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.

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.

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. OBJECTIVE: 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). METHODS: 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 ...

Unique features of non-obstructive emphysema and pure airway obstruction.

SETTING: Emphysema without airway obstruction or airway obstruction without emphysema are often detected clinically, although they are commonly co-existent. We therefore tested the hypothesis that non-obstructive emphysema and pure airway obstruction have unique features. METHODS: A case-control observation study was undertaken retrospectively in a patient cohort at a single centre. Among 2662 subjects who underwent chest computed tomography and pulmonary function tests, we enrolled 90 patients with non-obstructive emphysema, 119 with pure airway obstruction, 81 with obstructive emphysema and 2031 subjects as normal controls. The features of the four groups were analysed and compared. RESULTS: Higher serum homocysteine (13.4 ± 7.4 vs. 11.6 ± 4.6 mol/l), higher rate of osteoporosis (15.8% vs. 4.5%), higher leukocyte count, higher male ratio, lower serum albumin and lower body mass index were observed in subjects with non-obstructive emphysema than in controls (P < 0.05). In multiple logistic regression analysis of groups without airway obstruction, osteoporosis, hyperhomocysteinaemia, hypoalbuminaemia and higher leukocyte count were independent factors associated with non-obstructive emphysema (P < 0.05). CONCLUSION: Hyperhomocysteinaemia, hypoalbuminaemia, osteoporosis and higher leukocyte count were independent predictors of non-obstructive emphysema.

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.

The arcuate NPY, POMC, and CART expressions responding to food deprivation are exaggerated in young female rats that experienced neonatal maternal separation.

This study was conducted to examine the effect of neonatal maternal separation on the hypothalamic feeding peptides expression in young female offspring. Sprague-Dawley pups were separated from dam for 3h daily during PND 1-14 (MS), or left undisturbed except routine cage cleaning (NH). Weanling female pups were housed in group and the arcuate mRNA levels of neuropeptide Y (NPY), proopiomelanocortin (POMC), and cocaine-amphetamine regulated transcript (CART) were examined at two months of age with or without food deprivation. The basal arcuate expression levels of these peptides did not differ between NH and MS group. However, a 48 h of food deprivation significantly increased NPY mRNA level, and decreased POMC and CART, in the arcuate nucleus of MS females, but not in NH females. Fasting-induced elevation of the plasma corticosterone tended to be greater in MS group than in NH, but the basal levels did not differ between the groups. Plasma leptin levels were decreased in MS females compared with NH, and food deprivation significantly suppressed the leptin levels both in NH and MS groups. Results suggest that MS experience may increase stress vulnerability in female rats and exaggerate the feeding peptides expression in the arcuate nucleus responding to metabolic stress food deprivation.

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.

One-year prevalence and socio-cultural aspects of chronic headache in Turkish immigrants and German natives.

The aim of this research was to study the prevalence of chronic headache (CH) and associated socio-cultural factors in Turkish immigrants and native Germans. Five hundred and twenty-three Turkish and German company employees were screened using a standard questionnaire. Those who suffered from headaches were also examined by a neurologist. Complete data were available for 471 (90%) subjects. Thirty-four participants (7.2%) had CH. Two independent factors for association with CH could be identified: overuse of acute headache medication (OR = 72.5; 95% CI 25.9-202.9), and being a first-generation Turkish immigrant compared with native Germans (OR = 4.4; 95% CI 1.4-13.7). In contrast, the factor associated with chronic headache was not increased in second-generation Turkish immigrants. Medication overuse was significantly more frequent in first-generation Turkish immigrants (21.6%) compared with second-generation Turkish immigrants (3.3%) and native Germans (3.6%; chi(2) = 38.0, P < 0.001). First-generation Turkish immigrants did not contact headache specialists at all, compared with 2.8% of second-generation Turkish immigrants and 8.8% of native Germans (chi(2) = 118.4, P < 0.001). Likewise no first-generation Turkish immigrant suffering from CH received headache preventive treatment, compared with 6.6% of native Germans (chi(2) = 19.1, P = 0.014). The data from this cross-sectional study reveal a high prevalence of chronic headache as well as a very low utilization of adequate medical care in first-generation Turkish immigrants in Germany.

