Predictive value of Tc-99m galactosyl human serum albumin liver SPECT on the assessment of functional recovery after partial hepatectomy: a comparison with CT volumetry

Objective

Predicting liver functional reserve is important before partial hepatectomy. However, it is difficult to predict using morphologic imaging modalities, such as CT and MRI. In this study, we assess the usefulness of galactosyl human serum albumin (GSA) scintigraphy in predicting liver function recovery.

Methods

We performed ^99mTc-GSA scintigraphy before operation in 56 patients. Each patient was administered 185 MBq of ^99mTc-GSA by intravenous injection. Serial images were taken immediately after the administration for 40 min. SPECT images were obtained to make a functional map. We calculated the functioning parameter residual GSA-Rmax (GSA-RL) using analysis software developed by Dr. N. Shuke. In addition, we compared GSA-RL with the morphological parameter residual liver volume (RLV-CT) calculated by conventional CT and serum albumin (Alb) or cholinesterase (ChE). We analyzed the correlation between imaging parameters and the postoperative recovery periods of serum albumin (r-Alb) and cholinesterase (r-ChE) and the values at 1 and 3 months for serum albumin (1M-Alb, 3M-Alb) and cholinesterase (1M-ChE, 3M-ChE).

Results

We found significant correlations between GSA-RL and r-Alb, r-ChE, 1M-Alb, 3M-Alb, 1M-ChE and 3M-ChE, but not between RLV-CT and the same parameters.

Conclusion

The GSA-RL calculated by ^99mTc GSA-SPECT was a useful parameter for predicting postoperative liver function recovery that should be implemented before partial hepatectomy.     

Self-associating IgG rheumatoid factors in MRL/l autoimmune mice

Previous work has shown that the intermediate complexes isolated from the plasma of patients with rheumatoid arthritis are composed of self-associating IgG rheumatoid factors. Mice of the MRL/l strain develop spontaneous autoimmune disease with arthritis that is pathologically similar to human rheumatoid arthritis. Also, the sera of MRL/l mice contain autoantibodies to nuclear antigens as well as IgM and IgG rheumatoid factors. The present studies were done to determine if the IgG rheumatoid factors isolated from these mice undergo self-association. MRL/l mouse sera were categorized into groups A and B based on serum-serum precipitin interactions. Thirteen of 13 MRL/l mice sera examined contained intermediate complexes sedimenting between the 6.6S and 19S components of normal serum by sedimentation velocity ultracentrifugation. There were no differences in the level of intermediate complexes between groups A and B. IgG rheumatoid factors were isolated from the sera of 9 other mice. Upon sedimentation equilibrium ultracentrifugation, these rheumatoid factors underwent concentration-dependent self-association similar to that described for human self-associating IgG rheumatoid factors, although the precise stoichiometry of self-association could not be determined. The IgG rheumatoid factors from group B had higher energies of self-interaction than those from group A. These studies provide additional evidence that MRL/l mice may be the best available animal model for the study of human rheumatoid arthritis.     

Comparison of18F-fluoromethylcholine and 2-deoxy-D-glucose in the distribution of tumor and inflammation

PURPOSE: The distribution characteristics of 18F-fluoromethylcholine (18F-choline) in tumor and inflammatory tissue were compared with those of 14C or 3H-2-deoxyglucose (2DG) as a substitute for fluorodeoxyglucose (FDG). METHODS: A solid tumor model of AH 109A in the back of Donryu rats and an aseptic inflammation model of turpentine oil injection subcutaneously in rats were used for experiments. Tissue distribution was examined at 5, 30 and 60 min after injection of a mixture of 18F-choline and 3H-2DG. Double-tracer high-resolution autoradiographs (ARGs) of tumor and inflammation were obtained using 18F-choline and 14C-2DG. Whole body (WB) ARG was performed with 18F-choline. RESULTS: Tumor uptake of 18F-choline reached a peak at 30 min, when the tumor to blood ratio was 5.1. Both tumor and inflammation uptake of 2DG were higher than those of 18F-choline. 18F-choline uptake by inflammation was lower than that by tumor. The tumor to brain uptake ratio was 5.7 with 18F-choline and 1.2 with 2DG. In the ARG of inflammation, linear or ring-like structures of 2DG uptake were observed in the wall of the abscess, but were not identified with 18F-choline. Photomicrography showed that the uptake was limited to granulocytes, macrophages and fibroblasts, consistent with sub-acute or chronic inflammation. CONCLUSION: 18F-choline uptake by inflammation was lower than that of 2DG in the tissue distribution study, and 18F-choline uptake by abscess wall was significantly lower than that of 2DG in the autoradiography study. Our results may suggest the feasibility of 18F-choline-PET imaging for the differential diagnosis of cancer and chronic inflammation in lung and brain.     

