Effects of pegfilgrastim on normal biodistribution of 18F-FDG: preclinical and clinical studies.

The purpose of this study was to evaluate the effects of pegfilgrastim, a long-acting granulocyte colony-stimulating factor, on the normal biodistribution of (18)F-FDG in an animal model and in humans. METHODS: Two groups of 12 rats received a single subcutaneous injection of either normal saline or pegfilgrastim. One, 7, 14, and 21 d after injection, biodistribution studies were performed 1 h after (18)F-FDG injection. Sixteen breast cancer patients underwent baseline (18)F-FDG PET/CT and, approximately 1 wk after receiving 1 dose of docetaxel and adjunctive pegfilgrastim, follow-up (18)F-FDG PET/CT (scan 2). Standardized uptake values corrected for lean body mass (SUL) were determined for several normal organs before and after therapy. RESULTS: In rats, bone marrow (18)F-FDG uptake (standardized uptake value) was higher in the pegfilgrastim group 1 d after injection (mean +/- SD, 8.3 +/- 4.1 vs. 2.5 +/- 0.2, P < 0.05), whereas (18)F-FDG uptake in blood was lower (0.41 +/- 0.06 vs. 0.49 +/- 0.01, P < 0.05). In patients, mean SUL was higher in bone marrow (4.49 +/- 1.50 vs. 1.33 +/- 0.22, P < 0.0001), spleen (3.29 +/- 0.83 vs. 1.23 +/- 0.23, P < 0.0001), and liver (1.45 +/- 0.25 vs. 1.31 +/- 0.23, P = 0.01) but lower in brain (4.18 +/- 0.76 vs. 5.14 +/- 1.44, P < 0.01) on scan 2 than on the baseline scan. CONCLUSION: In both the animal model and humans, pegfilgrastim markedly increased bone marrow uptake of (18)F-FDG and reduced (18)F-FDG uptake in some normal tissues. These profound alterations in (18)F-FDG biodistribution induced by pegfilgrastim must be considered when one is evaluating quantitative (18)F-FDG PET scans for tumor response to therapy.     

Virtual endoscopic images by 3D FASE cisternography for neurovascular compression.

Three-dimensional fast asymmetric spin echo (3D FASE) cisternography provides high spatial resolution and excellent contrast as a water image acquisition technique. It is also useful for the evaluation of various anatomical regions. This study investigated the usefulness and limitations of virtual endoscopic images obtained by 3D FASE MR cisternography in the preoperative evaluation of patients with neurovascular compression. The study included 12 patients with neurovascular compression: 10 with hemifacial spasm and two with trigeminal neuralgia. The diagnosis was surgically confirmed in all patients. The virtual endoscopic images obtained were judged to be of acceptable quality for interpretation in all cases. The areas of compression identified in preoperative diagnosis with virtual endoscopic images showed good agreement with those observed from surgery, except in one case in which the common trunk of the anterior inferior cerebellar artery and posterior inferior cerebellar artery (AICA-PICA) bifurcated near the root exit zone of the facial nerve. The veins are displayed in some cases but not in others. The main advantage of generating virtual endoscopic images is that such images can be used for surgical simulation, allowing the neurosurgeon to perform surgical procedures with greater confidence.     

Preoperative identification of subthalamic nucleus for deep brain stimulation using three-dimensional phase sensitive inversion recovery technique.

PURPOSE: We assessed the feasibility of utilizing three-dimensional (3D) phase sensitive inversion recovery (IR) images for preoperatively determining deep brain stimulator position. METHODS: We measured geometric distortion with a grid phantom and evaluated images of 3 volunteers to determine optimum imaging parameters for 3D phase sensitive IR. RESULTS: Geometric distortion measured less than 1.0%. Respective inversion and recovery times, which provided high T(1) contrast between the subthalamic nucleus and adjacent tissue, were 200 and 4000 ms. In studies of 3 volunteers and 2 patients, the subthalamic nucleus was clearly depicted in 3D phase sensitive IR images. The measured coordinates of the subthalamic nucleus agreed well with those calculated by conventional estimation from midpoint of the anterior and posterior commissure. CONCLUSION: Three-dimensional phase sensitive inversion recovery was useful in visualizing the subthalamic nucleus for effective deep brain stimulation.     

Whole genome association study of rheumatoid arthritis using 27 039 microsatellites

A major goal of current human genome-wide studies is to identify the genetic basis of complex disorders. However, the availability of an unbiased, reliable, cost efficient and comprehensive methodology to analyze the entire genome for complex disease association is still largely lacking or problematic. Therefore, we have developed a practical and efficient strategy for whole genome association studies of complex diseases by charting the human genome at 100 kb intervals using a collection of 27,039 microsatellites and the DNA pooling method in three successive genomic screens of independent case-control populations. The final step in our methodology consists of fine mapping of the candidate susceptible DNA regions by single nucleotide polymorphisms (SNPs) analysis. This approach was validated upon application to rheumatoid arthritis, a destructive joint disease affecting up to 1% of the population. A total of 47 candidate regions were identified. The top seven loci, withstanding the most stringent statistical tests, were dissected down to individual genes and/or SNPs on four chromosomes, including the previously known 6p21.3-encoded Major Histocompatibility Complex gene, HLA-DRB1. Hence, microsatellite-based genome-wide association analysis complemented by end stage SNP typing provides a new tool for genetic dissection of multifactorial pathologies including common diseases.     

