to the adjusted vBMD in age-matched controls derived assuming controls had no periosteal bone formation during aging. Thus, large amounts of bone are resorbed in men as well as in women, accounting for the age-related increase in spine fractures in both genders. Periosteal bone formation increases CSA and offsets bone loss in both genders but more greatly in men, accounting for the lower incidence of spine fractures in men than in women. We speculate that reduced periosteal bone formation, during growth or aging, may be in part responsible for both reduced vertebral size and reduced vBMD in men and women with spine fractures. Sexual dimorphism in vertebral fragility is more the result of gender differences in age-related bone gain than age-related bone loss.

Improved detection of individual nodal involvement in squamous cell carcinoma of the esophagus by FDG PET.

UNLABELLED: Because both the number and location of metastatic lymph nodes and the N stage influence survival in esophageal cancer, accurate noninvasive evaluation of individual lymph node groups for the presence of metastasis is essential for therapeutic planning. Therefore, we investigated the accuracy of FDG PET for evaluating individual lymph groups in esophageal cancer patients and compared the results with those of CT and endoscopic sonography (ES). METHODS: Sixty-one consecutive patients with histologically proven primary esophageal carcinoma were studied prospectively with FDG PET. Thirteen patients who were treated nonsurgically were excluded from data analysis. The remaining 48 patients underwent esophagectomy and lymph node dissection. All 48 patients underwent CT scanning, including the lower neck, thorax, and upper abdomen, with intravenous administration of contrast medium. ES was performed in 45 of the patients but was incomplete in 12 patients because of esophageal stenosis. The accuracies of FDG PET, CT, and ES were compared with histologic findings. RESULTS: During surgery, a total of 382 lymph node groups were dissected in 48 patients, of which 100 node groups in 32 patients were malignant on histologic examination. For assessing metastasis to individual groups, FDG PET showed 57% sensitivity, 97% specificity, and 86% accuracy, whereas CT showed 18% sensitivity (P < 0.0001), 99% specificity (P = 0.033), and 78% accuracy (P = 0.003). For N staging, FDG PET was correct in 83% (40/48) of the patients, whereas CT and ES were correct in 60% (29/48; P = 0.006) and 58% (26/45; P = 0.003), respectively. CONCLUSION: FDG PET is more accurate than is CT or ES for evaluating metastasis to individual lymph node groups and for N staging in esophageal cancer and thus may be helpful in determining the therapeutic plan.

Quantification of myocardial blood flow using 13N-ammonia and PET: comparison of tracer models.

UNLABELLED: Several tracer kinetic methods have been proposed for quantification of regional myocardial blood flow (MBF) with 13N-ammonia and PET. Merits and limitations specific to each approach, however, generally are not clear, because they have not been evaluated in the same experimental environment. Therefore, we compared six different commonly used methods (11 modifications) to characterize the accuracy of each approach. The methods included the two-parameter model (method 1), the modified two-parameter model (method 2), the four-parameter model (method 3), the graphical analysis (method 4), the first-pass extraction method (method 5) and the dose uptake index (DUI; method 6). METHODS: Eleven studies in four dogs, 16 studies in eight healthy human volunteers and 14 studies in seven patients were performed using 13N-ammonia and PET. MBF in dogs was varied with dipyridamole and coronary occlusions and was measured independently and simultaneously with microspheres. Volunteers and patients were studied at baseline and after dipyridamole. MBF and DUI were estimated using a time-activity curve (Qi[t]) derived from dynamic images and regions of interest (ROls) and using the six methods. DUI was defined as Qi(t = 2 min) x weight/dose. RESULTS: MBF estimated by methods 1-5 correlated well with microsphere MBF in dogs. MBF estimates by method 1 correlated well with those by methods 2, 4 and 5 and to a lesser degree with those by method 3 in both dog and human studies. DUI correlated poorly with MBF by microspheres and by methods 1-5 in both dog and human studies. MBF estimates by method 3 showed larger dispersion (SD/mean flow) and higher sensitivity to metabolites correction in arterial blood than those by methods 1, 2, 4 and 5. CONCLUSION: MBF can be measured accurately using 13N-ammonia PET and tracer kinetic methods. DUI is a poor indicator of MBF values. The results indicate that preference should be given to the two-parameter model, incorporating geometrical ROI representation (method 2) among the compartment models, and to the graphical analysis (method 4) among the noncompartmental approaches.

Usefulness of diabetic retinopathy as a marker of risk for thallium myocardial perfusion defects in non-insulin-dependent diabetes mellitus.

