Spontaneous Celiac and Splenic Artery Dissection.

Dissection of the splanchnic artery unrelated to an aortic lesion is extremely rare. We describe a patient with dissection of the celiac and splenic arteries causing splenic circulatory impairment. A 55-year-old Japanese man was referred to our hospital for left back pain that suddenly occurred 3 days previously and spread to the left flank. He had complicated sleep apnea syndrome well controlled with continuous positive airway pressure, and had been prophylactically taking aspirin (100 mg/day) because of asymptomatic cerebral lacunar infarcts. Contrast-enhanced computed tomography (CT) in the arterial phase revealed dissection from the celiac root extending to the entire splenic artery, the caliber of which was irregularly narrowed, causing malperfusion in the spleen. Because of hemodynamic stability and lack of impending sequelae, the patient was carefully observed with rest, strict blood pressure control, and aspirin administration. One month later, CT revealed restoration of the caliber of the dissected arteries and regression of the organizing false lumen, which confirmed the patient's recovery. Despite the extreme rarity or nonspecific symptoms, splanchnic artery dissection should be considered a potentially life-threatening emergency. This case supports the possible benefit of starting antithrombotic treatment early to prevent thrombotic sequelae such as organ infarction and aneurysmal formation.

Diagnostic Performance of Artificial Neural Network for Detecting Ischemia in Myocardial Perfusion Imaging.

BACKGROUND: The purpose of this study was to apply an artificial neural network (ANN) in patients with coronary artery disease (CAD) and to characterize its diagnostic ability compared with conventional visual and quantitative methods in myocardial perfusion imaging (MPI). METHODS AND RESULTS: A total of 106 patients with CAD were studied with MPI, including multiple vessel disease (49%), history of myocardial infarction (27%) and coronary intervention (30%). The ANN detected abnormal areas with a probability of stress defect and ischemia. The consensus diagnosis based on expert interpretation and coronary stenosis was used as the gold standard. The left ventricular ANN value was higher in the stress-defect group than in the no-defect group (0.92±0.11 vs. 0.25±0.32, P<0.0001) and higher in the ischemia group than in the no-ischemia group (0.70±0.40 vs. 0.004±0.032, P<0.0001). Receiver-operating characteristics curve analysis showed comparable diagnostic accuracy between ANN and the scoring methods (0.971 vs. 0.980 for stress defect, and 0.882 vs. 0.937 for ischemia, both P=NS). The relationship between the ANN and defect scores was non-linear, with the ANN rapidly increased in ranges of summed stress score of 2-7 and summed defect score of 2-4. CONCLUSIONS: Although the diagnostic ability of ANN was similar to that of conventional scoring methods, the ANN could provide a different viewpoint for judging abnormality, and thus is a promising method for evaluating abnormality in MPI.

Serial changes in glucose-loaded 18F-fluoro-2-deoxyglucose positron emission tomography, 99mTc-tetrofosmin and 123I-beta-methyl-p-iodophenyl-penta-decanoic acid myocardial single-photon emission computed tomography images in patients with anterior acute myocardial infarction.

BACKGROUND: (18)F-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) is assumed to be the most useful method for evaluating the viability of the myocardium. However, there are few reports regarding serial changes in (18)F-FDG-PET images of acute myocardial infarction (AMI). We evaluated serial changes in glucose-loaded (18)F-FDG-PET, (123)I-ß-methyl-p-iodophenyl-penta-decanoic acid (BMIPP) single-photon emission computed tomography (SPECT) and (99m)Tc-Tetrofosmin (TF) gated SPECT images in patients with AMI. METHODS AND RESULTS: We enrolled 7 consecutive patients with first anterior AMI who successfully underwent percutaneous coronary intervention (PCI). (18)F-FDG-PET images were obtained in the acute, subacute, chronic, mid-term and long-term phases. (123)I-BMIPP and (99m)Tc-TF SPECT images were obtained in the subacute, chronic, mid-term and long-term phases. We determined the total defect score (TDS) for each image. The TDS of the glucose-loaded (18)F-FDG-PET, (123)I-BMIPP and( 99m)Tc-TF SPECT images indicated significant serial decrease (P<0.001). Comparing these images, the TDS of the glucose-loaded (18)F-FDG-PET images was larger than that of the (123)I-BMIPP and (99m)Tc-TF SPECT images, and the TDS indicated (18)F-FDG-PET>(123)I-BMIPP>(99m)Tc-TF in all phases. CONCLUSIONS: The defect areas of glucose-loaded (18)F-FDG-PET images were significantly larger than those of (123)I-BMIPP and( 99m)Tc-TF SPECT images during 9 months follow-up of patients with successful PCI for anterior AMI. Additionally, the impairment of glucose metabolism was prolonged.

