Biomedical subjects

Ryuichi Nishii

Publications and source records attributed to Ryuichi Nishii.

14 recordsLinked to original sources

PubMed2006

Radioiodinated VEGF to image tumor angiogenesis in a LS180 tumor xenograft model.

INTRODUCTION: Angiogenesis is essential for tumor growth or metastasis. A method involving noninvasive detection of angiogenic activity in vivo would provide diagnostic information regarding antiangiogenic therapy targeting vascular endothelial cells as well as important insight into the role of vascular endothelial growth factor (VEGF) and its receptor (flt-1 and KDR) system in tumor biology. We evaluated radioiodinated VEGF(121), which displays high binding affinity for KDR, and VEGF(165), which possesses high binding affinity for flt-1 and low affinity for KDR, as angiogenesis imaging agents using the LS180 tumor xenograft model. METHODS: VEGF(121) and VEGF(165) were labeled with (125)I by the chloramine-T method. Biodistribution was observed in an LS180 human colon cancer xenograft model. Additionally, autoradiographic imaging and immunohistochemical staining of tumors were performed with (125)I-VEGF(121). RESULTS: (125)I-VEGF(121) and (125)I-VEGF(165) exhibited strong, continuous uptake by tumors and the uterus, an organ characterized by angiogenesis. (125)I-VEGF(121) uptake in tumors was twofold higher than that of (125)I-VEGF(165) (9.12+/-98 and 4.79+/-1.08 %ID/g at 2 h, respectively). (125)I-VEGF(121) displayed higher tumor to nontumor (T/N) ratios in most normal organs in comparison with (125)I-VEGF(165). (125)I-VEGF(121) accumulation in tumors decreased with increasing tumor volume. Autoradiographic and immunohistochemical analyses confirmed that the difference in (125)I-VEGF(121) tumor accumulation correlated with degree of tumor vascularity. CONCLUSION: Radioiodinated VEGF(121) is a promising tracer for noninvasive delineation of angiogenesis in vivo.

Angiostatins↗

PubMed2006

Alteration of regional cerebral blood flow in patients with chronic pain--evaluation before and after epidural spinal cord stimulation.

BACKGROUND: Chronic pain is defined as intractable pain caused by abnormal pain transmission or impairment of the pain control system per se. Alteration of regional cerebral blood flow (rCBF) is known to occur under the presence of pain stimulation. Epidural spinal cord stimulation (SCS) is occasionally effective in relieving the symptom. OBJECTIVE: The aim of the current study is to investigate the alteration of rCBF in baseline condition and to find the association between the rCBF change and the efficacy of SCS in chronic pain. METHODS: A total of 18 patients underwent Tc-99m-HMPAO SPECT before and after SCS. Analysis with three-dimensional stereo-tactic surface projections (3D-SSP) with stereo-tactic extraction estimation (SEE) software was adopted to evaluate the rCBF. We assessed the extent score of the abnormal region in each segment (rate of the coordinates with a Z-value that exceeds three kinds of threshold value 2.0, 2.5 and 3.0 in all coordinates within a segment). According to the therapeutic response defined by visual analogue scale, we categorized patients into two groups, the good responder (GR) group (n=12) and poor responder (PR) group (n=6). In the analysis, we compared the extent score in the following two conditions. (1) Comparison between the PR group and normal control group under both baseline condition and after SCS. (2) Comparison between the GR group and normal control group under both baseline condition and after SCS. RESULTS: (1) In the PR group, increased rCBF was observed in left thalamus, bilateral precuneus and bilateral cerebellum under the baseline condition. After SCS, the range of these increased rCBF areas localized but remained. Decrease of rCBF was noted in bilateral subcallosal gyrus, superior temporal gyrus (STG) and bilateral anterior cingulate gyrus (ACG). They localized after SCS, but remained. (2) In the GR group, increased rCBF areas were noted in bilateral precuneus and bilateral cerebellum under the baseline condition. After SCS, they localized in bilateral precuneus but those of bilateral cerebellum remained. Decreased rCBF area was noted in bilateral subcallosal gyrus, STG and bilateral ACG under the baseline. After SCS, they localized in bilateral subcallosal gyrus and bilateral STG. In contrast, they enlarged in bilateral ACG. CONCLUSION: Chronic pain patients demonstrated abnormal rCBF distribution on both baseline and post SCS conditions. Increased rCBF of thalamus and precuneus under both conditions in the PR group and decreased rCBF of ACG under post SCS conditions in the GR group were characteristic patterns. Tc-99m-HMPAO SPECT with 3D-SSP and SEE analysis is likely objective and effective in monitoring and evaluating therapeutic outcome by SCS in chronic pain. In addition, it provides information that is useful in the selection of SCS candidates.

