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Background In this study, we introduced a newly designed totally implantable device for long-term vascular access in rats and compared its efficacy, related complications, and cost-effectiveness with conventional exteriorized jugular vein catheters. Methods Forty adult male Sprague-Dawley rats, weighing 250–300 g, were equally divided into two groups (I and II) and all underwent jugular vein catheterization surgery. The totally implanted device was used in group I and conventional exteriorized catheters were used in group II. The functionality of each catheter was checked every 3 d and evaluation included vascular accessibility, patency, and infection. The weight of the animal and microbial culture from the wound and tube were also monitored. We analyzed the cause of vascular access failure and complications, both mechanical and infectious, and compared related variables. Results The proportions of 9-d patency and 30-d patency in group I were 90% (18/20) and 75% (15/20), respectively, and in group II 80% (16/20) and 35% (7/20), respectively. There was a statistically significant difference in 30-d patency. The rats in group II were more liable to involve vascular access failure because of catheter dislodgment and had a higher infection rate (P = 0.001). Daily body weight gain was also greater in group I than in group II (2.46 ± 0.59 g/d versus 1.84 ± 0.96 g/d; P = 0.02). Conclusions This newly designed and totally implanted device substantially increases the success rate of long-term venous access compared with conventional methods. It reinforces the merits of the subcutaneous port and a tethered swivel system and overall has better performance and reliability. Furthermore, given its low cost and the high level of effectiveness offered, this technology could be a powerful tool to be used in future translational medicine research, especially in cases of long-term intravascular administration.

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The S-allele of functional polymorphisms of the serotonin transporter (SERT) gene has been demonstrated to have lower transcriptional activity compared with the L-allele, which shows low expression of SERT in the brain. However, this finding cannot be consistently replicated in vivo. The aim of this study was to determine the availability of SERT based on SERT genotype. We also examined the relationship between brain-derived neurotrophic factor (BDNF) and the availability of SERT. Sixty-two healthy subjects were recruited. Each subject underwent single-photon emission computed tomography with I-ADAM (I-labeled 2-([2-({dimethylamino}methyl)phenyl]thio)-5-iodophenylamine) for imaging SERT in the brain. The specific uptake ratio was measured, and venous blood was drawn when the subject underwent single-photon emission computed tomography to evaluate BDNF levels and SERT genotype. All subjects expressed SERT genotypes that were consistent with a biallelic model, and 26 subjects had SERT genotypes that were consistent with a triallelic model. No differences in specific uptake ratio were detected in the midbrain, putamen, caudate, and thalamus based on the SERT genotype using the biallelic and triallelic models. Interestingly, The Pearson correlation coefficient revealed a positive correlation between BDNF and SERT availability. In particular, this relationship was observed in homozygous S-allele expression and a genotype with low functional expression (SaSa/SaLg) in the biallelic and triallelic models of SERT genotypes, respectively. This finding might explain why the SS genotype of SERT did not increase the risk of major depressive disorder in Asian populations and implicate an important role of BDNF in the patients, who has the SS genotype of the SERT gene.

Thirty-seven patients aged 36-75 years with cirrhosis of the liver secondary to chronic hepatitis were included in the study. They were divided into three groups according to the modified Child's classification for cirrhotic severity, where A = good, B = fair and C = poor. In addition, the patients were divided according to the presence or absence of each of the following: ascites, splenomegaly and oesophageal varices. Radionuclide-labelled solid meals were used to evaluate gastric emptying and the 14 C-urea breath test was used to detect Helicobacter pylori infection. Gastric emptying was represented by the gastric retention ratio of the solid meal at 90 min (RR90) and calculated using the following formula: the residual radioactivity within the region of interest (ROI) covering the whole stomach at 90 min divided by the initial radioactivity within the ROI at 0 min. We found that 75.7% (28/37) of the patients had abnormal gastric emptying and 45.9% (17/37) had H. pylori infection. No significant correlation was found between abnormal gastric emptying and H. pylori infection. There were no significant differences among the three groups regarding gastric emptying or H. pylori infection according to the modified Child's classification. However, the highest rates of abnormal gastric emptying and H. pylori infection were in patients in Child's class C. The differences in RR90 among patients with and without ascites, and patients with and without splenomegaly, were not significant (P > 0.05). However, there was a significant difference between the patients with and without oesophageal varices (P < 0.05). In addition, poor correlations (R 2 < 0.01) were found between RR90 and serum levels of bilirubin and albumin.

Fifty female patients with acute abdomen and suspected appendicitis but atypical findings were included in this study. After intravenous injection of Tc-99m HMPAO-labeled WBCs, serial anterior abdominal/pelvic images at 30, 60, 120, and 240 minutes were obtained by a gamma camera. Any abnormal localization of WBC accumulation in the right lower quadrant of the abdomen with equal to or greater than bone marrow activity was considered as a positive scan. Thirty patients had positive WBC scans and underwent laparotomy, 28 had proven appendicitis, and 2 were not related to appendicitis. Twenty patients had negative WBC scans, 2 patients underwent laparotomy and were proved to have appendicitis. The remaining 18 patients did not undergo surgery and revealed no evidence of appendicitis after follow-up. The overall sensitivity, specificity, accuracy, and positive and negative predictive values for WBC scans to diagnose appendicitis is 93.3%, 90.0%, 92.0%, 93.3%, and 90.0%, respectively. In conclusion, Tc-99m HMPAO-labeled WBC imaging provides a rapid and highly accurate method for diagnosis of appendicitis in female patients with equivocal clinical examinations.