Among 236 non-insulin-dependent diabetics with clinically suspected coronary artery disease, the rate of thallium-201 myocardial perfusion defects was significantly higher in subjects with (40.6%) than without (22.1%) diabetic retinopathy. Retinopathy was associated with a higher risk of perfusion defects in subjects with cardiac and noncardiac chest pain, and may thus be a useful marker for selecting patients in whom thallium scintigraphy screening is warranted.

Purification and reaction mechanism of arylsulfate sulfotransferase from Haemophilus K-12, a mouse intestinal bacterium.

A novel type of sulfotransferase, arylsulfate sulfotransferase [EC 2.8.2.22], was purified to homogeneity from Haemophilus K-12, a mouse intestinal bacterium. The purified enzyme (M(r) 290,000) is composed of four subunits (M(r) 70,000). The best donor substrate was 4-methylumbelliferyl sulfate, followed by beta-naphthyl sulfate, p-nitrophenyl sulfate (PNS), and alpha-naphthyl sulfate. The best acceptor substrate was alpha-naphthol, followed by phenol and resorcinol. The apparent Km for PNS using phenol as an acceptor and that for phenol and resorcinol. The apparent Km for PNS using phenol as an acceptor and that for phenol using PNS as a donor substrate were determined to be 0.095 and 0.71 mM, respectively. One of the reaction products, p-nitrophenol inhibited the enzyme noncompetitively with respect to PNS, but competitively with respect to alpha-naphthol. The Ki values of PNP for PNS and alpha-naphthol were 0.89 and 0.12 mM, respectively. The other reaction product, alpha-naphthyl sulfate, inhibited the enzyme competitively with respect to PNS, but non-competitively with respect to alpha-naphthol. The Ki values of alpha-naphthyl sulfate for PNS and for alpha-naphthol were 2.72 and 1.7 mM. These results suggest that the sulfate transfer reaction proceeds according to a ping pong bi bi mechanism.

Purification and characterization of a novel heparinase from Bacteroides stercoris HJ-15.

A novel type of heparinase (heparin lyase, no EC number) has been purified from Bacteroides stercoris HJ-15, isolated from human intestine, which produces three kinds of heparinases. The enzyme was purified to apparent homogeneity by a combination of QAE-cellulose, DEAE-cellulose, CM-Sephadex C-50, hydroxyapatite, and HiTrap SP chromatographies with a final specific activity of 19.5 mmol/min/mg. It showed optimal activity at pH 7.2 and 45 degrees C and the presence of 300 mM KCl greatly enhanced its activity. The purified enzyme activity was inhibited by Cu(2+), Pb(2+), and some agents that modify histidine and cysteine residues, and activated by reducing agents such as dithiothreitol and 2-mercaptoethanol. This purified Bacteroides heparinase is an eliminase that shows its greatest activity on bovine intestinal heparan sulfate, and to a lesser extent on porcine intestinal heparan sulfate and heparin. This enzyme does not act on acharan sulfate but de-O-sulfated acharan sulfate and N-sulfoacharan sulfate were found to be poor substrates. The substrate specificity of this enzyme is similar to that of Flavobacterial heparinase II. However, an internal amino acid sequence of the purified Bacteroides heparinase shows significant (73%) homology to Flavobacterial heparinase III and only 43% homology to Flavobacterial heparinase II. These findings suggest that the Bacteroidal heparinase is a novel enzyme degrading GAGs.

Evaluation of lymph node metastases in squamous cell carcinoma of the esophagus with positron emission tomography.

BACKGROUND: Previous studies suggest positron emission tomography (PET) may improve staging accuracy of esophageal cancer compared with conventional methods, especially in detecting occult distant metastases. We evaluated the accuracy of PET in the detection of lymph node metastasis prospectively with pathologic findings. METHODS: Fifty-three patients with squamous cell carcinoma underwent whole-body PET scan and chest computed tomography (CT). The findings of PET and chest CT of 50 patients who underwent curative esophagectomy with radical lymph node dissection were compared with the pathologic findings. RESULTS: Among 53 primary esophageal tumors, PET detected 51 (96.2%) and CT detected 49 (92.5%) tumors correctly. Nodal metastases were present in 108 of 436 dissected lymph node groups. PET detected 56 metastatic node groups (51.9% sensitivity, 94.2% specificity, 83.7% accuracy), compared with CT, which detected 16 (14.8% sensitivity, 96.7% specificity, 76.6% accuracy; sensitivity: p < 0.005). CONCLUSIONS: PET was more sensitive than CT in the detection of nodal metastases and may improve staging of squamous cell carcinoma of the esophagus.

A simple and efficient in vitro method for metabolism studies of radiotracers.