Brain↗

PubMed2006

Detection of maleate-induced Fanconi syndrome by decreasing accumulation of 125I-3-iodo-alpha-methyl-L-tyrosine in the proximal tubule segment-1 region of renal cortex in mice: a trial of separate evaluation of reabsorption.

OBJECTIVE: Fanconi syndrome is a renal dysfunction characterized by various combinations of renal tubular transport dysfunction involving amino acids, glucose, protein and other substances. Most reabsorption of amino acids occurs in proximal renal tubule segment 1 (S1). The present study evaluated the possibility of early detection of drug-induced Fanconi syndrome, based on decreased renal accumulation of 125I-3-iodo-alpha-methyl-L-tyrosine (125I-IMT), an amino acid transport marker, in the S1 region of renal cortex. The present experimental model used maleate (MAL)-induced Fanconi syndrome in mice. Results were compared between 125I-IMT and 3 other clinical renal radiopharmaceuticals: 99mTc-2,3-dimercaptosuccinic acid (99mTc-DMSA); 99mTc-mercaptoacetylglycylglycylglycine (99mTc-MAG3); and 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA). METHODS: Male ddY mice (age, 6 weeks; body weight, 25 g) were used to create a Fanconi model of renal dysfunction. A single dose of maleate disodium salt was administered by intraperitoneal injection (6 mmol/kg). Hematoxylin and eosin (HE) staining of the renal cortex, renal autoradiography and measurement of renal radioactivity of labeled compounds were performed at 30, 60, 90 and 120 min after MAL injection. At 5 min after injection of labeled compounds (18.5 kBq for accumulation experiment, 670 kBq for autoradiography), animals were sacrificed by ether overdose and kidneys were removed. For the accumulation experiment, radioactivity was measured using a well-type scintillation counter. For autoradiography, 20-microm sections of frozen kidney were used with Bio-Imaging Analyzer. RESULTS: At 30 min after MAL injection, HE staining showed pyknosis in some proximal tubule cells. At that time, accumulations of 125I-IMT and 99mTc-DMSA in the S1 region were approximately 67% and 55% of control levels (p < 0.005). MAL increased accumulation of 99mTc-DTPA in the S1 region, but had no effect on accumulation of 99mTc-MAG3 in the S 1 region. CONCLUSIONS: Decreased accumulation of 123I-IMT in the S1 region appears to represent a useful marker for detection of MAL-induced Fanconi syndrome. In future, we plan to assess the efficacy of using 125I-IMT to monitor renal dysfunction induced by nephrotoxic clinical drugs.

Absorption↗

PubMed2006

Relationship between cancer cell proliferation, tumour angiogenesis and 201Tl uptake in non-small cell lung cancer.