An attempt was made to use 99 Tc m -d,l-cyclobutylpropylene amine oxime ( 99 Tc m -d,l-CBPAO) to label leukocytes. The radiochemical purity of 99 Tc m -d,I-CBPAO, labelling efficiency of leukocytes, cell viability of labelled leukocytes and stability of 99 Tc m -d,l-CBPAO-labelled leukocytes were calculated. In comparison with the commercial cell-labelling agent 99 Tc m -d,l-hexamethylpropylene amine oxime ( 99 Tc m -d,l-HMPAO), (1) the radiochemical purity of 99 Tc m -d,l-CBPAO was higher than that of 99 Tc m -d,l-HMPAO immediately after and 1, 2, 4, 6, 8 and 24 h after 99 Tc m labelling; (2) the labelling efficiency of 99 Tc m -d,l-CBPAO-labelled leukocytes was lower than that of 99 Tc m -d,l-HMPAO; (3) the viability of labelled white blood cells was high for both agents; and (4) the stability of 99 Tc m -d,l-CBPAO-labelled leukocytes was better than that of 99 Tc m -d,l-HMPAO after 1, 2, 4, 6, 8 and 24 h. In conclusion, although the labelling efficiency of 99 Tc m -d,l-CBPAO is lower, it is more stable than 99 Tc m -d,l-HMPAO and provides greater stability of 99 Tc m -d,l-CBPAO-labelled leukocytes. Therefore, 99 Tc m -d,l-CBPAO has the potential to replace 99 Tc m -d,l-HMPAO as a commercial leukocyte-labelling agent.

The purpose of this study was to analyse the biodistribution of rhenium-188 Lipiodol in rats with hepatic tumours following intrahepatic arterial injection to assess the potential of188Re-Lipiodol as a radiopharmaceutical for the treatment of hepatic tumours in humans. Twelve male rats with hepatic tumours were killed at 1 h, 24 h and 48 h after injection of approximately 7.4 MBq of188Re-Lipiodol via the hepatic artery. Samples of various organs were obtained and counted to calculate the tissue concentration. Radioactivity in the hepatic tumours was very high throughout this study, with a biological half-life of 122.9 h. Radioactivity in the normal liver tissue was also high, but was significantly lower than in the tumour. The biological half-life in the normal liver tissue was 31.7 h. The ratio of tumour concentration to the normal liver tissue concentration was 5.15 at 1 h and rose to 7.7 at 24 h and 10.84 at 48 h. The level of radioactivity in the lung was high at 1 h, and declined rapidly over time. The level of radioactivity in the kidney was moderate throughout the study. The radiation concentrations in muscle, spleen, testis, bone and whole blood were insignificant. We conclude that188Re-Lipiodol should be considered as a potential radiopharmaceutical for the intra-arterial treatment of hepatic tumours.

While abnormal gastric emptying has been widely reported in patients with diabetes, its clinical relevance is still uncertain. We conducted scintigraphic gastric emptying studies in patients with Type II diabetes mellitus who had symptoms suggestive of delayed gastric emptying in an attempt to evaluate the incidence of abnormal gastric emptying and to assess the clinical parameters of the different patterns of gastric emptying. Seventy male diabetic patients were included in the study. The patients were divided into four groups according to the results of liquid and solid gastric emptying: group 1, normal liquid and solid emptying (n = 22); group 2, normal liquid but delayed solid emptying (n = 30); group 3, delayed liquid but normal solid emptying (n = 7); group 4, delayed liquid and solid gastric emptying (n = 11). To assess clinical significance, we compared duration of disease, status of blood sugar control, presence or absence of vascular complications and of peripheral neuropathy among the four groups. Of the 70 patients, 18 (25.7%) showed delayed liquid gastric emptying and 41 (58.6%) delayed solid gastric emptying. There were no significant differences in the clinical parameters of the four groups, except that patients with good sugar control were likely to have normal liquid gastric emptying. Based on the results of this study, delayed solid gastric emptying is more common than liquid gastric emptying in symptomatic Type II diabetes mellitus patients. Of the different patterns of gastric emptying, delayed liquid gastric emptying with normal solid gastric emptying is the most unusual. For Type II diabetic patients with symptoms suggestive of delayed gastric emptying, both liquid and solid gastric emptying studies should be performed.

Gastrointestinal vasculitis is a recognized but frequently misdiagnosed complication of systemic lupus erythematosus. The authors investigated the usefulness of three-phase Tc-99m pyrophosphate abdominal scintigraphy for identifying areas of vasculitis in patients with systemic lupus erythematosus who have gastrointestinal symptoms (diarrhea or abdominal pain). Among patients with gastrointestinal symptoms, 62 of 82 (75%) patients showed positive scan results, suggesting gastrointestinal vasculitis. Among patients without gastrointestinal symptoms, 6 of 43 (13%) patients showed positive scan results. Although three-phase Tc-99m pyrophosphate abdominal scintigraphy cannot provide a definite diagnosis of vasculitis of the gastrointestinal tract, it is a noninvasive and convenient method for suggesting and monitoring gastrointestinal vasculitis.

Ischemia is thought to be a major component in the pathogenesis of foot problems. The authors use the Xe-133 wasthout methoe to evaluate the blood perfusion of muscle tissue in the lower legs of patients with noninsulin-dependent diabetes mellitus (NIDDM). Eighty-five male patients with NIDDM ranging in age from 51 years to 79 yearss (mean, 66.5 years) and 47 nondiabetic control males with a matched age ranging from 52 years to 82 years (mean, 64.5 years) were included in this study. None of the diabetics had a history or presentation of peripheral vascular disease in the lower limbs. The patients were separated into groups according to the duration of the disease and condition of blood sugar control. The Xe-133 washout method was performed in the anterior tibial muscle of all the subjects. According to a Student's t-test, the tissue perfusion were of significant difference between 1) NIDDM and normal controls (1.98±1.39 ml/100 g/minute versus 2.85±1.35 Ml/100 g/minute), 2) good and poor blood sugar control (2.36±1.58 versus 1.51±0.94), and 3) long and short disease durations (1.50±0.78 versus 2.35±1.63). It is concluded that the tissue perfusion in the lower legs of patients with NIDDM is significantly decreased and related to the duration of the disease and condition of blood sugar control. This may contribute to the high incidence of foot gangrene and limb loss in patients with NIDDM. The authors consider that the Xe-133 washout technique may prove to be a useful method both for the early detection of diabetic microangiopathy, as well as for research on the pathophysiology of the microvascular disturbances in patients with DM