Molecular and immunological approach to hematological disease: detection and analysis of intracellular modified nucleosides by flow cytometry

Modified nucleosides are components of ribosomal RNA (rRNA), transfer RNA (tRNA) and messenger RNA (mRNA). 1-methyladenosine and pseudouridine are members of those modified nucleosides. The urinary concentration of 1-methyladenosine and pseudouridine of cancer patients are higher than that of healthy controls, and those compounds were reduced after effective chemotherapy. Thus those compounds might be expected to use as tumor markers. In this study cellular origin of 1-methyladenosine and pseudouridine were analysed about two tumor cell lines (HUT-102, THP-1), peripheral blood lymphocytes (PBL) from healthy adult and PBL under the phytohemagglutinin stimulation, by flow cytometric analysis and immunofluorescent staining of cellular RNA using monoclonal antibodies specific for 1-methyladenosine (AMA) and pseudouridine (APU). Both 1-methyladenosine and pseudouridine were detected in more than 90% of tumor cells above the thresholds of flow cytometric detection (Spectrum III, Ortho). The PBL under the PHA stimulation also tended to take the same way of the tumor cell lines, whereas few of the PBL contained 1-methyladenosine above the thresholds. According to the DNA analysis of those cell lines, high contents of the modified nucleosides in the cell might follow DNA synthesis, this leads to one reason for high levels of the urinary excretion of the modified nucleosides in cancer patient.     

Solute removal characteristics of continuous recirculating peritoneal dialysis in experimental and clinical studies

Continuous recirculating peritoneal dialysis (CRPD) was introduced to enhance solute removal efficiency in conventional peritoneal dialysis (PD) therapies such as continuous ambulatory peritoneal dialysis (CAPD). In CRPD, a portion of the dwell dialysate in the patient's peritoneal cavity is drained through a double-lumen catheter and purified by an extracorporeal dialyzer. In this study, solute removal characteristics and safety of CRPD are examined in ex vivo and clinical studies. Recirculation dialysis experiments using nine dogs (13.6 +/- 2.5 kg of body weight) were carried out for 240 min in the ex vivo study, whereas another seven dogs (12.1 +/- 2.8 kg) received conventional peritoneal dialysis (CPD) (120 min dwelling x 2) and six additional dogs (11.9 +/- 2.7 kg) received a Tidal PD (20 min dwelling x 12; 50% of tidal volume ratio) as controls. The ex vivo study revealed that CRPD has a higher efficiency for solute removal than CPD and is equivalent to Tidal PD. In the BUN reduction rate, the 19.4 +/- 5.5% in 240 min CRPD (n = 9) was significantly higher (p < 0.05) than the 3.5 +/- 3.6% in 240 min CPD (n = 7) and equivalent to the 17.3 +/- 4.7% in 240 min Tidal PD (n = 6). Continuous recirculating peritoneal dialysis maintained a low UN level in the peritoneal cavity due to dialysis with an extracorporeal dialyzer. This tendency was also seen in creatinine removal. In the clinical study, CRPD (n = 10) and CPD (n = 5) treatments were used in three renal failure patients. Higher solute removal efficiency was shown in CRPD than in CPD treatments, and the urea peritoneal clearance was 14.1 +/- 4.4 ml/min in CRPD (n = 10), significantly higher (p < 0.05) than the 7.3 +/- 2.1 ml/min in CPD (n = 5). No fibrin formation occurred during CRPD treatments.     

Modified load sharing rip-stop technique in patients with traumatic transtendinous rotator cuff tear: Surgical technique and clinical outcomes

BackgroundTranstendinous rotator cuff tear is likely to occur due to trauma in sports activities, with a frequency of <2% of total rotator cuff tears. These tears are difficult to treat because of limited tendon tissue in the proximal stump, and standard repair techniques are sometimes ineffective. Few studies have reported on the repair technique and clinical outcomes for transtendinous rotator cuff tear, and an appropriate repair technique has, therefore, not been established. The purpose of this study was to use our modified load sharing rip-stop technique to repair transtendinous rotator cuff tear and to clarify the clinical effectiveness of this technique.MethodsThis was a retrospective case series review of eight patients who underwent the modified load sharing rip-stop technique for repairing traumatic transtendinous rotator cuff tear between January 2013 and June 2017. The eight patients were followed up for at least 2 years (range: 24–41 months). Cuff integrity was evaluated using magnetic resonance imaging at 12 months after surgery using the Sugaya classification. We evaluated the pre- and postoperative ranges of motion, American Shoulder and Elbow Surgeons score, Constant Shoulder Score, and muscle strength at 90° abduction. Data were analyzed using the Mann–Whitney U test and Fisher's exact tests. P < .05 was considered to indicate statistical significance.ResultsSix patients were classified as Sugaya I and two as Sugaya II. ASES score (38.5–90.2, P = .0008), Constant shoulder score (36.5–79, P = .002), flexion (85°–158.1°, P = .002), abduction (85°–157.5°, P = .001), external rotation (38.8°–55°, P = .024), and muscle strength at 90° abduction (2.95–5.39 kg, P = .028) improved significantly. Six patients were able to return to their previous sports activity.ConclusionUsing our modified load sharing rip-stop technique for repair of transtendinous rotator cuff tear, patients obtained good clinical outcomes and could return to sports activities.     

Thyroid hemiagenesis with postpartum silent thyroiditis

A 28-year-old woman with thyroid hemiagenesis, who had been diagnosed as having Graves' disease, became pregnant during the course of methimazole treatment. The treatment was terminated in the second trimester. She delivered a normal infant at full term. She became thyrotoxic 3 months after the delivery, hypothyroid 6 months after the delivery, and finally euthyroid 11 months after the delivery without undergoing any treatment. This clinical course indicates that she developed silent thyroiditis after the delivery. A diagnosis of thyroid hemiagenesis was made on the basis of ultrasonography of the thyroid and 99mTc-pertechnetate thyroid scintiscan.