PURPOSE: To investigate whether 201Tl uptake is associated with cell proliferation and angiogenesis in non-small-cell lung carcinoma (NSCLC). METHODS: Eighty-four patients with scheduled NSCLC underwent 201Tl single photon emission computed tomography (SPECT) imaging: 15 min (early scan) and 240 min (delayed scan) after intravenous injection of 111 MBq of 201Tl chloride. 201Tl indices were calculated on early images (early ratio: ER) and delayed images (delayed ratio: DR). The retention index (RI) was also calculated from these two parameters. Using surgically resected cancer specimens (54 adenocarcinoma, 24 squamous cell carcinoma (SCC), six large-cell carcinoma), immunohistochemical stains for both Ki-67 (MIB-1 index) and CD34 were performed to examine the proliferative activity and the micro-vessel density (MVD), respectively. RESULTS: The mean value of 201Tl index was 1.69+/-0.77 (ER) and 2.31+/-1.08 (DR). The average RI was 42.6+/-42.9%, respectively. Both DR and RI positively correlated with MIB-1 index (r = 0.68, P < 0.05 and r = 0.52, P < 0.05). When we analyse adenocarcinoma and SCC separately, there was a significant positive correlation (r = 0.62, P < 0.05) between RI and MIB-1 index in adenocarcinoma but not in SCC (r = 0.20, P = NS). The value of ER positively correlated with MVD (r = 0.75, P < 0.05). It demonstrated strong positive correlation with both histological types (adenocarcinoma: r = 0.80, P < 0.05, SCC: r = 0.66, P < 0.05). CONCLUSION: 201Tl SPECT imaging is effective non-invasive method for assessing both the proliferation and the angiogenesis in NSCLC. Both DR and RI are useful indicators for assessing cancer cell proliferation in lung adenocarcinoma. ER is a useful marker for assessing the tumour angiogenesis in NSCLC.

Adult↗

PubMed2005

Significant clinical differences in primary hyperparathyroidism between patients with and those without concomitant thyroid disease.

PURPOSE: We evaluated the differences in diagnosis and treatment for primary hyperparathyroidism (pHPT) in patients with and those without concomitant thyroid disease. METHODS: One hundred and ten patients with pHPT underwent parathyroid localization and thyroid examination by ultrasonography (US) and sestamibi scintigraphy (MIBI). The clinical and biochemical findings, parathyroid localization, and operations performed were compared in 49 patients without thyroid disease and 61 patients with thyroid disease. RESULTS: Asymptomatic hypercalcemia was significantly more prevalent in patients with concomitant thyroid disease (88.5%) than in those without thyroid disease (49.0%) (P < 0.01). The mean serum calcium was significantly higher and the inorganic phosphate level was significantly lower in patients without concomitant thyroid disease than in those with concomitant thyroid disease (P < 0.05, P < 0.01, respectively). The pathologic parathyroid gland was identified significantly more often in patients without concomitant thyroid disease than in those with concomitant thyroid disease both by US and MIBI (P < 0.05). Unilateral exploration was performed more often in patients without thyroid disease than in those with thyroid disease (P < 0.01). CONCLUSION: Primary hyperparathyroidism was diagnosed at an earlier stage in patients with concomitant thyroid disease. Thyroid disease concomitant with pHPT influenced parathyroid localization as well as the indication for minimally invasive parathyroidectomy.

Adult↗

PubMed2005

Thyroid evaluation in patients with primary hyperparathyroidism.

We evaluated the efficacy of preoperative high-resolution ultrasonography (US) for diagnosing possible concomitant thyroid disease which affects the surgical management in patients with primary hyperparathyroidism (pHPT). One hundred and nine patients with sporadic pHPT underwent US with or without ultrasound-guided fine-needle aspiration biopsy (US-FNAB). Diagnosis of concomitant thyroid nodules by US and US-FNAB were compared with the histopathological findings. Of the 109 patients, 19 (17.4%) had malignant thyroid nodules, 26 (23.9%) had benign thyroid nodules alone, and 12 (11.0%) had diffuse goiter. The sensitivity, specificity, and accuracy of diagnosing 72 thyroid nodules were 91.3%, 91.8%, and 91.7% for US, 57.9%, 94.3%, and 81.5% for US-FNAB, and 95.7%, 91.8%, and 93.1% for combined US and US-FNAB, respectively. True positive/false negative ratio of US-FNAB diagnosis was significantly lower in nodules of 5-9 mm than nodules of 10 mm or more. Four unexpected thyroid cancers existed at a different site in 3 of the 39 patients with palpable thyroid disease. Five thyroid cancers were histopathologically confirmed in 5 (7.1%) of 70 patients without palpable thyroid disease. Eight (88.9%) of the 9 non-palpable thyroid cancers were accurately diagnosed by combined US and US-FNAB. Preoperative US is useful for evaluation of possible concomitant thyroid disease, especially for prediction of malignancy.

