Diagnosis of pheochromocytoma using [123I]- compared with [131I]-metaiodobenzylguanidine scintigraphy

BACKGROUND: Patient with pheochromocytoma (PCT) cannot be cured without operation, therefore, preoperative determination of the localization of PCT should be performed accurately. [131I]-Metaiodobenzylguanidine (MIBG) scintigraphy is a gold standard for the diagnosis of PCT. However, [123I]-MIBG is also found to accumulate in PCT. In order to clarify the usefulness of [123I]-MIBG scintigraphy for the local detection of PCT, we compared the distribution of [123I]- and [131I]-MIBG in patients with or without PCT. METHODS: [131I]- and [123I]-MIBG scintigraphy was performed in 29 and 16 patients, respectively. In the former group, 14 patients had PCT, 12 had hypertension without any adrenal disorder and three had other diseases. In the latter group, eight patients had PCT, two had hypertension without any adrenal disorder and six had other diseases. The sensitivity, specificity and accuracy of [123I]-compared with [131I]-MIBG scintigraphy were compared. RESULTS: The sensitivity of [131I]- and [123I]-MIBG scintigraphy was 85.7 and 90%, respectively. The specificity of each test was 100%. The accuracy of [131I]- and [123I]-MIBG scintigraphy was 93.1 and 95%, respectively. The quality of images obtained using [123I]-MIBG was better than with [131I]-MIBG, because [123I]-MIBG generated a higher dose of gamma-rays with a higher specificity than [131I]-MIBG. In addition, normal adrenal grands were visualized in 50% of patients tested with [123I]-MIBG scintigraphy. CONCLUSIONS: These results indicate that [123I]-MIBG scintigraphy is a valuable tool for the local detection of PCT, as is [131I]-MIBG scintigraphy. Furthermore, it is possible that [123I]-MIBG can be used as an alternative to [131I]-MIBG for the detection of PCT. Our study was not a prospective study and the background of the patients was not matched. Further prospective studies are needed in order to determine the efficacy of [123I]-MIBG scintigraphy for the diagnosis of PCT.     

Coordination and symmetry patterns during the drop vertical jump, 6‐months after first‐time lateral ankle sprain

To evaluate the adaptive movement and motor control patterns of a group with a 6‐month history of first‐time lateral ankle sprain (LAS) injury during a drop vertical jump (DVJ) task. Fifty‐one participants with a 6‐month history of first‐time acute LAS injury and twenty controls performed a DVJ task. 3D kinematic and sagittal plane kinetic profiles were plotted for the lower extremity joints of both limbs for the drop jump (phase 1) and drop landing (phase 2) phases of the DVJ. Inter‐limb symmetry and the rate of impact modulation (RIM) relative to bodyweight (BW) during both phases of the DVJ were also determined. LAS participants displayed bilateral increases in knee flexion and an increase in ankle inversion during phases 1 and 2, respectively. They also displayed reduced ankle plantar flexion on their injured limb during both phases of the DVJ (p < 0.05); increased inter‐limb asymmetry of RIM was noted for both phases of the DVJ, while the moment‐of‐force profile exhibited bilaterally greater hip extensor dominance during phase 1. Participants with a 6‐month history of first‐time LAS display some movement patterns consistent with those observed in chronic ankle instability populations during similar tasks. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1537–1544, 2015.     

[18F]‐fluorocholine positron‐emission/computed tomography for lymph node staging of patients with prostate cancer: preliminary results of a prospective study

Study Type – Diagnostic (case series)
Level of Evidence 4

OBJECTIVES

To evaluate prospectively [¹⁸F]‐fluorocholine positron‐emission/computed tomography (FCH PET/CT) for lymph node staging of prostate cancer before intended curative therapy, and to determine whether imaging 15 or 60 min after radiotracer injection is preferable.

PATIENTS AND METHODS

In all, 25 consecutive patients with newly diagnosed prostate cancer (Gleason score >6, and/or a prostate‐specific antigen level of >10 ng/mL, and/or T3 cancer) were scanned before lymphadenectomy. Each patient was assessed twice with imaging, at 15 and 60 min after the injection with FCH. Images were compared with the results of histopathological examination of the surgically removed lymph nodes. Maximum standardized uptake values (SUV_max) at 15 and 60 min were also compared.

RESULTS

Histopathologically, metastases were present in removed lymph nodes from three patients. FCH PET/CT showed a high radiotracer uptake in four patients, the former three and a fourth. The sensitivity, specificity, positive and negative predictive value of FCH PET/CT for patient based lymph node staging of prostate cancer were 100%, 95%, 75% and 100%, respectively; the corresponding 95% confidence intervals were 29.2–100%, 77.2–99.9%, 19.4–99.4% and 83.9–100%, respectively. Values of SUV_max at early and late imaging were not significantly different.

