Transport of cis- and trans-4-[(18)F]fluoro-L-proline in F98 glioma cells

The transport mechanisms of cis-4-[(18)F]fluoro-L-proline (cis-FPro) and trans-4-[(18)F]fluoro-L-proline (trans-FPro) were studied in F98 rat glioma cells in comparison to the natural parent [(3)H]-L-proline. Uptake rates of cis-FPro and trans-FPro in F98 glioma cells were 50-70% lower than those of [(3)H]-L-proline. The amino transport system A inhibitor MeAIB reduced the uptake of [(3)H]-L-proline by 30% and uptake of cis-FPro by 46% while uptake of trans-FPro was not significantly changed. BCH inhibited the uptake of all tracers by 35-44%, serine by 70-90% and L-proline by 60 -80%. Absence of Na(+) reduced uptake of all tracers significantly but no further inhibitory effect could be observed which suggests a component of unspecific uptake. Radioactivity of cis- and trans-FPro in the acid precipitable fraction was < 1% after 120 min incubation time while [(3)H]-L-proline exhibited a 20% incorporation into protein. Whole body PET scans in humans demonstrated a retention of cis-FPro in the renal cortex, liver and the pancreas while trans-FPro was retained particularly in muscles. We conclude that system A amino acid transport appears to be selectively relevant for cis-FPro which may contribute to the observed differences in whole body distribution of cis-FPro and trans-FPro in humans.     

Gamma camera dual imaging with a somatostatin receptor and thymidine kinase after gene transfer with a bicistronic adenovirus in mice

PURPOSE: To compare two systems for assessing gene transfer to cancer cells and xenograft tumors with noninvasive gamma camera imaging. MATERIALS AND METHODS: A replication-incompetent adenovirus encoding the human type 2 somatostatin receptor (hSSTr2) and the herpes simplex virus thymidine kinase (TK) enzyme (Ad-hSSTr2-TK) was constructed. A-427 human lung cancer cells were infected in vitro and mixed with uninfected cells at different ratios. A-427 tumors in nude mice (n = 23) were injected with 1 x 10(6) to 5 x 10(8) plaque-forming units (pfu) of Ad-hSSTr2-TK. The expressed hSSTr2 and TK proteins were imaged owing to internally bound, or trapped, technetium 99m ((99m)Tc)-labeled hSSTr2-binding peptide (P2045) and radioiodinated 2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl-5-iodouracil (FIAU), respectively. Iodine 125 ((125)I)-labeled FIAU was used in vitro and iodine 131 ((131)I)-labeled FIAU, in vivo. The (99m)Tc-labeled P2045 and (125)I- or (131)I-labeled FIAU were imaged simultaneously with different window settings with an Anger gamma camera. Treatment effects were tested with analysis of variance. RESULTS: Infected cells in culture trapped (125)I-labeled FIAU and (99m)Tc-labeled P2045; uptake correlated with the percentage of Ad-hSSTr2-TK-positive cells. For 100% of infected cells, 24% +/- 0.4 (mean +/- SD) of the added (99m)Tc-labeled P2045 was trapped, which is significantly lower (P <.05) than the 40% +/- 2 of (125)I-labeled FIAU that was trapped. For the highest Ad-hSSTr2-TK tumor dose (5 x 10(8) pfu), the uptake of (99m)Tc-labeled P2045 was 11.1% +/- 2.9 of injected dose per gram of tumor (thereafter, dose per gram), significantly higher (P <.05) than the uptake of (131)I-labeled FIAU at 1.6% +/- 0.4 dose per gram. (99m)Tc-labeled P2045 imaging consistently depicted hSSTr2 gene transfer in tumors at all adenovirus doses. Tumor uptake of (99m)Tc-labeled P2045 positively correlated with Ad-hSSTr2-TK dose; (131)I-labeled FIAU tumor uptake did not correlate with vector dose. CONCLUSION: The hSSTr2 and TK proteins were simultaneously imaged following dual gene transfer with an adenovirus vector.     

High-level language ability in healthy individuals and its relationship with verbal working memory

The aims of the study were to investigate healthy subjects’ performance on a clinical test of high-level language (HLL) and how it is related to demographic characteristics and verbal working memory (VWM). One hundred healthy subjects (20–79 years old) were assessed with the Swedish BeSS test (Laakso, Brunnegård, Hartelius, & Ahlsén, 2000) and two digit span tasks. Relationships between the demographic variables, VWM and BeSS were investigated both with bivariate correlations and multiple regression analysis. The results present the norms for BeSS. The correlations and multiple regression analysis show that demographic variables had limited influence on test performance. Measures of VWM were moderately related to total BeSS score and weakly to moderately correlated with five of the seven subtests. To conclude, education has an influence on the test as a whole but measures of VWM stood out as the most robust predictor of HLL.     