Adenoma↗

PubMed2004

Cerebral blood flow abnormalities induced by transient hypothyroidism after thyroidectomy--analysis by tc-99m-HMPAO and SPM96.

UNLABELLED: The current study is an investigation of alterations in regional cerebral blood flow (rCBF) distribution in patients with transient hypothyroidism after thyroidectomy. In addition, the effects of thyroxine treatment on rCBF changes were studied. METHODS: Noninvasive rCBF measurements using 99mTc-HMPAO SPECT were performed on 24 post-thyroidectomy patients who were in a hypothyroidic state. The measurements were conducted before 131I therapy and after thyroid hormone (thyroxine) replacement. We used adjusted rCBF images (normalization of global CBF for each subject to 50 ml/100 g/min with proportional scaling) to compare these data with age-matched normal control groups (n =15) using SPM96. We also compared the absolute rCBF value of hypothyroidic patients with those of normal control groups. In addition, the association between rCBF alteration and the severity of depression was also analyzed. Finally, the effect of thyroid hormone replacement on rCBF was investigated individually using the Jack-knife test, in which patient data were compared with those from healthy volunteers. According to the result of this test, all cases were categorized into three subgroups, namely, improved, unchanged group and normal. To prove the reversibility of rCBF alteration after thyroid hormone replacement, a group comparison test between the normal controls and the improved group was done before and after thyroid hormone replacement. Similarly a group comparison test between the unchanged group and normal controls was also performed. RESULTS: In the hypothyroidic condition, there was a significant decrease in the posterior part of the bilateral parietal lobes and in part of the bilateral occipital lobes, including the cuneus. These decreased rCBF areas extended to the bilateral prefrontal cortices as deterioration became more profound. On individual analysis, 16 of 24 patients (66.7%) demonstrated rCBF reduction, while 8 patient did not show significant rCBF change (33.3%, the normal group). After thyroxine replacement, improvement of rCBF was noted in nine of 16 patients (56.3%, the improved group). In seven of 16 patients (43.7% the unchanged group), the significant low rCBF area remained unchanged. Compared with the normal controls, the improved group showed significantly decreased rCBF of the bilateral parietal lobe and the occipital lobe in the hypothyroic condition. After thyroid hormone replacement, these abnormal rCBF areas disappeared. In contrast, in the unchanged group, the significant hypoperfusion area became localized but remained. CONCLUSION: 99mTc-HMPAO SPECT and SPM96 analysis demonstrated a significant rCBF decrease in the parietal lobe and part of the occipital lobe in patients with induced transient hypothyroidism after thyroidectomy. This phenomenon might contribute to understanding of the depressive state. Recovery of rCBF after thyroid hormone replacement was confirmed in some patients. However, rCBF improvement did not always occur in every patient during the follow up period. The reversibility of rCBF in transient hypothyroidism may be dependent on individual characteristics during a short-term period.

Adult↗

PubMed2004

Renal accumulation and excretion of radioiodinated 3-iodo-alpha-methyl-L-tyrosine.

OBJECTIVE: We investigated mechanisms of renal accumulation of radioiodinated 3-iodo-alpha-methyl-L-tyrosine (IMT), which has been used clinically for tumor imaging and as an amino acid transport marker in studies of brain and pancreas function. METHODS: In this study, we used 125I- or 123I-labeled IMT ([125I]IMT or [123I]IMT) as the transport marker. Partition coefficients of [125I]IMT were determined for hypothetic urine at pH ranging from 5 to 8. The examination of uptake and inhibition of [125I]IMT was performed using normal human renal proximal tubule epithelial cells (RPTEC), which are characteristic of the proximal convoluted tubule. The plasma protein binding ratio of [125I]IMT was determined using rats. In the in vivo experiments using mice, we examined biodistribution and excretion inhibition, and performed whole body autoradiography. Also, renal SPECT using [123I]IMT was performed using a normal canine. RESULTS: Very low lipophilicity of [125I]IMT in hypothetic urine suggests that a carrier-mediated pathway contributes to its marked kidney accumulation. [125I]IMT uptake into RPTEC was significantly inhibited by 2-aminobicyclo[2,2,1]heptane-2-carboxylic acid (BCH) in a sodium-dependent manner, suggesting reabsorption mainly via system B0 in apical membrane of proximal tubule. Plasma protein binding ratio of IMT was 45.4 +/- 5.6%. At 6 hr after administration of IMT to mice, excretion via urinary tract was 77.51% of injected dose, and excretion into feces was 0.25%. Furosemide, ethacrynic acid and probenecid inhibited tubular secretion of [125I]IMT in mice. We obtained very clear autoradiographs of mouse renal cortex and a canine renal SPECT image (S2-like region). CONCLUSIONS: We believe that [123I]IM-T is useful for kidney imaging. In future studies, we plan to examine the use of [123I]IMT in diagnosis of disease.

