In vivo mesolimbic D2/3 receptor binding predicts posttherapeutic clinical responses in restless legs syndrome: a positron emission tomography study

Although D2/3 agonists have been used as a first-line medication for idiopathic restless legs syndrome (iRLS), findings on D2/3 receptors have been inconsistent. Here, we aimed to clarify the contribution of D2/3 receptor function to the clinical symptoms of iRLS by comparing the binding potential (BP_ND) of [¹¹C]raclopride with clinical improvements after D2/3 stimulation by pramipexole. Eight drug-naïve, iRLS patients and eight age-matched healthy subjects were scanned with positron emission tomography (PET). After PET scans, all patients received pramipexole (0.125 mg) orally for 2 weeks. Patients were evaluated every day with several standardized clinical tests. The BP_ND values were compared using regions of interest and voxel-based methods. Results showed that the mean magnitude of [¹¹C]raclopride BP_ND in the mesolimbic dopamine region (nucleus accumbens (NA) and caudate) was significantly lower in the iRLS group. No significant differences between groups were observed in the putamen. The NA [¹¹C]raclopride BP_ND levels correlated negatively with clinical severity scores and positively with the degree of posttreatment improvement in iRLS. The present results suggest that alterations in mesolimbic D2/3 receptor function reflect the pathophysiology of iRLS, and the baseline availability of D2/3 receptors may predict the clinical outcome after D2/3 agonist treatment.     

Intra-focal fixation for treating distal radius fracture: Results of 104 cases

Intra-focal fixation for a displaced distal radius fracture is a surgical option that achieves early functional recovery. We report a retrospective evaluation of the results with various types of distal radius fracture, using various fixation materials in 104 patients (69 women and 35 men; average age, 51.4 years; range, 4–91 years). Fracture types classified according to Frykman were: 14 type I, 15 type II, 6 type III, 16 type IV, 10 type V, 16 type VI, 9 type VII, and 18 type VIII. Fixation materials used were: conventional Kirschner wire in 6 patients, threaded Kirschner wire in 38, arum pins in 38, and conehead wedging screws in 22. The results for patients with Frykman types V–VIII fractures were not as good as those for patients with types I–IV. The arum pin and conehead wedging screw were each superior to either Kirschner wire or threaded Kirschner wire in reducing the fracture and in maintaining fixation. Our evaluation suggested that intra-focal fixation was also suitable for treatment of an intra-articular fracture. In elderly patients, we recommend the arum pin and conehead wedging screw as fixation materials, and suggest short-term postoperative immobilization. Received for publication on May 1, 1998; accepted on July 13, 1998     

The clinicopathologic features of serum CA 19-9-positive colorectal cancers

The preoperative serum levels of carbohydrate antigen 19-9 (CA 19-9) were determined in 206 patients with colorectal cancer, 52 (25.2%) of whom were found to be positive. All of these patients had advanced cancers and significantly higher incidences of tumor invasion through the muscularis propria (91.3%) and lymph node involvement (54.5%). The incidences of liver metastasis and Dukes' stage D in the CA 19-9-positive group were 38.5% and 42.9%, respectively, significantly higher than those in the CA 19-9-negative group of 6.5% and 14.8%, respectively. Moreover, the incidence of liver metastasis in the CA 19-9-positive group patients with Dukes' stage D cancer was 95.2% (20/21); CA 19-9 showing higher specificity (81.7%) and a more positive predictive value (38.5%) for liver metastasis than the carcinoembryonic antigen (CEA). When a cutoff value of 160 U/ml was used, the specificity and positive predictive value reached 97.7% and 81.0%, respectively. An analysis of response operating characteristic (ROC) curves for liver metastasis revealed that CA 19-9 was more useful than CEA. The long-term survival of the CA 19-9-positive group patients was significantly worse than that of the CA 19-9-negative group patients (P < 0.0001), with no 1.25-year survivors in the former group when the cutoff value of 160U/ml was used. These results suggest that serum CA 19-9 as a useful preoperative indicator of liver metastasis and prognosis in colorectal cancer.     

Imaging of gynecologic tumors: comparison of (11)C-choline PET with (18)F-FDG PET.

This study was designed to compare the value of PET using (11)C-choline with that of PET using (18)F-FDG for the diagnosis of gynecologic tumors. METHODS: We examined 21 patients, including 18 patients with untreated primary tumors and 3 patients with suspected recurrence of ovarian cancer. (11)C-choline PET and (18)F-FDG PET were performed within 2 wk of each other on each patient. The patients fasted for at least 5 h before the PET examinations, and PET was performed 5 min ((11)C-choline) and 60 min ((18)F-FDG) after injection of each tracer. PET images were corrected for the transmission data, and the reconstructed images were visually analyzed. Then, the standardized uptake value (SUV) was calculated for quantitative assessment of tumor uptake. PET results were compared with surgical histology or >6 mo of clinical observations. RESULTS: Of 18 untreated patients, (11)C-choline PET correctly detected primary tumors in 16 patients, whereas (18)F-FDG PET detected them in 14 patients. In 1 patient with small uterine cervical cancer and 1 diabetic patient with uterine corpus cancer, only (11)C-choline PET was true-positive. Both tracers were false-negative for atypical hyperplasia of the endometrium in 1 patient and were false-positive for pelvic inflammatory disease in 1 patient. For the diagnosis of recurrent ovarian cancer (n = 3), (11)C-choline PET and (18)F-FDG PET were true-positive in 1 patient, whereas neither tracer could detect cystic recurrent tumor and microscopic peritoneal disease in the other 2 patients. In the 15 patients with true-positive results for both tracers, tumor SUVs were significantly higher for (18)F-FDG than for (11)C-choline (9.14 +/- 3.78 vs. 4.61 +/- 1.61, P < 0.0001). In 2 patients with uterine cervical cancer, parailiac lymph node metastases were clearly visible on (18)F-FDG PET but were obscured by physiologic bowel uptake on (11)C-choline PET. CONCLUSION: The use of (11)C-choline PET is feasible for imaging of gynecologic tumors. Unlike (18)F-FDG PET, interpretation of the primary tumor on (11)C-choline PET is not hampered by urinary radioactivity; however, variable background activity in the intestine may interfere with the interpretation.     