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.

Contemporary diagnosis and management of venous and arterio-venous shunting malformation by whole body blood pool scintigraphy.

AIM: Various non- to less-invasive tests have been recently introduced in the management of congenital vascular malformations (CVM) and have become essential for the initial diagnostic work-up, largely replacing the traditional role of invasive tests. Whole body blood pool scintigraphy (WBBPS) was initially adopted as a supplementary test to reinforce other well-established essential diagnostic tests, and has been used extensively together in our Clinic, for years. We have evaluated WBBPS retrospectively for the diagnosis of venous malformation (VM) and arterio-venous malformation (AVM), and also for a further possible role for the interim assessment of treatment results during multistaged embolo/sclerotherapy. METHODS: Of 123 VMs and 48 AVMs selected for various treatments, 80 patients (66 VMs and 14 AVMs) were reviewed. The reliability of WBBPS as an initial diagnostic tool for VMs and AVM was assessed first by comparing its findings with matching MRI and/or duplex scan findings. These 80 patients underwent embolo/sclerotherapy with absolute ethanol mostly for VM, and N-butyl cyanoacrylate for AVM. A total of 251 sessions were performed either as a primary treatment independently or in conjunction with surgical treatment preoperatively. Thirty-six patients were available in terms of the subsequent review of the treatment results, to compare their 72 post-therapy WBBPS findings with matching duplex scan and MRI findings. The WBBPS assessment of treatment response was based on the percentage reduction of abnormal blood pooling over the region of interest (ROI) from baseline (initial) value. Treatment response was also qualitatively and semi-quantitatively assessed according to the degree of abnormal blood pool reduction. RESULTS: Of the 80 CVM (66 VM and 14 AVM) patients, 61 of 66 WBBPS findings of VM on initial diagnosis were confirmed as true-positive. Twelve of 14 AVMs were also confirmed as WBBPS true-positive findings. The sensitivity of WBBPS for the initial diagnosis was 93.8% (61/65) for VM and 92.3% (12/13) for AVM. The positive predictive value was 98.4% (61/62) for VM and 92.3% (12/13) for AVM. Of 72 post-therapy WBBPS performed for follow-up assessment of the results of treatment on 36 patients, 52 WBBPS showed positive findings qualitatively and/or quantitatively, the remaining 20 were negative. Fifty-one of the 52 WBBPS-positive findings were true-positive and 18 of the 20 were true-negative. Hence, WBBPS for follow-up assessment showed a sensitivity of 96% (51/53); a specificity of 95% (18/19); a positive predictive value of 98% (51/52); and a negative predictive value of 90% (18/20). CONCLUSIONS: Contemporary management of CVMs can be improved by using WBBPS, which is a less expensive, simple, and safe non-invasive test, especially for venous and arterio-venous malformations. WBBPS is a cost-effective and practical test with dependable accuracy for the assessment of treatment results, especially for interim measurements during multistage embolo/sclerotherapy.

Cell uptake and tissue distribution of radioiodine labelled D-luciferin: implications for luciferase based gene imaging.

Optical luciferase gene imaging is emerging as a method to monitor gene expression in small animals. However, there is concern over how regional availability of exogenously administered substrate may affect photon emission. We thus synthesized [125I]iodo-D-luciferin, which demonstrated substrate characteristics for firefly luciferase, and investigated its cell uptake kinetics and in vivo biodistribution. Luminescence assays of luc gene transduced cells confirmed a linear decline in emitted light units with decreasing luciferin concentration. Both luc gene transduced and control cells demonstrated a low level of cellular uptake and rapid washout of [125I]iodo-D-luciferin, although early uptake was slightly higher for transduced cells (P < 0.005). Biodistribution in ICR mice demonstrated that early uptakes in liver, lung, myocardium and muscle were lower with intraperitoneal compared to intravenous administration. In view of the poor cell uptake, uptake levels (< 3%ID/g) suggest that substrate concentration may limit light emission rates in organs such as bone, muscle, myocardium, and particularly the brain. Thus, substrate availability should be considered as a potential limiting factor for photon emission efficiency in certain organs when attempting quantitative interpretation of optical luc gene imaging.