Animals↗

PubMed2004

[Usefulness of 201Tl SPECT in the predication of mediastinal lymph nodes metastasis in patients with non small cell lung carcinoma (NSCLC)].

Predictivity of mediastinal lymph nodes metastasis of 201Tl SPECT were examined before operation in 113 patients with non-small cell lung cancer (69 adenocarcinoma, 31 squamous cell carcinoma, 10 large cell carcinoma, 2 bronchiolo-alveolar carcinoma, 1 neuroendocrine cell carcinoma). Patients were classified into two groups, with or without lymph nodes metastasis according to the pathological diagnosis. We calculated parameters of 201Tl SPECT early ratio, delayed ratio, retention index (RI) and maximal diameters. In addition, we calculated optimal cut-off value of RI to estimate the mediastinal lymph nodes metastasis. Mediastinal lymph nodes metastasis was confirmed pathologically in 62 patients. ER and DR did not show any statistical significance between two groups. Maximal diameters of primary tumor were also comparable between two groups. RI was significantly higher in mediastinal lymph node metastasis positive group compared to that in mediastinal lymph node metastasis negative group. The sensitivity (Sen), specificity (Spe), positive predictive value (PPV), negative predictive value (NPV) and accuracy (Acc) of 201Tl SPECT were 82.2%, 82.3%, 85.0%, 79.2% and 82.3%. These parameters were similar of higher than 72.6%, 82.4%, 83.3%, 71.2% and 77.0% of chest CT. The RI of 201Tl SPECT was useful tool for predicting lymph nodes metastasis in non-small cell lung cancer. The optimum cut-off value of RI in the prediction of mediastinal lymph nodes metastasis was 35%. We should take into account of upstaging in cases with higher RI (>35%).

Adult↗

PubMed2003

An artificial amino acid, 4-iodo-L-meta-tyrosine: biodistribution and excretion via kidney.

UNLABELLED: We evaluated the use of radiolabeled 4-iodo-L-meta-tyrosine as an amino acid transport marker. The pharmacologic features of this compound, particularly the biodistribution and excretion, were examined by conducting in vivo and in vitro studies using 4-(125)I-iodo-L-meta-tyrosine (4-(125)I-mTyr). Results obtained for L-(14)C-Tyr and 3-(125)I-iodo-alpha-methyl-L-tyrosine ((125)I-IMT) were used for comparison. METHODS: In vivo biodistribution studies of 4-(125)I-mTyr were performed in male ddY mice. Urinary excretion of 4-(125)I-mTyr and (125)I-IMT with administration of probenecid was studied. Local distribution of 4-(125)I-mTyr and (125)I-IMT in kidney was visualized by autoradiography. We performed metabolite analysis of 4-(125)I-mTyr in mice. For in vitro studies, reabsorption mechanisms of 4-(125)I-mTyr were compared with those of (125)I-IMT and the parent L-(14)C-Tyr using superconfluent monolayers of the porcine kidney epithelial cell line LLC-PK(1) in medium containing inhibitor (L-Tyr, D-Tyr, and 2,4-dinitrophenol), in Na(+)-free medium, and at 4 degrees C. RESULTS: 4-(125)I-mTyr demonstrated high accumulation in the pancreas and kidney and comparable brain uptake to that of (125)I-IMT. Blood clearance of 4-(125)I-mTyr was faster than that of (125)I-IMT. Three hours after administration, >70% of 4-(125)I-mTyr was excreted via the urine, whereas <5% was found in the feces. Renal autoradiography revealed moderate accumulation of 4-(125)I-mTyr and high accumulation of (125)I-IMT in the renal cortex. Probenecid further reduced accumulation of 4-(125)I-mTyr and (125)I-IMT in the kidney as well as urinary excretion. At 30 min after tracer injection, intact free 4-(125)I-mTyr accounted for >98.1% of the total present in kidney and >96.3% in urine. Protein incorporation was not observed. Uptake of 4-(125)I-mTyr into LLC-PK(1) cell monolayers was remarkably reduced by 5 mmol/L L-Tyr (4.6%) and incubation at 4 degrees C (15.6%) but was reduced by 5 mmol/L D-Tyr (50.0%). L-(14)C-Tyr and (125)I-IMT showed similar results; however, uptake of (125)I-IMT was enhanced by 0.1 mmol/L 2,4-dinitrophenol (165.1%), an inhibitor of generation of energy-rich phosphates. CONCLUSION: The artificial amino acid 4-(125)I-mTyr demonstrated high metabolic stability, rapid blood clearance, rapid urinary excretion, and similar biodistribution to other radiolabeled L-Tyr analogs. 4-(125)I-mTyr can be a competitive substrate of L-Tyr reabsorption. However, 4-(125)I-mTyr demonstrates different pharmacologic features than those of (125)I-IMT, particularly in renal handling. 4-(125)I-mTyr may potentially be applied as a new amino acid transport marker.