Interventional radiologic treatment for idiopathic portal hypertension

Purpose: To evaluate the usefulness of interventional radiological treatment for idiopathic portal hypertension. Methods: Between 1995 and 1998, we performed an interventional radiological treatment in five patients with idiopathic portal hypertension, four of whom had refused surgery and one of whom had undergone surgery. Three patients with gastroesophageal varices (GEV) were treated by partial splenic embolization (PSE), one patient with esophageal varices (EV) and massive ascites by transjugular intrahepatic portosytemic shunt (TIPS) and PSE, and one patient with GEV by percutaneous transhepatic obliteration (PTO). Midterm results were analyzed in terms of the effect on esophageal and/or gastric varices. Results: In one woman with severe GEV who underwent three sessions of PSE, there was endoscopic confirmation that the GEV had disappeared. In one man his EV shrunk markedly after two sessions of PSE. In two patients slight reduction of the EV was obtained with one application of PSE combined with endoscopic variceal ligation therapy. PTO for GV in one patient resulted in good control of the varices. All patients have survived for 16–42 months since the first interventional treatment, and varices are well controlled. Conclusion: Interventional radiological treatment is effective for patients with idiopathic portal hypertension, whether or not they have undergone surgery.     

Studies of human visual pathophysiology with visual evoked potentials.

Visual evoked potentials (VEPs) offer reproducible and quantitative data on the function of the visual pathways and the visual cortex. Pattern reversal VEPs to full-field stimulation are best suited to evaluate anterior visual pathways while hemi-field stimulation is most effective in the assessment of post-chiasmal function. However, visual information is processed simultaneously via multiple parallel channels and each channel constitutes a set of sequential processes. We outline the major parallel pathways of the visual system from the retina to the primary visual cortex and higher visual areas via lateral geniculate nucleus that receive visual input. There is no best method of stimulus selection, rather visual stimuli and VEPs' recording should be tailored to answer specific clinical and/or research questions. Newly developed techniques that can assess the functions of extrastriate as well as striate cortices are discussed. Finally, an algorithm of sequential steps to evaluate the various levels of visual processing is proposed and its clinical use revisited.     

Factor VIII contributes to platelet-fibrin thrombus formation via thrombin generation under low shear conditions

Introduction

Thrombus growth under low blood flow velocity plays an important role in the development of deep venous thrombosis (DVT). Increased plasma levels and activities of coagulation factor VIII (FVIII) comprise risk factors for DVT and pulmonary thromboembolism.

Objective

To localize FVIII in human venous thrombi of DVT and to determine whether FVIII contributes to thrombus formation under low shear conditions.

Methods

The localization of FVIII in venous thrombi obtained from patients with DVT was examined by immunohistochemistry. The role of FVIII in thrombus formation was investigated using a flow chamber system. Venous blood from healthy volunteers were incubated with an anti-FVIII monoclonal antibody (VIII-3776) or non-immunized mouse IgG₁. Blood samples were perfused on immobilized type III collagen at wall shear rates of 70/s and 400/s and then the surface area covered by platelets and fibrin was morphometrically evaluated. Prothrombin fragment 1+2 (PF1+2) generation was measured before and after perfusion.