Determination of the prognostic value of [(18)F]fluorodeoxyglucose uptake by using positron emission tomography in patients with non-small cell lung cancer.

The aim of this study was to determine whether quantitative information obtained from [(18)F]fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) has a prognostic significance for patients with non-small cell lung cancer (NSCLC). We investigated (18)F-FDG PET imaging of 73 patients with NSCLC. The maximum standardized uptake value (SUV(max)) was significantly different between the histopathological types of tumour (squamous cell carcinoma (n=37, 12.4+/-5.1), adenocarcinoma (n=30, 8.2+/-5.8), bronchioloalveolar carcinoma (n=4, 2.6+/-1.7), <0.01). In the univariate analysis of all patients, staging (P=0.0001), tumour cell type (P=0.013), and a SUV(max) greater than 7 (P=0.0011) was correlated with survival. However, a multivariate analysis identified staging and SUV(max) greater than 7 were affected survival adversely. The mortality rate of patients with group I disease (stage I to stage IIIA) was 5.8 times lower than that of patients with group II disease (stage IIIB to stage IV). Patients with a high SUV(max) (> or =7) had a 6.3 times higher mortality than those with a low SUV(max)(<7). By multivariate analysis of patients with squamous cell carcinoma, only grouping affected survival (P=0.008, relative risk=4.3). In the case of adenocarcinoma, the SUV(max) (>10) correlated exclusively with poorer survival (P=0.031, relative risk=11.152). (18)F-FDG uptake correlated with survival in NSCLC. Especially in adenocarcinomas, the SUV(max) was complementary to other known prognostic factors.

Use of insulin to improve [18 F]fluorodeoxyglucose labelling and retention for in vivo positron emission tomography imaging of monocyte trafficking.

While 18F-FDG labelling of monocytes would allow in vivo trafficking with positron emission tomography (PET), present methods suffer from poor retention of radioactivity. We investigated the feasibility of utilizing insulin for improved [18F]fluorodeoxyglucose (18F-FDG) labelling. Separated human monocytes and lymphocytes were labelled with 18F-FDG with or without 3 h insulin pre-incubation. Insulin had no effect on lymphocyte labelling (21.4+/-0.8% vs 20.8+/-1.1% efficiency, P=NS). However, for monocytes, insulin pre-incubation led to a 169+/-9% increase in labelling efficiency (19.3+/-4.1 vs 32.5+/-1.8, P<0.05), without significant effects on cell activation or viability. Moreover, while only 57.7+/-4.8% and 40.4+/-5.6% of the 18F-FDG was retained at 1 and 3 h for controls, the retention rate increased to 91.6+/-2.1% (P=0.01) and 86.5+/-1.9% (P<0.01) after insulin pre-incubation. Improved 18F-FDG retention was accompanied by a 70.3+/-7.4% decrease in glucose-6-phosphatase activity (P=0.02). PET imaging of rats showing hepatic ischaemia-reperfusion injury demonstrated higher liver uptake for monocytes labelled after insulin treatment. Thus, insulin improves monocytic 18F-FDG uptake and retention, and may provide a feasible labelling method for PET imaging.

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.

4-Hydroxy-6-oxo-6,7-dihydro-thieno[2,3-b] pyrimidine derivatives: synthesis and their biological evaluation for the glycine site acting on the N-methyl-D-aspartate (NMDA) receptor.

Bioisostere approach has been shown to be useful to augment potency or to modify certain physiological properties of a lead compound. Based upon well documented bioisosterism, an isosteric replacement of benzene ring of 4-hydroxy-2-quinolone compound (L-695902) with a thiophene moiety was carried out to prepare the title compounds, 4-hydroxy-6-oxo-6,7-dihydro-thieno[2,3-b] pyrimidines 15. The resulting bioisosteric compounds 15 were evaluated for their antagonistic activity (binding assay) for NMDA receptor glycine site.