Amino Acids↗

PubMed2003

[The development of new method for the assessment of perfusion reserve using split dose iodine-123-IMP SPECT: one-day protocol by modified ARG method].

Evaluation of the regional cerebrovascular reactivity (rCVR) to a cerebral vasodilatory stimulus is important in the investigation of patients with ischemic cerebrovascular disease. We devised a simplified one-day protocol technique using [123I]N-isopropyl-p-iodoamphetamine (IMP) autoradiography (ARG) with SPECT. To validate the accuracy of IMP-ARG for quantifying rCVR to acetazolamide, we compared rCVR measured using IMP-ARG with rCVR calculated using IMP split dose method of microsphere model. Twenty patients with chronic steno-occlusive disease in a unilateral major cerebral artery underwent 123I-SPECT. On rCBF SPECT image above 3.5 cm from OM line, large cortical regions of interest (ROI) was bilaterally determined for bilateral middle cerebral artery and anterior cerebral artery. Based on rCBF values in each ROI, rCVR to acetazolamide was calculated. Significant correlation was observed between rCVR values obtained using IMP-ARG and microsphere model IMP methods in the 80 ROIs examined in the 20 patients (r = 0.72; p < 0.001). The result demonstrated that [123I]IMP-ARG split dose method can quantify rCVR non-invasively in a short time.

Aged↗

PubMed2002

Prediction of plasma concentration-time curve of orally administered theophylline based on a scintigraphic monitoring of gastrointestinal transit in human volunteers.

The plasma concentration-time profile of theophylline after oral administration in human volunteers was predicted using the individual gastrointestinal (GI) transit data monitored by a gamma scintigraphic technique. Theophylline was administered as aminophylline under fasted and fed condition, along with 99mTc-labeled diethylenetriamine-pentaacetic acid (DTPA), an unabsorbable marker to evaluate the GI transit by a gamma scintigraphic technique. Two healthy male volunteers participated under fasted and fed conditions in a crossover study. The GI transit was evaluated by dividing the GI tract to four segments, stomach, jejunum, ileum and cecum/colon. Under the fed condition, the GI transit pattern for each segment was confirmed to alter considerably, causing a delay in the gastric emptying mainly. Further, the plasma concentration curves of theophylline after oral administration were predicted using the GI-Transit-Absorption Model on the basis of individual GI transit parameters calculated by the fitting of the observed data to the GI-Transit Kinetic Model. The absorption rate constant in each segment and the pharmacokinetic parameters after intravenous administration used for the prediction were the values extrapolated from the data in rats and the ones normalized from the values in literatures, respectively. The plasma concentration-time curves for theophylline were well predicted using obtained individual GI transit parameters. The analysis using this method could estimate the variable absorption behavior governed by the GI transit in detail.