Quantitative regional blood flow measurements in exercising leg skeletal muscle based on 99mTc-pertechnetate clearance.

BACKGROUND AND AIM: Skeletal muscle blood flow (SMBF) is a crucial indicator of impaired peripheral circulation. Although 133Xe has long been used for estimation of regional SMBF, its lipophilic and volatile nature hampers precise measurement. Therefore, we established an improved method based on 99mTc-pertechnetate ion (99mTcO-4) clearance. METHODS: Ten healthy male volunteers including five rugby players and five non-athletes (each group aged 25-35 years) received injection of 99mTcO-4 into the bilateral tibialis anterior muscles and gastrocnemius muscles (GCMs). The radioactivity of 99mTcO-4 before, during, and after toe-up or treadmill exercise was traced using a gamma-camera. Regional SMBF in absolute values (in ml/min/100 g muscle) was then calculated based on the half-time obtained from the time-activity curve. RESULTS: In both the groups, SMBF in tibialis anterior muscle changed similarly with values at the same levels. In contrast, SMBF in GCM showed marked difference between the two groups: in rugby players, SMBF in GCM returned to the baseline level (6.5+/-1.7, n=10) immediately after treadmill exercise, whereas that in non-athletes remained high (16.2+/-3.2, n=10). CONCLUSION: Regional SMBF measured by 99mTcO-4 clearance can indicate effectiveness of exercise training, and would be a diagnostic tool and prognostic indicator for use in patients with impaired peripheral circulation.

Limitations of (99m)Tc tetrofosmin in assessing reversal effects of verapamil on the function of multi-drug resistance associated protein 1.

BACKGROUND: Previous reports have demonstrated the feasibility of scintigraphic assessment of the multi-drug resistance (MDR) of tumours caused by ATP binding cassette (ABC) transporters by using Tc cationic tracers such as Tc tetrofosmin (TF). Furthermore, the potential of these tracers for evaluating the effects of reversal agents for MDR has been documented. However, most reversal agents simultaneously affect cationic ion transporters related to tracer accumulation in tumours. METHODS: The uptake of Tc-TF was examined in the MCF7/WT cell line, a wild-type breast cancer cell line that does not exhibit MDR, and its subclonal etoposide resistant cell line MCF7/VP, which expresses high levels of MRP1, one of the multi-drug resistance associated proteins (MRPs), in the presence of increasing concentrations of verapamil, a classical MDR modulator. In the absence of verapamil, MCF7/VP cells showed significantly lower Tc-TF uptake than did MCF7/WT cells, indicating that Tc-TF is a substrate for MRP1. The presence of verapamil enhanced the uptake of Tc-TF in MCF7/VP cells. On the other hand, verapamil also increased tracer uptake in MCF7/WT cells, which was readily appreciated when the uptake values were corrected by viable cell numbers: an approximately 100% increase of Tc-TF uptake was observed in comparison with that in the absence of verapamil in viable MCF7/WT cells whereas a 100-200% increase occurred in viable MCF7/VP cells. In addition, verapamil prolonged the retention of radioactivity in both MCF7/WT cells and MCF7/VP cells. CONCLUSION: These results suggest that cellular functions other than MRP1 function, probably cationic ion transporters, are simultaneously and significantly involved in the verapamil induced changes of cellular uptake of Tc-TF. Tc-TF scintigraphy may overestimate the reversal effects of modulators on chemoresistance caused by MRP1 when the modulators simultaneously affect ion transporters.