In vitro metabolism of acetylcholinesterase inhibitors containing 3-[(18)F]fluoromethylbenzyl- ([(18)F]1) and 4-[(18)F]fluorobenzyl-piperidine moieties ([(18)F]2) was studied and compared with the in vivo metabolism. Defluorination of the [(18)F]1 mainly occurred to generate [(18)F]fluoride ion both in vitro and in vivo. In contrast, the [(18)F]2 was converted into an unknown polar metabolite in both metabolism methods and another metabolite, 4-[(18)F]fluorobenzoic acid in vitro. These results demonstrated that the in vitro method can be used to predict the in vivo metabolism of both radiotracers.

Morphometric aspects of extraforaminal lumbar nerve roots.

OBJECTIVE: In the posterolateral extraforaminal and anterolateral retroperitoneal approaches to lumbar spinal lesions, the neural structures in the lumbar extraforaminal region are unfamiliar to many spinal surgeons. The purpose of this study was to determine the normal anatomic morphometric parameters for all lumbar nerve roots around their exits, from the intervertebral foramen to the surrounding bony structure. METHODS: A total of 15 adult fixed cadavers were studied. The extraforaminal course of the lumbar nerve roots and the forming plexus were measured segmentally, using standard calipers, and we selected the shortest distance from the bony landmarks to the nerve roots in the horizontal plane. The bony landmarks were the most medial superior border of the transverse process (TP), the most medial inferior border of the TP, the tip of the superior articular process, and the most dorsolateral margin of the intervertebral disc space. In addition, the angle of each root exiting from the intervertebral foramen was measured using a goniometer. RESULTS: The mean distance from the medial superior border of the TP to the upper segment of the nerve root was 5.1 to 6.4 mm at L2-L5. The mean distance from the medial inferior border of the TP to the corresponding nerve root was 8.5 mm at L2 and L3 and 6 mm at L4 and L5. The mean distance from the tip of the superior articular process to the most dorsal border of the descending nerve trunk was 19 mm at L2 and L3 and 22 mm at L4 and L5. The main lumbar nerve trunk was located close to the most dorsolateral surface of the vertebral body and the intervertebral disc space, and it was topographically arranged dorsoventrally from the L5 to L2 nerve components. The average widths of the nerve trunk were 10, 14, and 25 mm at L3-L4, L4-L5, and L5-S1, respectively. The mean angles of the exiting roots in the extraforaminal region were 16 degrees at L2 and L3 and 25 degrees at L4 and L5. CONCLUSION: The lumbar nerve component, including both the lumbar trunk and each exiting nerve root in the extraforaminal region (the so-called "danger zone"), was located anteriorly at a distance more than 5 mm from the TP, more than 19 mm from the superior articular process, and up to 25 mm from the intervertebral disc space. Based on our results, the danger zone occupied up to 25 mm forward from the intervertebral foramen at the lower lumbar segments. Therefore, during operations such as percutaneous posterolateral procedures and open posterolateral or anterolateral approaches, great care should be taken within 25 mm of the extraforaminal region, especially for the lower lumbar spine.

Protective effects of glial cell line-derived neurotrophic factor on hippocampal neurons after traumatic brain injury in rats.

OBJECT: The purpose of this study was to evaluate whether glial cell line-derived neurotrophic factor (GDNF) can protect against hippocampal neuronal death after traumatic brain injury (TBI). METHODS: Male Sprague-Dawley rats were subjected to moderate TBI with a controlled cortical impact device while in a state of halothane-induced anesthesia. Then, GDNF or artificial cerebrospinal fluid ([aCSF]; vehicle) was infused into the frontal horn of the left lateral ventricle. In eight brain-injured and eight sham-operated rats, GDNF was infused continuously for 7 days (200 ng/day intracerebroventricularly at a rate of 8.35 ng/0.5 microl/hour). An equal volume of vehicle was infused at the same rate into the remaining eight brain-injured and eight sham-operated rats. Seven days post-injury, all rats were killed. Their brains were sectioned and stained with cresyl violet, and the hippocampal neuronal loss was evaluated in the CA2 and CA3 regions with the aid of microscopy. A parallel set of sections from each brain was subjected to immunoreaction with antibodies against glial fibrillary acidic protein (GFAP; astroglia marker). In the aCSF-treated group, TBI resulted in a significant neuronal loss in the CA2 (60%, p < 0.05) and CA3 regions (68%, p < 0.05) compared with the sham-operated control animals. Compared with control rats infused with aCSF, GDNF infusion significantly decreased the TBI-induced neuronal loss in both the CA2 (58%, p < 0.05) and CA3 regions (51%, p < 0.05). There was no difference in the number of GFAP-positive astroglial cells in the GDNF-infused rats in the TBI and sham-operated groups compared with the respective vehicle-treated groups. CONCLUSIONS: The authors found that GDNF treatment following TBI is neuroprotective.