Extrastriatal spreading of microglial activation in Parkinson’s disease: a positron emission tomography study

Background

The neuroinflammatory glial response contributes to the degenerative process in Parkinson’s disease (PD). However, the pattern of microglial progression remains unclear.

Methods

We evaluated microglial activation in early stage PD patients by quantifying changes in neuroinflammation using PET with [¹¹C]DPA713, a selective PET tracer for microglial activation. Eleven PD patients (Hoehn and Yahr stages 1–2) without dementia underwent the [¹¹C]DPA713 PET scan two times with 1 year apart. The binding potential (BP_ND) was estimated with the simplified reference tissue model. Voxelwise and regions of interest analyses were used to compare the regional BP_ND among groups.

Results

Significant increase in [¹¹C]DPA713 BP_ND was found extrastriatally in the occipital, temporal and parietal cortex in PD patients, and the degree of BP_ND became much higher over the brain regions predominantly in the temporal and occipital cortex 1 year later.

Conclusion

The current results indicated that an extrastriatal spreading of microglial activation reflects one of PD pathophysiology occurring at an early stage.

     

Neural substrates in judgment process while playing go: a comparison of amateurs with professionals

A professional go player shows incomparable ability in judgment during go game. Positron emission tomography (PET) was used to investigate the neural substrates of professional go player's judgment process. Eight professional go players and six amateur players were instructed to think over silently in the opening-stage game (fuseki, territorial planning) problems and the life-or-death (tsume, checkmate judgment) problems presented on the monitor in front of them for 60 s of H2 15O PET scans and to state the answer afterwards. We found that in the territorial planning problems the parietal activation was equally observed in both groups with the additional prefrontal activation in the amateur group, and in the checkmate-decision problems the precuneus and cerebellum were activated in professionals while the premotor and parietooccipital cortices (visuospatial processing region) were extensively activated in amateurs. The comparison of the two groups showed stronger activations in the precuneus and cerebellum in the professionals in contrast to the premotor activation in amateurs during checkmate judgment. In addition, the cerebellum was remarkably activated in the higher ranking professional players. These findings suggested the cerebellum and precuneus play important roles in processing of accurate judgment by visual imagery and nonmotor learning memory processes in professional go players.     

A case of non-curatively resected gastric cancer successfully treated over 17 months with TS-1 and irinotecan combination therapy

We report a case of non-curatively resected gastric cancer successfully treated with TS-1 and irinotecan (CPT-11) combination therapy, resulting in long-term survival of 17 months. A 56-year-old woman underwent noncurative resection with total gastrectomy for advanced gastric cancer with severe lymph node metastasis on June 3, 2004. Postoperatively, She received TS-1 and CPT-11 combination therapy (TS-1 80 mg/m(2) day 1-21, CPT-11 80 mg/m(2) day 1, 15, every 5 weeks). However, due to grade 4 neutropenia, and grade 3 nausea and anorexia in the first course, both doses were reduced. Since then, no grade 3 or severer adverse reactions have been observed. After 5 courses, partial response to lymph node metastasis was obtained, and her quality of life was improved. Thus, TS-1 and CPT-11 combination therapy has been effective for 17 months, suggesting that it is promising for long-term administration and survival to continue it perseveringly.     

Changes in cerebral blood flow under the prone condition with and without massage

To investigate changes in regional cerebral blood flow (rCBF) under the prone condition with and without light massage on the back, we measured rCBF quantitatively in healthy human subjects using positron emission tomography with H₂¹⁵O. Biochemical tests showed that the light massage (palm-pressure) reduced levels of stress-related serum cortisol and salivary stress protein chromogranin-A measured after the PET examination. Absolute rCBF significantly increased in the parietal cortex (precuneus) under the prone condition compared with the supine condition, and this rCBF increase was in parallel with comfortable sensation and slowing heart rate during the massage. Correlation analysis in statistical parametric mapping showed that the amygdalar and basal forebrain rCBF correlated with parasympathetic function (heart rate reduction), indicating involvement of the forebrain-amygdala system in mediating activities in the autonomic nervous system in the presence of comfortable sensation. To conclude, prone posture itself can stimulate the precuneus region to raise awareness, and the light massage on the back may help accommodate the brain to comfortable stimulation.     

Patients’ characteristics and outcomes depending on complete or incomplete unilateral spatial neglect

Unilateral spatial neglect (USN) is known to depress the activities of daily living. The purpose of this study was to clarify that categorizing the type of USN using line cancelation and line bisection tests is important when evaluating patients with acute intracerebral hemorrhage (ICH). In this study, patients with ICH were prospectively evaluated for the presence of USN using line cancelation and line bisection tests. They were classified into an incomplete USN group (iUSN = abnormal results in either test) or a complete USN group (cUSN = abnormal findings in both tests). We compared the initial severity of ICH and the outcomes of USN in the two groups. We were able to assess 16 patients, among whom 10 showed USN. Seven were then categorized as having iUSN and three as having cUSN. The median hematoma volume was larger in the cUSN group than in the iUSN group. The USN symptoms of patients in the iUSN group disappeared during the chronic phase, whereas the symptoms of patients in the cUSN group continued. The type of USN was associated with the initial severity of ICH and the persistence of USN.