Results

Venous thrombi of DVT comprised a mixture of platelets, fibrin and erythrocytes. Factor VIII appeared to be colocalized with glycoprotein IIb/IIIa, fibrin and von Willebrand factor in the thrombi. VIII-3776 specifically recognized the light chain of FVIII and prolonged the activated partial thromboplastin time (aPTT), but not prothrombin time (PT). The antibody significantly reduced platelets and fibrin covering, as well as PF1+2 generation at wall shear rates of 70/s and 400/s.

Conclusions

These results suggest that FVIII contributes to platelet aggregation and fibrin formation via thrombin generation under low shear conditions.     

A Novel Modification of Traditional 2-Port Laparoscopic Surgery Using a 5-mm Flexible Scope

In embryonic natural orifice transumbilical endoscopic surgery, more than 1 port is inserted through the umbilicus. In the present study, embryonic natural orifice transumbilical endoscopic surgery combined with a flexible scope was used to further improve gynecologic surgery. A surgical incision was made in the umbilical region to enter the abdominal cavity using the closed approach. A 12-mm port was placed at the umbilical incision, and the 5-mm flexible scope was inserted through the port. Another surgical port was then made in the left inguinal region for insertion of a 5-mm port while monitoring it with the flexible scope. The flexible scope was then inserted through the 5-mm inguinal port, and another 5-mm port was inserted caudal to the 12-mm port while monitoring the umbilical region with the flexible scope. The 12- and 5-mm ports were inserted through the same umbilical incision so that they were positioned vertically. The surgeon stood on the left side of the patient to manipulate the 12-mm umbilical port with the right hand and the 5-mm inguinal port with the left hand. An assistant surgeon inserted the flexible scope through the 5-mm umbilical port and manipulated it with the left hand to secure the view during surgery by appropriately adjusting the angle of the flexible scope. With the present technique, the flexible scope did not interfere with the forceps inside or outside of the body cavity because its angle could be freely set. Since March 2, 2009, we have performed 8 procedures using this surgical technique including 1 salpingectomy, 3 ovarian cystectomies, 2 total laparoscopic hysterectomies, 1 linear salpingostomy, and 1 total laparoscopic myomectomy. Intracorporeal suturing was performed in all cases but one because a suture needle could be easily inserted through the 12-mm port. Furthermore, total laparoscopic myomectomy could be completed using a 12-mm power mocellator inserted through the 12-mm port. The flexible scope and forceps did not hinder each other either inside or outside of the body cavity. Use of the flexible scope enables the conventional rigid straight forceps to be used in almost the same manner as with the conventional laparoscopic technique.     

Associations between components of the metabolic syndrome versus bone mineral density and vertebral fractures in patients with type 2 diabetes

The association of bone with the metabolic syndrome and its features, visceral fat accumulation or insulin resistance, remains unclear. We determined visceral and subcutaneous fat areas (V and S) by computed tomography on 187 men (28–83 years) and 125 postmenopausal women (46–82 years) with type 2 diabetes. Men whose V was 100 cm² or more had significantly lower urinary N-terminal cross-linked telopeptide of type-I collagen (p = 0.005), higher femoral neck bone mineral density (FN-BMD) (p = 0.004), and lower prevalence of vertebral fractures (VFs) (p = 0.04) than controls. Fat mass, V, S, and lean body mass positively correlated with FN-BMD in men and with lumbar (L) and FN-BMD in women. When adjusted for weight, these correlations became negative. Urinary C-peptide positively correlated with FN-BMD in both genders. Multivariate logistic regression analysis adjusted for age, height, weight, L-BMD, duration of diabetes, and diabetes therapies identified V in men and urinary C-peptide in women as factors inversely associated with the presence of VFs [odds ratio (OR) = 0.61 per SD increase, p = 0.04, and OR = 0.32, p = 0.01, respectively]. These findings suggest that, of the components of the metabolic syndrome, body fat in gravity and hyperinsulinemia could increase FN-BMD in diabetic subjects. Visceral fat in men and hyperinsulinemia in women may protect against VFs independent of weight, L-BMD, diabetes duration, or therapies.     