CONCLUSIONS

This small series supports the use of FCH PET/CT as a tool for lymph node staging of patients with prostate cancer. Values of SUV_max at early and late imaging did not differ. However, larger prospective studies are needed to validate these findings.     

Whole-Body [18F]FDG PET in the Management of Metastatic Brain Tumours

Summary Background To determine its roles in the diagnosis and the systemic evaluation of metastatic brain tumours, whole-body positron emission tomography (PET) using [¹⁸F]FDG was performed in 20 consecutive patients. Methods  All patients were thought to be suffering or needing to be differentiated from metastatic brain tumours. Nine patients had multiple brain lesions; six were older and showed a rim-enhancing lesion with surrounding oedema; seven had homogeneously enhancing periventricular lesion(s) on computed tomography (CT) and/or magnetic resonance (MR) imaging, thought to be central nervous system lymphomas. Two patients had skull mass(es) and two patients had a solid mass suspected to be, respectively, a haemorrhagic metastasis and a metastatic malignant melanoma. All of them received whole-body [¹⁸F]FDG PET and conventional systemic work-up for metastasis in order to compare the results of the two methods. Results  Metastatic brain tumours were diagnosed on whole-body [¹⁸F]FDG PET in eleven patients who had extracranial and intracranial hypermetabolic lesions. In nine of these, a conventional work-up also detected primary lesions which on whole-body [¹⁸F]FDG PET were seen to be hypermetabolic foci. Systemic lymph node metastases were detected by whole-body [¹⁸F]FDG PET only in two patients and histological diagnosis was possible by biopsy of lymph nodes rather than of brain lesions. In the remaining nine patients who had only intracranial hypermetabolic foci, histological diagnosis was made by craniotomy or stereotactic biopsy. It was confirmed that seven of nine patients were suffering from a primary brain tumour and two from metastatic carcinoma. None of the nine showed evidence of systemic cancer on conventional work-up. Histological diagnoses of the primary brain tumours were four cases of primary central nervous system lymphoma and one each of multifocal glioblastoma, Ewing's sarcoma, and cavernous angioma.  Patients felt no discomfort during the whole-body [¹⁸F]FDG PET procedure and there were no complications. The false negative rate in [¹⁸F]FDG PET and in conventional work-up was 15.4% and 30.7% respectively. There were no false positives on either [¹⁸F]FDG PET or conventional work-up. Conclusion  It is suggested that whole-body [¹⁸F]FDG PET is a safe, reliable, and convenient method for the diagnosis and systemic evaluation of patients thought to be suffering or needing to be differentiated from a metastatic brain tumour.     

锝[99Tc]亚甲基双膦酸盐治疗骨质疏松症的研究进展

骨质疏松症是一种全身性代谢性骨骼疾病, 临床主要表现为骨骼疼痛、骨密度降低和骨折危险性增加，严重影响患者的生活质量。现阶段我国老年人中骨质疏松患病比例超过50% 以上，其中骨折发生率接近1/3。双膦酸盐是目前治疗骨质疏松的主要药物之一，因其具有强有力的破骨细胞抑制作用，临床应用广泛，而锝（99 Tc）亚甲基双膦酸盐( technetium methylenediphosphonate，99Tc-MDP) 注射液，商品名云克，是我国自主研制成功的新药，其主要成分是锝经氯化亚锡还原后与亚甲基双膦酸盐形成的螯合物，具有清除人体自由基、保护超氧化物歧化酶活力、抑制病理复化物的产生、抑制白细胞游走、降低胶原酶对软骨组织的破坏并修复破骨作用。可抑制骨吸收、改善骨质量、提高各个部位的骨密度、减低骨折风险，促进成骨，缓解骨痛。近年来已广泛应用于骨质疏松症的治疗，并已取得了较好的效果，且使用安全，无明显的副作用。本文对近年来云克应用于骨质疏松症的动物实验、临床疗效及安全性研究进行综述。     

Comparison of growth-induced resorption and denervation-induced resorption on the release of [3H]tetracycline, 45calcium, and [3H]collagen from whole bones of growing rats

The major effect of immobilization during growth is a smaller bone mass induced by either an increased bone resorption or a decreased bone formation. Using a method of analyzing radioisotopic loss of [3H]tetracycline and [3H]collagen from bone prelabeled in vivo, we compared the amount of bone resorption due to immobilization with bone resorption induced by growth. One hind limb was denervated in growing male rats, 6 weeks of age, that had been chronically prelabeled with [3H]tetracycline, 45calcium, and [3H]proline. The total radioactivity of the whole femur and tibia/fibula from the denervated limb was compared with that from bones of the control limb at 0, 1, 2, 4, and 8 weeks after denervation. The effect of growth on bone formation was measured by net increases in bone length, volume, and mass of matrix and mineral. Experimental bones had a significantly smaller volume and mass. Bone resorption was much greater during growth modeling than during denervation. The additional bone resorption induced by denervation was a small fraction (one-fourth) of the resorption induced by growth. Denervation during growth resulted in less bone being formed due to a smaller gain in matrix and mineral mass as a result of a reduction in bone formation.     