Voluntary medication error reporting program in a Japanese national university hospital.

BACKGROUND: In Japan, as in other countries, medical accidents arising from human error can seriously damage public confidence in medical services, as well as being intrinsically undesirable. OBJECTIVE: Errors voluntarily reported by the healthcare practitioners in our institution (Kanazawa University Hospital) were considered to assess the contributory factors by using the accumulated error database in the hospital information system. METHODS: Medical errors in our institution during the period from July 1, 2000, to June 30, 2002, were counted using the error reporting system database and were classified. RESULTS: The number of errors reported during the investigation period was 1378, of which 78% were reported by nursing staff. Medication errors involving administration of injectable or oral drugs to inpatients, dispensing, and prescription accounted for about 50% of that number. Among dispensing errors, 53% were detected by patients or their families and 36% by nurses. CONCLUSIONS: The best method of error prevention is to learn from previous errors. For this purpose, the error reporting program is effective. In patient safety management, it is important to take into account the potential risks of future errors, as well as to capture information about errors that have already happened. For safety management, adoption of appropriate information technology (e.g., implementation of a prescription order entry system) is effective in reducing medication errors. However, it is important to note that serious errors can also arise in computer-based systems.

Reduction of 99mTc-sestamibi and 99mTc-tetrofosmin uptake in MRP-expressing breast cancer cells under hypoxic conditions is independent of MRP function.

Hypoxia reduces the uptake of technetium-99m sestamibi (MIBI) in human cancer cell lines. In the current investigation, we attempted to identify the relationship between hypoxia-induced alteration of (99m)Tc-MIBI accumulation and expression of multi-drug resistance-associated protein (MRP) in the MCF7/WT breast cancer cell line and its subclonal cell line, MCF7/VP, which expresses high levels of MRP1. A second cationic compound, (99m)Tc-tetrofosmin (TF), was also examined. Cellular uptake of (99m)Tc-MIBI and (99m)Tc-TF was significantly higher in parental MCF7/WT cells than in MCF7/VP cells. Hypoxic conditions generated with a mixture of 95% N(2) and 5% CO(2) reduced cellular uptake of the two tracers in both parental MCF7/WT cells and MRP1-expressing MCF7/VP cells. Cell binding assay with iodine-125-labelled anti-MRP1 antibody demonstrated its specific binding to MCF7/VP cells. Hypoxia did not affect the amount of antibody bound to MCF7/VP cells. These results indicate that hypoxia-induced reduction of tracer uptake in tumour cells is a phenomenon independent of MRP function.

Intraperitoneal radioimmunotherapy in treating peritoneal carcinomatosis of colon cancer in mice compared with systemic radioimmunotherapy.

Peritoneal spread is one of major causes of mortality in colorectal cancer patients. In the current investigation, the efficacy of radioimmunotherapy (RIT) with i.p. administration of an anti-colorectal cancer IgG1, 131I-A7, was compared to that with i.v. administration in BALB/c female mice bearing peritoneal nodules of LS180 human colon cancer cells, at the same toxicity level. Distribution of either i.p. or i.v. administered 131I-A7 and i.p. administered irrelevant 131I-HPMS-1 was assessed. Based on the results of toxicity determination at increments of 2 MBq and estimated dosimetry, an i.p. dose of 11 MBq and an i.v. dose of 9 MBq were chosen for treatment. Mice were monitored for long-term survival: untreated mice (n = 11), mice undergoing i.p. RIT with 131I-A7 (n = 11), mice undergoing i.v. RIT with 131I-A7 (n = 11) and mice undergoing non-specific i.p. RIT with 131I-HPMS-1 (n = 5). Intraperitoneal injection of 131I-A7 produced faster and greater tumor accumulation than i.v. injection: 34.2 +/- 16.5% of the injected dose per g (% ID/g) and 11.1 +/- 3.6% ID/g at 2 h, respectively (P < 0.0001). Consequently, cumulative radioactivity in tumors was 1.73-fold higher with i.p. injection. 131I-HPMS-1 did not show specific accumulation. Non-specific RIT with 131I-HPMS-1 (mean survival, 26.0 +/- 2.5 days) did not affect the survival as compared to no treatment (26.7 +/- 1.9 days). Intravenous RIT with 131I-A7 prolonged the survival of mice to 32.8 +/- 1.8 days (P < 0.01). Intraperitoneal RIT with 131I-A7 improved the survival more significantly and attained cure in 2 of 11 mice (P < 0.05 vs. i.v. RIT). In conclusion, i.p. RIT is more beneficial in treating peritoneal carcinomatosis of colon cancer than i.v. RIT in a murine model.