Isotopic renal function studies in severe hypothyroidism and after thyroid hormone replacement therapy

AIM: To investigate the possible changes in the renal tubular function in severe short-term hypothyroidism using (99m)Tc-MAG(3) renography. METHODS: 27 consecutive thyroidectomized patients (7 males and 20 females) aged 19-79 (mean 53) years were included in the present study. (99m)Tc-MAG(3) renography was performed in all patients before and after thyroid hormone replacement therapy. In addition, (51)Cr-EDTA clearance and serum creatinine concentrations were determined. RESULTS: The serum creatinine concentrations were significantly increased in hypothyroidism as compared with the concentrations after thyroxine substitution (1.30 +/- 0.44 vs. 1.04 +/- 0.32 mg/dl, p < 0.05). According to the (51)Cr-EDTA clearance, the glomerular filtration rate was significantly lower in hypothyroidism than after treatment (61 +/- 18 vs. 75 +/- 23 ml/min). In contrast, we did not find any significant change in the renographic parameters for (99m)Tc-MAG(3) before and after treatment (total excreted activity 20 min after administration 51 +/- 12 vs. 54 +/- 14%; T(max) left:right 4.2 +/- 1.77 : 3.91 +/- 1.06 min vs. 4.1 +/- 1.66 : 4.4 +/- 1.96 min). CONCLUSIONS: We did not find any influence of thyroid hormones on the outcome of (99m )Tc-MAG(3) renography. As (99m)Tc-MAG(3) reflects the tubular function, it seems that the renal hemodynamic changes in severe hypothyroidism mainly affect the glomerular function. In general, the glomerular filtration rate reduction seems to be reversible after hormone substitution therapy; however, care has to be taken in patients with renal insufficiency.     

"Opioid creep" is real and may be the cause of "fluid creep"

Recent studies have shown that burn patients receive larger volumes of fluids than predicted by the Baxter formula and the reason for this is unclear. One potential reason is that increased analgesics are used which could blunt the response to fluid resuscitation. The purpose of this study was to compare the administration of opioid agonists in patients treated at a single burn center in the 1970s and in the year 2000. We performed a retrospective chart review comparing two matched cohorts. Group I consisted of 11 patients admitted between 1975 and 1978. Group II consisted of 11 patients admitted in 2000 matched for age, sex and %TBSA. Patients in Group II received a significantly higher mean opioid equivalent than those in Group I (26.5 +/- 12.3 versus 3.9 +/- 2.2 in the first 24h, P < 0.001). In addition, in Group II, a larger variety and combination of opioid agonists were used. This review demonstrates a significant increase from the 1970s to 2000 in the type, dose prescribed and dose delivered of opioid agonists. Along with "fluid creep", we have also increased our use of opioid agonists or "opioid creep". Higher doses of opioid agonists may have hemodynamic consequences, which may contribute to the increased fluid volumes.     

Long term effect of vagus nerve stimulation in pediatric intractable epilepsy: an extended follow-up

Purpose

Over the past two decades, vagus nerve stimulation (VNS) has become an accepted and viable treatment modality for intractable epilepsy both in children and adults. Earlier studies have demonstrated short-term seizure outcomes, usually for up to 5 years; so far, none have reported an extended outcome in children. We aimed to assess long term seizure outcome in children with intractable epilepsy for more than 5 years.

Methods

We identified patients who had VNS implantation for treatment of intractable epilepsy from March 2000 to March 2015 at our Epilepsy Center and collected data including demographic, age at epilepsy onset and VNS implantation, duration of epilepsy, seizure type, number of antiepilepsy drugs (AEDs), and monthly seizure frequency before VNS implantation and at the last clinic visit. Phone surveys were conducted with patients without recent clinic follow-up.

Results

Fifty-six patients (aged 4–17 at the time of implant) are the subjects of the study. Seizure reduction of >50 % was achieved in 9.8 % (6th month), 24 % (2nd year), 46.4 % (3rd year), and 54 %(5th year), and overall 35 (62.5 %) of the 56 subjects had a greater than 50 % reduction in seizure frequency at the last follow-up. Eleven patients became seizure free. The results, once obtained, were maintained steadily or even improved over time without any loss of efficacy during the follow-up. The only parameter, significantly related with clinical response, was age at seizure onset. The most frequent adverse events were hoarseness, cough, sore throat, and anorexia, experienced by 13 patients. Two patients had local wound infections and lead to the removal of the stimulator. An improvement in alertness, attention, and psychomotor activity, independent of the efficacy of vagal nerve stimulation, was observed in 8 patients.