“Inside‐Out” PEGylation of Bovine β‐Cross‐Linked Hemoglobin

The development of a blood substitute is urgent due to blood shortages and potential communicable diseases. A novel method, inside‐out PEGylation, has been used here to conjugate a multiarm maleimide‐PEG (Mal‐PEG) to β‐cross‐linked (βXL‐Hb) hemoglobin (Hb) tetramers through the Cys β93 residues. This method produces a polymer with a single PEG backbone that is surrounded by multiple proteins, rather than coating a single protein with multiple PEG chains. Electrophoresis under denaturing conditions showed a large molecular weight species. Gel filtration chromatography and analytical ultracentrifugation determined the most prevalent species had three βXL‐Hb to one Mal‐PEG. Thermal denaturation studies showed that the cross‐linked and PEGylated species were more stable than native Hb. Cross‐linking under oxy‐conditions produced a high oxygen affinity Hb species (P₅₀ = 9.18 Torr), but the oxygen affinity was not significantly altered by PEGylation (P₅₀ = 9.67 Torr). Inside‐out PEGylation can be used to produce a hemoglobin‐based oxygen carrier and potentially for other multiprotein complexes.     

The usefulness of [131I]-metaiodobenzylguanidine ([131I]-MIBG) scintigraphy performed one week after administration in diagnosing pheochromocytoma

BACKGROUND: Imaging performed 36-48 h after metaiodobenzylguanidine (MIBG) injection is being widely used in the diagnosis of pheochromocytoma. However, there are some difficult cases to diagnose due to a high concentration of MIBG remaining in the background. We studied the significance of scans on the 7th day after MIBG injection when the concentration of MIBG in the background has declined. METHODS: Imaging was carried out on 11 cases before operation, five cases (eight times) after operation and 12 cases which had been strongly suspected of being pheochromocytoma, but later proved to be non-pheochromocytoma. RESULTS: In all the cases of pheochromocytoma, except one, the tumor imaging was clear 24-72 h after MIBG injection. As for the images after operation and those of the 12 non-pheochromocytoma cases, the scintigram made on the 7th day proved the negative pheochromocytoma. CONCLUSION: This approach was very effective not only for finding early small pheochromocytomas and the remnants of tumors after resection, but also in diagnosing non-pheochromocytoma.     

Anti‐gal antibodies in α1,3‐galactosyltransferase gene‐knockout pigs

Fang J, Walters A, Hara H, Long C, Yeh P, Ayares D, Cooper DKC, Bianchi J. Anti‐gal antibodies in α1,3‐galactosyltransferase gene‐knockout pigs. Xenotransplantation 2012; 19: 305–310. © 2012 John Wiley & Sons A/S. Abstract Serum anti‐galactose‐α1,3‐galactose (Gal) IgM and IgG antibody levels were measured by ELISA in α1,3‐galactosyltransferase gene‐knockout (GTKO) pigs (78 estimations in 47 pigs). A low level of anti‐Gal IgM was present soon after birth, and rose to a peak at 4–6 m, which was maintained thereafter even in the oldest pigs tested (at >2 yr). Anti‐Gal IgG was also present at birth, peaked at 3 m, and after 6 m steadily decreased until almost undetectable at 20 m. No differences in this pattern were seen between pigs of different gender. Total IgM followed a similar pattern as anti‐Gal IgM, but total IgG did not decrease after 6m. The data provide useful baseline data for future experimental studies in GTKO pigs, e.g., relating to the antibody response to WT pig allografts.     

Evaluation of Hyphecan (1‐4,2‐acetamide‐deoxy‐B‐D‐glucan polymer) on wound healing in a rodent model