Local delivery of (131)I-MIBG to treat peritoneal neuroblastoma.

Internal radiotherapy involving systemic administration of iodine-131 metaiodobenzylguanidine ((131)I-MIBG) in neural crest tumours such as neuroblastoma has shown considerable success. Although peritoneal seeding of neuroblastoma occurs less often than metastases to organs such as the liver, no effective treatments exist in this clinical setting. Previous reports have demonstrated the effectiveness of peritoneal application of chemotherapeutic drugs or radiolabelled monoclonal antibodies in several kinds of carcinomas. Local delivery of (131)I-MIBG should produce more favourable dosimetry in comparison with its systemic administration in the treatment of peritoneal neuroblastoma. In the current investigation, a peritoneal model of neuroblastoma was established in Balb/c nu/nu mice by i.p. injection of SK-N-SH neuroblastoma cells. Two weeks after cell inoculation, comparative biodistribution studies were performed following i.v. or i.p. administration of (131)I-MIBG. Mice were treated with 55.5 MBq of (131)I-MIBG administered either i.v. or i.p. at 2 weeks. Intraperitoneal injection of (131)I-MIBG produced significantly higher tumour accumulation than did i.v. injection ( P<0.01). Therapeutic ratios of i.p. injection were 4- to 14-fold higher than those of i.v. injection. Radiotherapy with i.v. administered (131)I-MIBG failed to improve the survival of mice; mean survival of untreated mice and mice treated with i.v. administration of (131)I-MIBG was 59.3+/-3.9 days and 60.6+/-2.8 days, respectively. On the other hand, radiotherapy delivered via i.p. administration of (131)I-MIBG prolonged survival of mice to 94.7+/-17.5 days ( P<0.02 vs untreated controls and mice treated with i.v. (131)I-MIBG therapy). Radiation doses absorbed by tumours at 55.5 MBq of (131)I-MIBG were estimated to be 4,140 cGy with i.p. injection and 450 cGy with i.v. injection. These results indicate the benefits of locoregional delivery of (131)I-MIBG in the treatment of peritoneal neuroblastoma.

Cooperative effect of radioimmunotherapy and antiangiogenic therapy with thalidomide in human cancer xenografts.

UNLABELLED: Antiangiogenic therapy may prolong the dormancy of cancer lesions. Moreover, radioimmunotherapy (RIT) may eradicate this population of cells. This study dealt with determining the benefits associated with the combined usefulness of these 2 therapies with respect to inhibition of tumor growth. METHODS: Antiangiogenic therapy using oral thalidomide (daily dose, 200 mg/kg) and RIT involving a single intravenous injection (4.63 MBq (131)I-A7, an IgG1 murine monoclonal antibody) were conducted in mice bearing LS180 human colon cancer xenografts. RIT with an irrelevant IgG1, HPMS-1, was also performed as a control. Antiangiogenesis of thalidomide was investigated by immunohistochemical analysis of tumor sections. RESULTS: Antiangiogenic therapy and RIT with (131)I-A7 significantly suppressed the growth of xenografts. This combination produced more efficient tumor growth inhibition than did the monotherapy (P < 0.005). RIT using (131)I-HPMS-1 was far less effective than (131)I-A7, even when combined with thalidomide administration. Immunohistochemistry revealed a decrease in the microvessel number within tumors treated with thalidomide (P < 0.0001). Combined therapy further reduced the microvessel number (P < 0.01 vs. thalidomide monotherapy). CONCLUSION: The combination of RIT and thalidomide antiangiogenic therapy produces a better response of tumors than does monotherapy. Acting in concert, antiangiogenic therapy may prolong the dormancy of cancer lesions and RIT may eradicate this population of cells.