Twenty-eight children ranging in age from 1-6 years (11 girls, 17 boys) with Kawasaki disease and, for comparison, 30 normal children ranging in age from 1-8 years (8 girls, 22 boys) without any cardiovascular disease were included in this study. The left ventricular functions of the children were evaluated by equilibrium multigated blood pooling ventriculography (EMBPV), which was performed after in vivo labeling of red blood cells using 10 mCi Tc-99m pertechnetate. Scintigraphy was performed using a digital gamma camera with the aid of an electrocardiogram gate. The left ventricular functions were determined by Fourier analysis of the time-activity curve in the left ventricles. The parameters of the left ventricular functions included: 1) systolic phase--[a] ejection fraction (EF), [b] ejection time (ET), [c] peak ejection rate (PER), and [d] first 1/3 ejection rate mean (1/3ERM), and 2) diastolic phase--[a] peak filling rate (PFR), [b] fast filling fraction (FFF), [c] time to peak filling rate (TPFR), and [d] first 1/3 filling rate mean (1/3FRM). The results showed that no significant differences existed between the two groups in any parameter of the left ventricular function. The authors suggest that the left ventricular functions in children with Kawasaki disease are not apparently impaired. The results were proven by the presentation of the EMBPV in this study.

In this study, we labelled Lipiodol with yttrium-90 and analysed the biodistribution in rats after intrahepatic arterial injection. An RP-18 column (E. Merck) was used to separate 90Y from strontium-90. 90Y was retained on the column, which had been pretreated with yttrium-selective extraction reagent, di(2-ethylhexyl) phosphate, while 90Sr was washed out. A hexadentate nitrogen-donor chelating ligand N,N,N',N'-tetrakis(2-benzymidazolylmethyl)-1,2-ethanediamine (EDTB) was synthesized by condensation of 1,2-benzenediamine and ethylene diamine tetra-acetic acid (EDTA). Lipiodol was covalently conjugated with EDTB. The final product was obtained by eluting the retained 90Y from the RP-18 column with EDTB-Lipiodol. Sixteen male rats (Sprague-Dawley) were sacrificed at 1 h, 24 h, 48 h and 72 h (four rats at each time) after injection of approximately 0.1 mCi 90Y-Lipiodol via the hepatic artery. Samples of liver, spleen, muscle, lung, kidney, bone, whole blood and testis were obtained and counted to calculate the tissue concentrations. In addition, labelling efficiency and in vitro stability were determined by ITLC methods. We found that at 1 h after intrahepatic injection, most of the radiotracer was retained in the liver, but it was eliminated gradually over a few days. The radioactivity level in the lung was fair at 1 h and remained at roughly the same level throughout the study. Radioactivity in the kidney and spleen reached a relatively high level at 24 h, but declined rapidly.(ABSTRACT TRUNCATED AT 250 WORDS)

Forty-four patients with non-insulin-dependent diabetes mellitus (NIDDM) were included in this study. Radionuclide-labelled solid meals were used to calculate gastric emptying times (GETs). The carbon-14 urea breath test (14C-UBT) was used to diagnose Helicobacter pylori (HP) infection. The patients were separated into groups according to the following two criteria: (1) HP infection was diagnosed on the basis of a 14C-UBT value ofor = 1.5; (2) the GET was defined as abnormal when it wasor = 117.1 min. The results showed that 61% (27/44) of the NIDDM patients had an HP infection, and 59% (26/44) had an abnormal GET. The incidence of abnormal GET in positive 14C-UBT patients (62%) was higher than that in negative 14C-UBT patients (56%). Similarly, the incidence of positive 14C-UBT in abnormal GET cases (62%) was higher than that in normal GET cases (56%). However, according to chi-square tests the differences were not significant. In conclusion, no significant relationship between HP infection and GET was found in patients with NIDDM.

The current evidence on effect of fluoridation in drinking water on bone is inconsistent. This study was undertaken to assess the effect of fluoride concentration in drinking water on bone mineral density (BMD) in Taiwanese women.The study subjects included 248 women agedor = 40 years who reside in naturally fluoridated and adjacent areas. The individual fluoride concentration of the drinking water and the BMD of the subjects' lumbar spines were assessed.Women aged 46-65 years living in areas which have fluoride levels0.6 mg/l (mean = 0.18 mg/l; n = 130) had slightly lower bone densities than women living in areas with levelsor = 0.6 mg/l (mean 0.98 mg/l, n = 118). Only the age groups 46-50 and 61-65 years proved to be statistically significant. After controlling for age and body mass index, the BMD of those who had a doseor = 1.0 mg/l is notably higher than the reference group (or = 0.6 mg/l). After stratification by menopausal status, fluoride appeared to have no association with bone density in postmenopausal women.The BMD of the subjects from the area with a fluoride dose1 mg/l were significantly higher than those from the reference group (fluoride0.6 mg/l) for premenopausal women. There is no significant association between BMD and fluoride for postmenopausal women in Taiwan.

The presented case is a 36-year-old woman with a history of systemic lupus erythematosus for 10 years. She had progressively painful swelling of the right index finger that later proved to be a rare case of tenosynovitis caused by Mycobacterium avium complex. Serial images of 3-phase bone scans, gallium scan, and magnetic resonance imaging demonstrate the area of involvement.

The aim of this study was to investigate the relationship between resting brain glucose metabolism and cognitive profiles in patients with remitted bipolar I disorder (BD-I) and bipolar II disorder (BD-II). We hypothesized that BD-I patients (compared to BD-II patients) would perform worse on tests of cognitive function because of abnormal metabolism in the prefrontal cortex and other mood-related brain areas.Thirty-four patients with remitted bipolar disorder (BD) (BD-I = 17, BD-II = 17) under treatment and 17 well-matched healthy controls received both fluorodeoxyglucose ((18) F-FDG) positron emission tomography (PET) and neuropsychological tests of attention, memory, and executive function.Clinical features in patients with BD-I and BD-II were comparable. Executive function, as indicated by performance on the Wisconsin Card Sorting Test, was significantly worse (i.e., higher percentage of errors, lower percentage of conceptual level responses, and fewer categories completed) in BD-I patients than in BD-II patients and healthy subjects. No difference in attention and memory tests was found among these three groups. Brain PET analysis showed that BD-I patients (compared to BD-II patients) had significantly lower glucose uptake in the bilateral anterior cingulum, insula, striatum, and part of the prefrontal cortex, and higher glucose uptake in the left parahippocampus. Further analyses revealed significant correlations between poor executive function and abnormal glucose uptake in other brain areas in BD-I patients.There are neurobiological differences between subtypes of BD. BD-I is associated with more impaired fronto-limbic circuitry, which might account for reduced executive function in BD-I patients during remission.