Administration, Oral↗

PubMed2002

Serial change in 123I-MIBG myocardial scintigraphy in non-insulin-dependent diabetes mellitus.

PURPOSE: We performed 123I-MIBG (MIBG) myocardial scintigraphy twice in patients with non-insulin-dependent diabetes mellitus (NIDDM) to investigate whether MIBG distribution was improved by pertinent clinical control. To determine the influential factors for MIBG distribution, we investigated the association between various clinical parameters and the serial change in MIBG uptake parameters. PATIENTS AND METHODS: Twenty NIDDM patients with no cardiac disorders were evaluated. Planar images were taken at 30 minutes (early) and 3 hours (delayed) after MIBG injection. The heart-to-upper-mediastinum uptake ratio (H/M) and washout ratio (WR) were calculated as parameters for estimating cardiac sympathetic function. Patients were divided into two groups, eight in the improved group and twelve in the unimproved group, according to the serial change in H/M. The mean interval between the baseline and the follow up study was 2.1 +/- 0.6 year. Differences between the means of the laboratory data in patients in both groups were compared for the baseline and the follow up study by using the paired t-test. As a means of determining the influential factors for a serial change of MIBG uptake, Fisher's exact test was performed to evaluate the association between the serial change in cardiac MIBG parameters and changes in other clinical parameters, such as blood sugar (BS) control, BS control method (insulin therapy), serum cholesterol control, and severity of diabetic complications. We also analyzed the association between the changes in CV(R-R) (coefficient variance of R-R intervals at rest ECG) or NCV (velocity of posterior tibial nerve) and those of other clinical parameters. Associations among these neurological parameters (MIBG parameters, CV(R-R) and NCV) were also analyzed. RESULTS: Paired t-tests showed a significant decrease in fasting blood sugar and fructosamine in the improved group in the follow up study compared to those in the baseline study. Nevertheless, Fisher's exact test showed no significant association between FBS, HbA1C, fructosamine and the improvement in cardiac MIBG uptake. The only significant association was observed between the serial change in H/M and the BS-control method (insulin therapy). Within the neurological parameters, a significant association was noted between the serial changes in H/M and CV(R-R). CONCLUSION: Although BS control was likely to be an important factor, it did not always ameliorate cardiac MIBG uptake. Based on the significant association between the BS-control method (insulin therapy) and MIBG uptake change, the severity of diabetes mellitus was likely to be a more influential factor. It was suggested that cardiac MIBG uptake could improve within the mild stage if controlled by diet therapy or an oral hypoglycemic agent in NIDDM.

3-Iodobenzylguanidine↗

PubMedDate not supplied

Prognostic value of cardiac I-123 metaiodobenzylguanidine imaging in patients with non-insulin-dependent diabetes mellitus.

BACKGROUND: 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy is a useful tool for diagnosing cardiac autonomic neuropathy (CAN) in non-insulin-dependent diabetes mellitus (NIDDM). However, the long-term prognostic value for cardiac events or mortality in NIDDM has not been clarified. METHODS AND RESULTS: We investigated the long-term prognostic value of cardiac MIBG imaging for both cardiac event and mortality owing to a variety of causes of death in NIDDM. 144 NIDDM patients were analyzed retrospectively with the end-points of a cardiac event and various causes of mortality. The heart-to-mediastinum uptake ratio on the delayed image (H/M [d]) was obtained from anterior planar imaging. The mean follow-up period was 7.2+/-3.2 years. Seventeen patients had a cardiac event onset and 7 patients died during observation. During the same observation course, 16 patients died, including some who died of cardiac event. Both multivariate and univariate analyses revealed that decreased H/M (d) (<1.7) was the independent predictor of long-term mortality for a variety of causes of death. Although the value of H/M (d) was not a significant prognostic factor for predicting a cardiac event, CAN, diagnosed by a combination of H/M (d) and coefficient variance of RR interval, was an independent predictor for the cardiac event in NIDDM. CONCLUSION: MIBG myocardial scintigraphy was useful for predicting cardiac events and long-term mortality in NIDDM.

3-Iodobenzylguanidine↗