Hypoxia-induced alteration of tracer accumulation in cultured cancer cells and xenografts in mice: implications for pre-therapeutic prediction of treatment outcomes with (99m)Tc-sestamibi, (201)Tl chloride and (99m)Tc-HL91.

Weak visualization of tumours in pre-therapeutic scintigrams with technetium-99m sestamibi (MIBI) is likely a predictive sign of unfavourable tumour response to radiotherapy and chemotherapy. However, factors relating to this scintigraphic finding are not well understood. The presence of hypoxic tumour cells is one of the major reasons for therapeutic failure; consequently, we attempted to determine whether oxygenation status affects (99m)Tc-MIBI accumulation in tumour cells. LS180 human colon cancer and T24 human bladder cancer cells were incubated in air or N(2) gas at 37 degrees C. Cellular uptake of (99m)Tc-MIBI was subsequently determined at 15, 60 and 120 min. Uptake of thallium-201 chloride was also assessed. Uptake of (99m)Tc-HL91 was assessed as a hypoxic marker. Accumulation of the tracers in LS180 xenografts was observed in mice treated with 5 mg/kg hydralazine and compared with that in untreated mice. pO(2) in the medium and tumours was measured with O(2) microelectrodes. N(2) gas flow gradually reduced pO(2) in the cell suspension to 1-2 mmHg in 60 min. Cellular uptake of (99m)Tc-MIBI in LS180 cells decreased by approximately 30% in N(2) gas in comparison to that in air throughout the study. Hypoxia had a more prominent influence on (201)Tl uptake, which displayed a reduction of approximately 60% in N(2) gas at 120 min, than on (99m)Tc-MIBI uptake. On the other hand, N(2) gas induced an increase of 170% in (99m)Tc-HL91 uptake at 120 min, indicating the hypoxic condition of cells. The results of in vitro assays employing the T24 cell line were similar to those obtained with the LS180 cell line. Hydralazine treatment markedly reduced (99m)Tc-MIBI and (201)Tl accumulation in LS180 xenografts; moreover, intratumoural pO(2) decreased from 14.5 +/- 6.6 mmHg to 7.6 +/- 6.2 mmHg. (99m)Tc-HL91 accumulation in xenografts was markedly increased by hydralazine. In conclusion, hypoxia reduced accumulation of (99m)Tc-MIBI and (201)Tl in tumour cells. Accordingly, hypoxia may be an important factor in terms of the interpretation of scintigraphic findings obtained with these tracers for pre-therapeutic prediction of tumour response to treatment. Furthermore, the enhanced (99m)Tc-HL91 accumulation in hypoxic tumour cells indicates the usefulness of this tracer in this regard.

[The effects of the revision of medical repayment standards on pharmaceutical counseling services and revenue at pediatrics of Kanazawa University Hospital].

This paper analyzes the effects of the revision of medical repayment standards in April 2000 on pharmaceutical care and economics. The total number of sessions of counseling that can be claimed in 1 month has apparently improved at the Pediatrics Department of Kanazawa University Hospital. On the other hand, actual repayment for said services has not necessarily risen accordingly. This was shown by adopting new calculation modalities for actual claims before revision. We believe that this discrepancy occurs because the charge for each service has decreased from 480 points to 350 points, while maximum number of effective claims per month has risen from twice to four times.

Electrocardiographic gated (99m)Tc-MIBI SPECT for functional assessment of patients after coronary artery bypass surgery: comparison of wall thickening and wall motion analysis.