The boron concentration (BC) in the blood, rather than in normal tissue, is often used as the reference to calculate the BC in tumor for boron neutron capture therapy (BNCT). The aims of this study were to justify whether BC in the blood is equal to that of normal tissue, and to verify the macro- and microdistributions of boron in tumor.BALB/c nude mice bearing SAS human oral carcinoma xenografts were intravenously injected with 400 mg/kg of boronophenylalanine (BPA). Macro- and microdistributions of boron in the tumor were assayed with (18)F-fluoro-L-boronophenylalanine-fructose (FBPA-Fr)/micro-positron-emission tomography (PET) and alpha track autoradiography, respectively.The BCs assayed from the blood, normal tissue and tumor varied even on sampling at the same time points post-BPA administration. The ratio of BC in normal tissue to that in blood, i.e. N/B ratio, remains about 1.31 at 30 to 45 min post-BPA administration. Furthermore, (18)F-FBPA-Fr/micro-PET imaging and autoradiography also showed heterogeneous boron distribution in the tumor.The heterogeneous distribution of boron in the tumor is a limiting factor for the precise calculation of BC in the tumor. Here we suggest that the N/B ratio could be used to calculate the true BC in the tumor and in normal tissue for BNCT. (18)F-FBPA-Fr/PET imaging is useful to justify the N/B ratio for BNCT treatment.

A copolymer of poly(ethylene glycol)-b-poly(caprolactone) (PEG-PCL) was modified with a benzyl moiety and labeled with I-131. A micelle system, (131)I-benzyl-micelles, formed from (131)I-benzyl-PEG-PCL and PEG-PCL-PC, was created and used for in vitro characterization and in vivo evaluation. Administration of (131)I-benzyl-micelles to a colon carcinoma-bearing mouse model gives a 4.9-fold higher tumor-to-muscle ratio at 48 h post-injection than treatment with the unimer (131)I-benzyl-PEG-PCL. Scintigraphic imaging, biodistribution results and pharmacokinetical evaluation all demonstrated that (131)I-benzyl-micelles are a plausible radioactive surrogate for PEG-PCL copolymer micelles. Modifying the amphiphilic copolymer with a benzyl moiety and labeled it with iodine-131 should make possible the real-time and noninvasive evaluation of the pharmacokinetics of copolymer micelles in vivo.

Thirty male patients, ranging in age from 41-78 years, with esophageal carcinomas underwent Tc-99m MIBI SPECT of the chest to evaluate the value of Tc-99m MIBI in the detection of esophageal carcinoma. In addition, Tc-99m MIBI SPECT of the chest was performed, for comparative purposes, in 10 normal patients who were referred because of suspected ischemic heart disease. Of the 30 patients with esophageal carcinoma, 22 epidermoid carcinomas (73%) were detected using Tc-99m MIBI chest SPECT, while eight carcinomas (27%) were not detected. In comparison, 10 of the control patients (100%) were not detected on the Tc-99m MIBI chest SPECT. In addition, the diagnostic sensitivity was not related to cell differentiation, the location, or the size of the carcinomas. These results suggest that the Tc-99m MIBI chest SPECT could be a helpful test to detect esophageal carcinoma.

The purpose of this study was to evaluate the value of bone and Ga-67 imaging in patients with malignant fibrous histiocytoma (MFH). Thirty-four patients with biopsy-proven MFH were studied. Of these patients, 15 underwent Ga-67 imaging, 26 underwent Tc-99m MDP imaging, and 7 underwent both imaging procedures. In evaluation of the primary tumors, intense Ga-67 uptake was observed in 14 of 15 patients with a diagnostic sensitivity of 93.3%. However, positive bone imaging results were observed in only 10 of 26 patients with a diagnostic sensitivity of 38.5%. Most of these were secondary to Tc-99m MDP uptake in adjacent bone invaded by the primary tumor. Only two patients, of the 18 patients without direct bone invasion, had increased radioactivity in the tumors (11.1%). In evaluation of the metastatic lesions, increased Ga-67 uptake was observed in 8 of 8 metastatic sites (100%). However, Tc-99m MDP could only detect 5 of 12 metastatic sites (41.7%), which were all diagnosed to be bone metastases. None of the extraskeletal metastasis could be detected by Tc-99m MDP imaging. Ga-67 scintigraphy appears to be a very useful tool in the evaluation of both primary and metastatic lesions of MFH and is assumed to be useful in the follow-up. However, it is emphasized that bone scintigraphy is useful only when the tumor invades the skeletal system and is of limited value in the evaluation of extraskeletal lesions.

Twenty-one patients with acute state Kawasaki disease (15 boys, 6 girls; age range, 1-8 years) had equilibrium multigated blood pool ventriculography (EMBPV) before treatment. The symptoms and signs subsided after the administration of aspirin and the intravenous injection of high-dose (400 mg/kg per day x 5 days) gamma-globulin (IVGG) treatment. Then, a second EMBPV was arranged to evaluate the effects of the treatment on left ventricular functions. Left ventricular function was analyzed based on the following parameters: (systolic phase) ejection fraction, ejection time, peak ejection rate, first 1/3 ejection rate mean; and (diastolic phase) peak filling rate, fast filling fraction, time to peak filling rate, first 1/3 filling rate mean. The results showed that there were no significant differences in the parameters of left ventricular function before and after treatment (P > 0.05, paired Student's t-tests).

Two children were diagnosed with viral encephalitis, due to Epstein-Barr virus infection in one case and to herpes simplex virus infection in the other. Tc-99m HMPAO brain SPECT was arranged to detect changes in regional cerebral blood flow (rCBF) secondary to viral encephalitis. During the acute episode, Tc-99m HMPAO brain SPECT showed that the two cases had increased rCBF. After the acute episode, follow-up brain SPECT was arranged 6 months later. The rCBF in one case was restored to normal on the second brain SPECT, and that in the other case was decreased. The child with normal rCBF in the follow-up brain SPECT had better learning ability and intelligence than the other child with decreased rCBF.