Alterations in expression of Cat‐315 epitope of perineuronal nets during normal ageing,and its modulation by an open‐channel NMDA receptor blocker,memantine

The perineuronal net (PNN), a specialized aggregate of the extracellular matrix, is involved in neuroprotection against oxidative stress, which is now recognized as a major contributor to age‐related decline in brain functions. In this study, we investigated the age‐related molecular changes of PNNs using monoclonal antibody Cat‐315, which recognizes human natural killer‐1 (HNK‐1) glycan on aggrecan‐based PNNs. Western blot analysis showed that the expression levels of Cat‐315 epitope in the hippocampus were higher in middle‐aged (MA, 12‐month‐old) mice than in young adult (YA, 2‐month‐old) mice. Although there were no differences in the expression levels of Cat‐315 epitope between old age (OA, 20‐month‐old) and MA mice, Cat‐315 immunoreactivity was also detected in astrocytes of OA mice. To focus on Cat‐315 epitope in PNNs, we used YA and MA mice in the following experiments. Optical disector analysis showed that there were no differences in the numbers of Cat‐315‐positive (Cat‐315⁺) PNNs between YA and MA mice. Fluorescence intensity analysis indicated that Cat‐315 immunoreactivity in PNNs increased with age in the dorsal hippocampus, which is mainly involved in cognitive functions. Administration of an open‐channel blocker of NMDA receptor, memantine, reduced the expression levels of Cat‐315 epitope in the hippocampus. Furthermore, the numbers of glutamatergic and GABAergic terminals colocalized with Cat‐315 epitope around parvalbumin‐positive neurons were decreased by memantine. These findings provide novel insight into the involvement of PNNs in normal brain ageing, and suggest that memantine may counteract the age‐related alterations in expression levels of Cat‐315 epitope via regulation of its subcellular localization.     

Stereological estimation of numerical densities of glutamatergic principal neurons in the mouse hippocampus

Recent studies have emphasized functional dissociations between dorsal and ventral hippocampus in learning, emotion, and affect. A rigorous quantitative analysis concerning lamellar cytoarchitecture would be important for promoting further research on the regional differentiation of the hippocampus. Here, we stereologically estimated the numerical densities (NDs) of glutamatergic principal neurons in the mouse hippocampus and encountered the significant differences along the dorsoventral axis. In the CA1 region, the NDs of CA1 pyramidal neurons were almost three times higher at the dorsal level (447.5 × 10³/mm³) than at the ventral level (180.5 × 10³/mm³); meanwhile, along the transverse axis, the NDs were significantly higher in the proximal portion than in the distal portion both at the dorsal and ventral levels. An EF‐hand calcium‐binding protein, calbindin D28K, was expressed in ∼45% of CA1 pyramidal neurons both at the dorsal and ventral level. In the CA3 region, there were no significant differences in the NDs along the dorsoventral and transverse axes (dorsal, 165.2 × 10³/mm³; ventral, 172.4 × 10³/mm³). In the dentate gyrus (DG), the NDs of granule cells were significantly higher at the dorsal level (916.7 × 10³/mm³) than at the ventral level (788.9 × 10³/mm³). The significant differences were observed only in the suprapyramidal blade, but not in the infrapyramidal blade. Then, we calculated the total neuron numbers contained in a 300‐μm‐thick hypothetical transverse slice of the hippocampus and found that the ratios of GABAergic to glutamatergic neuron numbers were two to three times higher in the ventral slice than in the dorsal slice. The ratios of numbers of eight GABAergic neuron subtypes to principal cells indicate structural dissociations in the neural network between dorsal and ventral slices. These findings provide an essential quantitative basis for elucidating mechanisms of distinct neural circuits underlying various hippocampal functions. © 2009 Wiley‐Liss, Inc.