UNLABELLED: Abnormal septal motion after coronary artery bypass graft surgery (CABG) is a common finding. This study was undertaken to investigate the change in various global and regional ventricular function parameters measured by gated myocardial perfusion SPECT after surgery and to determine which quantitative parameter of WT and WM is more appropriate for the evaluation of regional cardiac function, especially in the septum of patients with CABG. METHODS: Before and 3 to 5 wk after CABG (all patients underwent at least 1 bypass grafting to the left anterior descending coronary artery), 35 patients (28 men, 7 women) underwent gated SPECT using (99m)Tc-methoxyisobutylisonitrile. Quantitative global and regional ventricular functional analysis was performed using quantitative gated SPECT software. RESULTS: Global ejection fraction did not change (59.3% +/- 16.0% to 60.5% +/- 14.5%, P = 0.24). However, end-diastolic and end-systolic volumes lessened significantly after CABG (81.4 +/- 37.3 mL to 68.9 +/- 28.9 mL, P < 0.0001, and 38.1 +/- 33.1 mL to 30.4 +/- 23.0 mL, P < 0.005, respectively). As global function parameters, the changes in both total WM (r = 0.88) and WT (r = 0.86) correlated well with the change in ejection fraction after surgery. Segmental analysis showed a significant postoperative increase in relative tracer uptake in the anterior, anteroseptal, inferoseptal, and inferior walls and in the apex. Segmental wall motion (WM) deteriorated in the anteroseptal, inferoseptal, and mid anterior walls. On the other hand, anterolateral, inferolateral, and inferior WM increased. As a whole, these WM changes showed a reduction in septal motion associated with a concomitant increase in lateral motion after surgery. Segmental wall thickening, however, did not decrease in septal areas and did not increase in the lateral wall and correlated with percentage tracer uptake (r = 0.69) better than WM did (r = 0.30) after CABG. CONCLUSION: In patients with CABG, postoperative WM analysis by gated SPECT underestimated septal motion and overestimated lateral motion because of exaggerated systolic anteromedial cardiac translation. Therefore, wall thickening analysis would be recommended for the evaluation of postoperative cardiac function.

Radioimmunotherapy with 186Re-labeled monoclonal antibody to treat liver metastases of colon cancer cells in nude mice.

The efficacy of radioimmunotherapy (RIT) in the treatment of minimal disease has been previously shown, despite the limitation of beta-emitters suggested by a mathematical model. In the present study, the efficacy of RIT with an anti-colorectal cancer IgG1 A7 conjugated with 186Re was examined in a liver metastasis model established by intrasplenic inoculation of human colon cancer cells. In this model, small metastases of less than 1 mm in diameter can be observed 1 week after cell inoculation. Metastases attain a diameter of several millimeters at 2 weeks. 186Re-A7 accumulated exclusively in metastases, displaying a value of 24.1 +/- 8.7% ID/g 2 days after the injection. 186Re-A7 accumulation in liver metastases increased with decreasing size. RIT with 7 MBq 186Re-A7 at 2 weeks significantly suppressed the growth of metastases; weight of metastases 4 weeks after cell inoculation was 5.96 +/- 0.87 g in nontreated control mice and 1.25 +/- 0.75 g in mice receiving 186Re-A7 RIT (p < 0.0001). RIT at 1 week more effectively inhibited metastatic growth to 0.08 +/- 0.05 g (p < 0.002 vs. RIT at 2 weeks). RIT with a class-matched irrelevant MAb 186Re-HPMS-1 at 1 week after cell inoculation somewhat suppressed metastatic growth, 3.39 +/- 0.25 g at 4 weeks, as compared with the control; however, 186Re-HPMS-1 RIT was far less effective than 186Re-A7 RIT (p < 0.0001). These results support the use of RIT with 186Re-MAb in an adjuvant setting in cases involving minimal disease. Factors such as higher and homogeneous MAb accumulation in small nodules, better perfusion, and subsequent better oxygenation likely compensate for the loss of beta radiation outside small metastases.