Radionuclide gastric emptying studies, including solid and liquid phases, were used to evaluate the gastric motility of healthy Chinese. Forty-eight patients (18-76 years old) and 38 volunteers (27-79 years old) accepted solid or liquid food gastric emptying studies, respectively. The solid meal was two fried eggs mixed with 500 microCi Tc-99m phytate and two pieces of toast to form a sandwich. The liquid meal was 500 ml of water with 5% glucose and 500 microCi Tc-99m phytate. Studies were performed with the subjects in the supine position and a gamma camera in a left anterior oblique (LAO) position while data were collected for 90 minutes and 30 minutes after finishing the solid and liquid meal, respectively. The gastric emptying time was presented as a half-time (t1/2) of the food emptying from the stomach. The study results showed that the t1/2 is 89.0 +/- 17.8 in older patients (60 years old) and 88.0 +/- 18.2 in younger patients (or = 60 years old) for the solid phase studies (P0.05), and that the t1/2 is 46.2 +/- 11.1 in older patients (60 years old) and 31.9 +/- 11.3 in younger patients (or = 60 years old) for the liquid phase studies (P0.05). We concluded that the age effects of gastric emptying in healthy Chinese occurred only in the liquid phase.

Candidiasis is the fourth most common bloodstream infection in hospitalized patients in the United States. Moreover, the mortality rate from Candida infections remains high, even after treatment with antifungal therapy. Vaccination would be a promising strategy for prevention of invasive fungal infections. In order to examine the main trends in anticandidal vaccine patenting activity, we conducted an analysis for anticandidal vaccine patents. We find 190 issued patent and 940 patent application documents containing the keywords Candida and vaccine within claims in the USA. Candida vaccines development, as evidenced by the numbers of issued patents, has decreased since the year 2002. Furthermore, the number of patent applications in Candida vaccines may indicate the strength of engaged resources were also in the status of stagnation during 2005-2007 and even a decline in 2008. Academic and nonprofit research institutions not only account for a large share of Candida vaccines patents but also apply for patents continually. Based on this analysis, the strength of Candida vaccines resources seems to remain stagnant in recent years due to patent prosecution or technical barrier in the filed of Candida vaccines. Therefore, we consider that Candida vaccines technology to still be under development and the researchers are still looking for scientific breakthrough in the filed.

Cancer vaccine targeting cancer stem cells is proposed to serve as a potent immunotherapy. Thus, it would be useful to examine the main trends in stem cell patenting activity as a guide for those seeking to develop such cancer vaccines. We found that a substantial number of stem cell patents were granted up to the end of 2010, including ~2000 issued in the US. Many of these have been filed since 2001, including 7,551 applications in the US. Stem cell development, as evidenced by the numbers of PubMed articles, has matured steadily in recent years. However, the other metrics, such as the number of patent applications, the technology-science linkage and the number of patent assignees, have been stagnant. Moreover, the ownership of stem cell patents is still quiet fragmented across multiple organizations, and the number of stem cell patent assignees from the business sector has not increased significantly. Academic and nonprofit institutions not only account for a large share of stem cell patents but also apply for patents continually. Based on this analysis, the strength of stem cell resources seems to remain stagnant in recent years due to the ban on government funding of embryonic stem cell research. Furthermore, the patent prosecution or technical barriers in the field of stem cells would be another main reason that the number of US-issued stem cell patents for each application have been in gradual decline since 2000. Therefore, we consider stem cell technology to still be under development.

Introduction Serotonin transporter (SERT) has been associated with many psychiatric diseases. This study investigated the biodistribution of a serotonin transporter imaging agent, N,N -dimethyl-2-(2-amino-4- 18 F-fluorophenylthio)benzylamine (4-[ 18 F]-ADAM), in nonhuman primate brain using positron emission tomography (PET). Methods Six and four Macaca cyclopis monkeys were used to determine the transit time (i.e., time necessary to reach biodistribution equilibrium) and the reproducibility of 4-[ 18 F]-ADAM biodistribution in the brain, respectively. The sensitivity and specificity of 4-[ 18 F]-ADAM binding to SERT were evaluated in one monkey challenged with different doses of fluoxetine and one monkey treated with 3,4-methylendioxymethamphetamine (MDMA). Dynamic PET imaging was performed for 3 h after 4-[ 18 F]-ADAM intravenous bolus injection. The specific uptake ratios (SURs) in the midbrain (MB), thalamus (TH), striatum (ST) and frontal cortex (FC) were calculated. Results The distribution of 4-[ 18 F]-ADAM reached equilibrium 120–150 min after injection. The mean SURs were 2.49±0.13 in MB, 1.59±0.17 in TH, 1.35±0.06 in ST and 0.34±0.03 in FC, and the minimum variability was shown 120–150 min after 4-[ 18 F]-ADAM injection. Using SURs and intraclass coefficient of correlation, the test/retest variability was under 8% and above 0.8, respectively, in SERT-rich areas. Challenge with fluoxetin (0.75–2 mg) dose-dependently inhibited the SURs in various brain regions. 4-[ 18 F]-ADAM binding was markedly reduced in the brain of an MDMA-treated monkey compared to that in brains of normal controls. Conclusion 4-[ 18 F]-ADAM appears to be a highly selective radioligand for imaging SERT in monkey brain.