Objective: To evaluate the effect of an artificial skin Hyphecan (1‐4,2‐acetamide‐deoxy‐B ‐D ‐glucan polymer) on wound healing in a rodent model. Materials and Method: The prospective study was conducted at a basic science laboratory at a tertiary teaching hospital. Two 4 cm × 4 cm full‐thickness wounds were created on the dorsal surface of 10 Spraque–Dawley rats and covered with Hyphecan and Kaltostat, respectively. Wounds were examined and measured on days 4, 10, 21 and 28, and would continue after day 28 until healed up completely. Punch biopsies (3 mm) were taken on days 4, 10 and 28 for histological examination of the response of healing and repair. Results: Despite the fact that the wound healing rate was similar for both groups on days 4, 10, 21 and 28, the average healing time for the Hyphecan group (29.1 ± 1.7 days) was significantly shorter statistically (P = 0.03) than the Kaltostat group (30.7 ± 2.8 days). Conversely, the marked healing response elicited by Hyphecan on day 4 persisted on days 10 and 28 in contrast to Kaltostat, which had only a mild degree of healing response on days 10 and 28. The study suggests that wounds treated by Hyphecan heal faster than Kaltostat. Conclusion: The findings provide basic scientific evidence supporting the clinical use of Hyphecan in different wounds and might also reduce the cost of wound management as Hyphecan is cheaper than Kaltostat and requires a shorter treatment time.      

Expression of human β‐defensin‐2 in the prostate

What’s known on the subject? and What does the study add? We found the expression of human β‐defensin‐2 (HBD‐2) in the prostate for the first time and LPS, a gram negative bacterial component, upregulated HBD‐2 in prostate epithelial cells. We are looking for other antimicrobial peptides expressed in the prostate besides human β‐defensin‐2. Also, we are studying the relationship between antimicrobial peptides and the development or progression of prostate diseases.

OBJECTIVE

To investigate the expression and regulation of human β‐defensin‐2 (HBD‐2) in the prostate.

PATIENTS AND METHODS

Normal human prostate epithelial cell line (RWPE‐1), human prostate cancer cell lines (DU‐145, PC‐3), and paraffin‐embedded prostate tissue from patients with benign prostatic hyperplasia (BPH) were analysed by RT‐PCR and immunohistochemical staining. HBD‐2 expression was also analysed by RT‐PCR and ELISA in RWPE‐1 cells treated with lipopolysaccharide (LPS). Nuclear factor‐κB (NF‐κB) activation was assessed by IκBα immunoblotting and electrophoretic mobility shift assay (EMSA).

RESULTS

BPH tissue and all of the tested prostate cell lines other than PC‐3 constitutively express HBD‐2 mRNA. HBD‐2 protein was strongly detected in prostate gland tissue surrounded by inflammatory cells including macrophages. Exposure to LPS induced HBD‐2 upregulation and NF‐κB activation, as assessed by IκBα phosphorylation and degradation in RWPE‐1 cells. Bay11‐7082, an NF‐κB inhibitor prevented LPS‐induced HBD‐2 production in RWPE‐1 cells.

CONCLUSIONS

Prostate epithelial cells may constitutively express HBD‐2, and its expression was upregulated by LPS. Our data indicate that HBD‐2 may be an important immunomodulatory factor in prostate function. Expression of HBD‐2 in normal prostates and the potential role of HBD‐2 in prostatitis and BPH should be addressed in the future.     

Hemorrhage‐Induced Interleukin‐1 Receptor Pathway in Lung Is Suppressed by 3,5‐Bis(2‐Fluorobenzylidene)‐4‐Piperidone in a Rat Model of Hypovolemic Shock

Severe blood loss in victims of trauma creates an exaggerated inflammatory background that contributes to the development of intravascular coagulopathy and multiple organ dysfunction syndrome. We hypothesized that treatment with diphenyldifluoroketone EF24, an inhibitor of nuclear factor kappa‐B, would have salutary effects in hemorrhagic shock. The objective of this study was to investigate the effect of EF24 on the expression of the interleukin‐1 receptor (IL‐1R) superfamily in a rat model of hypovolemic shock. Hypovolemia was induced by gradually withdrawing approximately 50% of circulating blood, and EF24 was administered intraperitoneally (0.2 mg/kg) in 50 μL of saline. After 6 h of shock, lung tissue was probed immunohistochemically and by immunoblotting to study the expression of Toll‐like receptor 4 (TLR4), IL‐1R, suppression of tumorigenicity 2 (ST2), and single immunoglobulin IL‐1R‐related (SIGIRR). The tissue‐associated pro‐inflammatory cytokines, tumor necrosis factor alpha (TNF‐α) and IL‐6, were measured by enzyme‐linked immunosorbent assay. We observed a reduction in immunoreactive TLR4 and IL‐1R1 in lung tissue of rats treated with EF24. Simultaneously, the pulmonary expression of ST2 and SIGIRR (the putative down‐regulators of the pro‐inflammatory IL‐1R pathway) was increased in EF24‐treated hemorrhaged rats. The concentration of hemorrhage‐induced TNF‐α and IL‐6 in lung tissue homogenates was also reduced by EF24 treatment. These results confirm our previous in vitro observations in lipopolysaccharide‐stimulated dendritic cells that EF24 beneficially modulates the IL‐1R pathway and suggest that it could be investigated as an adjunct therapeutic in managing inflammation associated with hemorrhagic shock.