Conclusion

To our knowledge, this is the first pediatric study evaluating seizure outcome over more than 5 years of follow-up, and demonstrates a favorable seizure outcome of >50 % seizure frequency in 62.5 % of patients and seizure freedom in 11 patients. It is well tolerated over an extended period of time.

     

Transvaginal cholecystectomy versus single-incision laparoscopic cholecystectomy versus four-port laparoscopic cholecystectomy: a prospective cohort study

Objective

This report describes the first prospective cohort study comparing transvaginal cholecystectomies (TVC) with single incision laparoscopic cholecystectomies (SILC) and four-port laparoscopic cholecystectomies (4PLC).

Methods

Between May 2009 and August 2010, 14 patients underwent a TVC. These patients were compared with patients who underwent SILC (22 patients) or 4PLC (11 patients) in a concurrent, randomized, controlled trial. Demographic data, operative time, numerical pain scales, complications, and return to work were recorded.

Results

Mean age (TVC: 33.5?±?3.0?year; SILC: 38.4?±?3.3?year; 4PLC: 35.5?±?4.1?year; p?=?0.58) and mean BMI (TVC: 28.8?±?1.5?kg/m²; SILC: 31.8?±?1?kg/m²; 4PLC: 31.4?±?2.2?kg/m²; p?=?0.35) were not statistically significant. However, mean operative time (TVC: 67?±?3.9?min; SILC: 48.9?±?2.6?min; 4PLC: 42.3?±?3.9?min; p?p?=?0.02) with equilibration of pain scores by days 14 and 30. Return to work (TVC: 6.4?±?1.5?days; SILC: 13.1?±?1.3?days; 4PLC: 14.1?±?1.4?days; p?Conclusions Transvaginal cholecystectomy is a safe and well-tolerated procedure with statistically significantly less pain at 1 and 3?days after surgery, with a faster return to work but longer operative times compared with single incision and four-port laparoscopic cholecystectomy.     

Designing the selenium and bladder cancer trial (SELEBLAT), a phase lll randomized chemoprevention study with selenium on recurrence of bladder cancer in Belgium

Background

Growing evidence indicates that oxidative stress can be a primary cause of male infertility. Non-enzymatic antioxidants play an important protective role against oxidative damages and lipid peroxidation. Human seminal plasma is a natural reservoir of antioxidants. The aim of this study was to determine glutathione (GSH) concentrations, trace element levels (zinc and selenium) and the lipid peroxidation end product, malondialdehyde (MDA), in the seminal plasma of men with different fertility potentials.

Methods

Semen samples from 60 fertile men (normozoospermics) and 190 infertile patients (74 asthenozoospermics, 56 oligozoospermics, and 60 teratozoospermics) were analyzed for physical and biochemical parameters. Zinc (Zn) and selenium (Se) levels were estimated by atomic absorption spectrophotometry. Total GSH (GSHt), oxidized GSH (GSSG), reduced GSH (GSHr) and MDA concentrations were measured spectrophotometrically.

Results

Zn and Se concentrations in seminal plasma of normozoospermics were more elevated than the three abnormal groups. Nevertheless, only the Zn showed significant differences. On the other hand, Zn showed positive and significant correlations with sperm motility (P = 0.03, r = 0.29) and count (P < 0.01, r = 0.49); however Se was significantly correlated only with sperm motility (P < 0.01, r = 0.36). GSHt, GSSG and GSHr were significantly higher in normozoospermics than in abnormal groups. We noted a significant association between seminal GSHt and sperm motility (P = 0.03). GSSG was highly correlated to sperm motility (P < 0.001) and negatively associated to abnormal morphology (P < 0.001). GSHr was significantly associated to total sperm motility (P < 0.001) and sperm count (P = 0.01). MDA levels were significantly higher in the three abnormal groups than in normozoospermics. Rates of seminal MDA were negatively associated to sperm motility (P < 0.01; r = -0.24) and sperm concentration (P = 0.003; r = -0.35) Meanwhile, there is a positive correlation between seminal lipid peroxidation and the percentage of abnormal morphology (P = 0.008).

Conclusions

This report revealed that decreased seminal GSH and trace element deficiencies are implicated in low sperm quality and may be an important indirect biomarker of idiopathic male infertility. Our results sustain that the evaluation of seminal antioxidant status in infertile men is necessary and can be helpful in fertility assessment from early stages.