We aimed to study whether positron emission tomography/computed tomography (PET/CT) findings are associated with lymph node staging, as outlined by the 7th edition American Joint Committee on Cancer (AJCC) TNM staging system in patients with esophageal squamous cell carcinoma (ESCC). A series of 76 ESCC patients undergoing esophagectomy were included in this study. The relation between PET/CT findings [maximum standardized uptake value (SUVmax)] and pathologic lymph node status (N stage) was studied. The SUVmax of extra-tumor uptake, but not that of the main tumor, was significantly associated with the N classification. N2/N3 disease was observed in 61.1% of patients with an SUVmax for extra-tumor uptake of >4.9, whereas only 17.2% of patients with an SUVmax of extra-tumor uptake of

PURPOSE Pulmonary sclerosing hemangioma (PSH), or the alternative name of "sclerosing pneumocytoma," is a rare benign neoplasm. PSH is often asymptomatic and presents as a solitary pulmonary nodule on radiologic imaging studies. Few articles have been reported to describe the FDG PET findings about PSH. We reported FDG PET findings of 6 cases of PSH and reviewed the literatures. MATERIALS AND METHODS FDG PET and PET/CT imaging studies of 6 patients with proven PSH were reviewed. The relation between the degree of FDG uptake and tumor size was analyzed. RESULTS All 6 tumors were detected by FDG PET or PET/CT. Mean diameter of these tumors was 2.9 cm. Mean standard uptake value was 2.45 (range, 1.8-3.93). The maximal standard uptake value of FDG uptake was positively correlated with the tumor size (R = 0.9694, P < 0.05). CONCLUSIONS PSH demonstrates low to moderate uptake on FDG PET imaging. The larger PSH has higher uptake and might be misrecognized as a malignancy. The possibility of false-positive result caused by PSH should be considered while interpreting FDG PET images of solitary pulmonary nodules.

To reduce positron emission tomography (PET) and computed tomography (CT) misalignments and standardized uptake value (SUV) errors, cine average CT (CACT) has been proposed to replace helical CT (HCT) for attenuation correction (AC). A new method using interpolated average CT (IACT) for AC is introduced to further reduce radiation dose with similar image quality. Six patients were recruited in this study. The end-inspiration and -expiration phases from cine CT were used as the two original phases. Deformable image registration was used to generate the interpolated phases. The IACT was calculated by averaging the original and interpolated phases. The PET images were then reconstructed with AC using CACT, HCT and IACT, respectively. Their misalignments were compared by visual assessment, mutual information, correlation coefficient and SUV. The doses from different CT maps were analyzed. The misalignments were reduced for CACT and IACT as compared to HCT. The maximum SUV difference between the use of IACT and CACT was ~3%, and it was ~20% between the use of HCT and CACT. The estimated dose for IACT was 0.38 mSv. The radiation dose using IACT could be reduced by 85% compared to the use of CACT. IACT is a good low-dose approximation of CACT for AC.

The patent information is the largest, well-classified and most up-to-date collection of technical documents on new and innovative technologies. To delicately exploring all the patent documents on the topic interested, we develop a thought process to precisely target and completely cover the patent documents interested. The tips on the process include expanding the keywords with synonyms and equivalents, limiting the search in a short period of time, keeping out the keywords not interested, identifying other possible keywords to screen the patent owned by the leading assignees or inventors, and inspecting other possible International Patent Classification (IPC) or United States Patent Classification (UPC). Following the thought process, we build a comprehensive patent search on human vaccine. Certainly, the search result searched should be updated frequently to keep the up-to-date information.

In order to demonstrate the possibility of design-around for patents, we reviewed 40 no-infringement cases out of all 4,760 Federal Circuit Court of Appeals (CAFC) cases decided from 2001 to 2009. Based on this analysis, designing around a biotechnology patent first requires a thorough reading of the patent specification and prosecution history. These written descriptions offer explicit directions about claim meanings or the scope being disclaimed. By statute, claims recite and define the structure or acts of an invention, and serve as tools to determine whether or not a patent is infringed. The next procedure would include omitting a part or property from the claim, reversing the action used in the claim, or changing the claim's structure or range to prevent the new design from falling within the scope of the claim. However, cases where patent infringement was found demonstrated that changing the structure or range not recited in the claim, such as enlarging the diameter, reducing concentration or alerting the shape, still falls within the scope of the patent. Although the 40 cases analyzed in this study were not related to vaccines, the thought process can serve as a guideline for patents related to vaccine development.

The hepatic perfusion index (HPI) in patients with hepatocellular carcinoma (HCC) and the correlation between HPI and survival was assessed. From September 1989 to March 1990, 36 patients with HCC and 32 normal volunteers underwent dynamic hepatic scintigraphy to estimate the HPI. Serum alpha-fetoprotein (AFP) and tumour size were also evaluated in all patients. A HPI > or = 0.85, AFP > or = 3000 ng ml-1 and tumour size > or = 8 cm chosen were as the cutoff points to obtain the highest differences in predicting survival. The HPI in HCC patients was significantly higher than in the normal controls (P < 0.0001). Survival was significantly different according to different HPI, AFP and tumour size with P < 0.0001, P = 0.007 and P = 0.01, respectively. It is concluded that the HPI is significantly elevated in patients with HCC. In addition, it is a useful prognostic factor and superior to AFP and tumour size in predicting the survival of patients with HCC.

To introduce our preliminary experience of treating locally and regionally recurrent Head and Neck cancer patients at Tsing Hua Open-Pool Reactor in Taiwan, four patients (M/F=3/1, median age 68 Y/O) were enrolled. BNCT with BPA (400 mg/kg) injected in 2 phases and prescription dose of 12-35 Gy (Eq.)/fraction for 2 fractions at 30 day interval can be given with sustained blood boron concentration and tolerable early toxicities for recurrent H & N cancer.

Previous brain imaging studies have demonstrated a seasonal difference of serotonin transporter (SERT) binding in the human brain. However, the results were somewhat contradictory. We conducted test-retest study with single photon emission computed tomography (SPECT) with ¹²³I-ADAM as ligand in 28 healthy subjects. Ten of the subjects were studied within 1 month, whereas 18 were randomly assigned to be studied over a period of up to 1 year. The primary measure was the specific uptake ratio (SUR). Regions of interest included the midbrain, thalamus, putamen and caudate. The intra-class correlation coefficient (ICC) was 0.52-0.94 across different brain regions over 1 month, whereas the ICC was -0.24-0.63 over a 1-year period. The 1-month variability ranged from 6.5 ± 5.1% to 12.5 ± 10.6% across different brain regions, and the 1-year variability ranged from 16.5 ± 9.6% to 41.9 ± 35.5%. The Kruskal-Wallis test revealed a significant difference of variability across months. The Wilcoxon Signed Ranks Test showed the SUR between test-retest scans was of borderline significance. Curve fitting, using a 4th degree polynomial model, revealed a significant circadian correlation between the variability and interval of test-retest measurements. Our findings demonstrate the test-retest reproducibility of ¹²³I-ADAM in different time periods and suggest that circadian variation of SERT levels in the human brain might exist.

Hearing impairment is one of the most common disorders in children. However, the hearing impairment is difficult to be monitored due to the limited availability of test equipments and trained specialists in many developing countries. The purpose of this study is to develop a novel method for quick hearing assessment of school-aged children. The proposed method is easy use and does not need to be operated by trained staff. Therefore, the parents or school nurses can routinely monitor the hearing level for the school-aged children. The proposed method could therefore be useful in monitoring progressive hearing change in a home-care setting.

Previous positron emission tomography studies have demonstrated that serotonin transporter (SERT) binding in the midbrain is decreased in the depressive state of bipolar disorder (BD). The aim of this study was to assess SERT binding in the midbrain of patients in a euthymic state of BD.Twenty-eight healthy controls and 24 patients in a euthymic state of medicated BD were recruited. Euthymic state was defined as Montgomery-Asberg Depression Rating Scale scores10 and Young Mania Rating Scale scores7 within a consecutive eight-week period. Single photon emission computed tomography with the radiotracer (123)I-ADAM was used to measure SERT binding in the midbrain. An equilibrium ratio model was used for data analysis. Specific uptake ratio (SUR), which represents availability of SERT binding in the midbrain, was the primary measurement outcome.The averaged SURs were not different between healthy controls and BD patients in euthymic state (p = 0.27). However, a three-way ANCOVA analysis comparing SURs in healthy controls, bipolar I disorder (BD I) patients, and bipolar II disorder (BD II) patients, covarying education duration and sex, showed that the averaged SURs were significantly lower in BD I than BD II patients and healthy controls (p = 0.042). The decreased SURs in BD I patients were well correlated with duration of illness (R = -0.742, p = 0.014) only.Our findings demonstrate that there is differential biological regulation in BD I and BD II patients after stable treatment, which may support the existence of a dichotomy in BD.

Background Add-on repetitive transcranial magnetic stimulation (rTMS) is effective in treating medication-resistant depression (MRD), but little is known about the rTMS antidepressant mechanism and pathophysiology underlying MRD. Methods Twenty MRD patients received 2 weeks of navigated add-on rTMS to the left dorsolateral prefrontal cortex (DLPFC). Treatment response was defined as a ≥ 50% decrease in HDRS after treatment. Cerebral glucose metabolism was measured from all MRD patients twice, before and 3 months after rTMS, and from 20 healthy controls once at baseline. Results At baseline, MRD subjects presented significant hypometabolism at the bilateral DLPFC and anterior cingulum, as well as hypermetabolism at several limbic and subcortical regions compared to the controls. Higher metabolism at the medial PFC and rostral anterior cingulum, and lower metabolism at the limbic structures, including the left parahippocampus and fusiform gyrus, predicted a response to rTMS. After successful rTMS treatment, the abnormally elevated metabolism in the left middle temporal cortex and fusiform gyrus decreased significantly, suggesting a reversal of metabolic imbalances. However, the overall metabolic pattern was still abnormal, even after their depression was under control. In contrast, the non-responders showed a worsening pattern of increased metabolism in the bilateral temporal cortex and fusiform gyrus. Conclusions The antidepressant mechanism of add-on rTMS may be reflected as suppression of hyperactivity in the left temporal cortex and fusiform gyrus, perhaps through enhancing the function of the medial prefrontal cortex and anterior cingulum. The limbic-cortical dysregulation of glucose metabolism might be a trait of an underlying mechanism of MRD.

The aim of the study was to propose an eccentricity parameter (EP)-based correction to the ellipsoid formula to improve the evaluation of the prostate volume defined by transabdominal ultrasonography (TAUS) at different stages of benign prostatic hyperplasia (BPH). All 202 adult male volunteers underwent the prostate volume evaluations with TAUS and computerized tomography (CT). Based on the EP index, three clearly different stages of BPH were also deduced by analytical analysis. By applying the correction formula, the mean prostate volume differences of TAUS with CT were improved from 28.1%, -25.4% and -0.6% to 7.6%, -3.5% and -0.6% for EP0.055, 0.055EP0.14 and EP0.14, respectively. Hence, for EP0.14, representing the advanced stage of BPH, TAUS with the ellipsoid formula can be regarded as an effective tool for computing volume, whereas for EP0.14, the correction formula is recommended to improve the volume estimation based on TAUS.

Fifty patients (43 male, 7 female, age 31-77 years) with single solid masses in their lungs based on the findings of a chest X-radiograph [40 malignancies: 5 small cell carcinoma (Ca), 17 epidermoid Ca, 12 adeno Ca, 6 undifferentiated large cell Ca] and 10 benign lesions underwent technetium-99m (V) dimercaptosuccinic acid [99m-(V)DMSA] scans to evaluate the usefulness of 99mTc-(V)DMSA in the detection of lung Ca with different cell types and benign lesions. Only 43% (17/40) of the malignancies in the lungs were detected by 99mTc-(V)DMSA, including 29% (5/17) epidermoid Ca, 50% (6/12) adeno Ca and 17% (1/6) undifferentiated large cell Ca of the lungs. However, all 5 cases of small cell Ca and 11 cases combined with bone metastasis were revealed by 99mTc-(V)DMSA. In addition, 3 of the 10 benign lesions (2 organizing pneumonias, 1 benign tumor) presented with an uptake of 99mTc-(V)DMSA. The diagnostic sensitivity, specificity and accuracy were 43%, 70% and 48%, respectively, in differentiating malignant from benign lesions for the single solid mass in the lungs. In conclusion, 99mTc-(V)DMSA is of little or no use in the differentiation of lung Ca from single solid masses in the lungs.

Myocardial imaging with Tc-99m HMPAO WBC was used to detect myocarditis of Kawasaki disease in 103 infants and children (66 boys and 37 girls, mean age 3 years and 4 months). The clinical course of Kawasaki disease may be divided into three phases, from the onset of illness onset until all clinical symptoms and signs have disappeared. Twenty-four hour myocardial imaging was performed in anterior, LAO, and left lateral views. The grading system was as follows: score 0 less than bone uptake; 1 = bone uptake; 2 greater than bone uptake; and 3 greater than or equal to liver uptake. If the score was greater than or equal to 2, significant myocarditis was considered. The appearing ratio of myocarditis was 57% (13/23) in the first phase; 65% (15/23) in the second phase; 54% (31/57) in the third phase. No significant difference was demonstrated among the three groups of patients (P greater than 0.1, by Chi-square test). In conclusion, an occult myocarditis may continue in all three phases of Kawasaki disease, even if the clinical symptoms and signs had improved by the evidence of Tc-99m HMPAO labeled WBC scan to avoid advanced cardiac complication.

Purpose: Tc-99m albumin scintigraphy is a noninvasive method for detecting protein-losing gastroenteropathy. Methods: Seven patients with protein-losing gastroenteropathy were evaluated with Tc-99m albumin scintigraphy. In addition, Tc-99m albumin scintigraphy was used to monitor the effect of treatment in five of these seven patients. The scintigraphic results were compared with serum albumin levels. Results: All seven patients had positive results in the pretreatment images. Changes in scintigraphic findings in the five treated patients correlated well with changes in serum albumin level. Conclusion: Tc-99m albumin scintigraphy is useful not only for diagnosing protein-losing gastroenteropathy but also for monitoring the effect of treatment.

An analysis of US Federal Circuit decisions shows the effects of the Supreme Court's decision in KSR v. Teleflex.

Liposomes modified with a high concentration of polyethylene glycol (PEG) could significantly prolong the retention time of the carried drug in the circulation, thus improving the drug accumulation in the tumor. In this study, 6 mol% rather than 0.9 mol% PEGylated liposomes (100 nm in diameter) encapsulated with indium-111 were used in a human colorectal carcinoma HT-29/luc tumor-bearing mouse model for comparing the PEGylation effect. Pharmacokinetics, biodistribution, passive-targeted assay, bioluminescence imaging (BLI) and tumor growth measurements were used for the spatial and temporal distribution, tumor localization and therapeutic evaluation of the drug. Pharmacokinetic studies indicated that the terminal half-life (T((1/2))lambdaz) and C(max) of 6 mol% PEG (111)In liposomes were similar to those of 0.9 mol% PEG (111)In liposomes. In the blood, the total body clearance (Cl) of 6 mol% PEG (111)In liposomes was about 1.7-fold lower and the area under the curve (AUC) was 1.7-fold higher than those of 0.9 mol% PEG (111)In liposomes. These results showed that the long-term circulation and localization of 6 mol% PEGylated liposomes was more appropriate for use in the tumor-bearing animal model. In addition, the biodistribution of 6 mol% PEG (111)In liposomes showed significantly lower uptake in the liver, spleen, kidneys, small intestine and bone marrow than those of 0.9 mol% PEG (111)In liposomes. The clearance rate of both drugs from the blood decreased with time, with the maximum at 24 h post intravenous (i.v.) injection. Prominent tumor uptake and the highest tumor/muscle ratios were found at 48 h post injection. Both AUC and relative ratio of the AUCs (RR-AUC) also showed that 6 mol% PEGylated liposomes significantly reduced the uptake of drugs in the reticuloendothelial system (RES), yet enhanced the uptake in the tumor. Gamma scintigraphy at 48 h post injection also demonstrated more distinct tumor uptake with 6 mol% PEG (111)In liposomes as compared to that of 0.9 mol% PEGylated liposomes (p0.01). BLI and in vivo tumor growth tracing showed that growth in tumor volume could largely be inhibited by 6 mol% PEG (111)In liposomes. The results suggest that 6 mol% PEGylated liposomes might be a more suitable liposomal carrier for drug delivery than 0.9 mol% PEGylated liposomes, not only by reducing the drug accumulation in the RES or its related organs, but by prolonging drug circulation and eventually enhancing the targeting efficiency in the tumor to reach a better therapeutic index.

Background In order to clarify the role of positron emission tomography–computed tomography (PET/CT) in thoracic esophageal squamous cell carcinoma we investigated its value in predicting locoregional invasion. Methods Forty-five patients receiving curative esophagectomy and lymph node dissection were included. The relationship between PET/CT findings and pathology results were studied. Correlation between nodal uptake and the modified lymph node staging, which is based on number of involved nodes (N0 = no nodes; N1=1 to 3 nodes; N2=more than 3 nodes), was evaluated. Results The mean maximal standardized uptake value (SUV max ) was 5.09 ± 4.00 in T1, 14.17 ± 2.46 in T2, 13.32 ± 3.96 in T3, and 10.37 ± 1.94 in T4 primary tumor. The SUV max was significantly lower in stage T1 tumors than in stage T2 and T3 tumors. For regional nodal involvement, PET/CT findings significantly correlated with pathology results. However, the sensitivity, specificity, and accuracy of PET/CT were only 57.1%, 83.3%, and 71.1%, respectively, and even lower for detecting nonregional lymph node metastasis. When stratified by the modified staging system, the mean SUV max was 0.64 ± 1.60 in N0, 1.43 ± 2.08 in N1, and 4.67 ± 4.32 in N2 regional lymph node metastases, and was significantly higher in patients with N2 metastasis than in patients with N0 and N1 metastases. Conclusions Locoregional invasion in esophageal cancer can be predicted by PET/CT. The SUV max of the primary tumor helped identify T1 tumor, and the SUV max of the regional lymph nodes correlated with the severity of nodal involvement.

The term input function usually refers to the tracer plasma time activity curve (pTAC), which is necessary for quantitative positron emission tomography (PET) studies. The purpose of this study was to acquire the pTAC from the independent component analysis (ICA) estimated whole blood time activity curve (wTAC) using our proposed method: FDG blood-cell-two-compartment model (BCM). We also compared published models, which are linear haematocrit (HCT) correction, nonlinear HCT correction, and two-exponential correction. According to the results, the normalized root mean square error (NRMSE) and error of area under curve (EAUC) of BCM estimated pTAC were the smallest. Compartmental and graphic analyses were used to estimate metabolic rate of FDG (MR FDG ). The percentage error of MR FDG (PE MRFDG ) estimated from BCM corrected pTAC was also the smallest. The BCM is a better choice to transfer wTAC to pTAC for quantification.