Reduced 125I-meta-iodobenzylguanidine uptake and norepinephrine transporter density in the hearts of mice with MPTP-induced parkinsonism

Uptake of (123)I-meta-iodobenzylguanidine ((123)I-MIBG) is markedly reduced in the hearts of patients with Parkinson's disease. Although the mechanism of this reduction is unclear, (12)(5)I-MIBG uptake is similarly reduced in the hearts of mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydroxypyridine (MPTP)-induced parkinsonism. Three groups of ten 15-week-old C57BL6 mice received intraperitoneal injections of (1) saline (control), (2) 10 mg/kg MPTP or (3) 40 mg/kg MPTP. After 0.185 MBq of (125)I-MIBG was injected, the percent injected dose of (125)I-MIBG per gram of tissue (%ID/g) was determined and cardiac concentrations of norepinephrine were measured. Cardiac concentrations of norepinephrine transporter (NET) were measured in three groups of twenty 15-week-old C57BL6 mice receiving these same treatments. The %ID/g in mice receiving 10 or 40 mg/kg MPTP (5.7 +/- 1.1 and 4.4 +/- 1.2%/g) was significantly lower than that in control mice (11.3 +/- 2.2%/g; P < .00001 and P < .0000001, respectively). The norepinephrine concentration in mice receiving 10 or 40 mg/kg MPTP (7.86 +/- 0.67 x 10(5) and 7.50 +/- 0.89 x 10(5) pg/wet g) was significantly lower than that in control mice (9.21 +/- 0.97 x 10(5) pg/wet g; P < .01 and P < .001, respectively). The NET density in mice receiving 10 or 40 mg/kg MPTP (81 +/- 12, 61 +/- 7 fmol/mg protein) was significantly lower than that in control mice (126 +/- 7 fmol/mg protein; P < .000001 and P < .0000001, respectively). The %ID/g of (125)I-MIBG and NET density decreased as the dose of MPTP increased. This study clearly shows that reduced cardiac (12)(5)I-MIBG uptake in mice with MPTP-induced parkinsonism is closely related to the reduced NET density in postganglionic cardiac sympathetic nerve terminals.     

Impaired myocardial 123I-metaiodobenzylguanidine uptake in Lewy body disease: comparison between dementia with Lewy bodies and Parkinson's disease

BACKGROUND: Iodine-123-labeled metaiodobenzylguanidine (123I-MIBG) myocardial scintigraphy has been used to evaluate cardiac sympathetic denervation in Lewy body disease (LBD) including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Patients with LBD had marked reductions in cardiac MIBG accumulation, indicative of severe impairment of the cardiac sympathetic nervous systems. However, the differences in scintigraphy between DLB and PD have not been determined. OBJECTIVE: To compare cardiac sympathetic function in early disease stage measured with 123I-MIBG scintigraphy between DLB and PD. METHODS: 123I-MIBG myocardial scintigraphy was performed in 22 patients with early-stage DLB, 41 patients with early idiopathic PD and 15 normal control subjects who were matched for age and disease duration. The heart-to-mediastinum (H/M) ratio was calculated. RESULTS: 123I-MIBG uptake of the myocardium was significantly lower in patients with early DLB than in controls. The mean value of H/M ratio in patients with DLB was significantly lower than those in patients with PD, independent of the Hoehn and Yahr stage. CONCLUSIONS: Our findings suggest that cardiac sympathetic function in DLB is severely impaired even in the early disease stage.     

Investigation of the present management status of calibration source based on the law concerning prevention of radiation hazards due to radioisotopes

An amendment concerning the enforcement of the law on the prevention of radiation hazards due to radioisotopes, etc., and the medical service law enforcement regulations were promulgated on June 1, 2005. This amendment concerned international basic safety standards and the sealing of radiation sources. Sealed radiation sources < or =3.7 MBq, which had been excluded from regulation, were newly included as an object of regulation. Investigation of the SPECT system instituted in hospitals indicated that almost all institutions adhere to the new amendment, and the calibration source, the checking source, etc., corresponding to this amendment were maintained appropriately. Any institutions planning to return sealed radioisotopes should refer to this report.     

Total arch replacement for a distal aortic arch aneurysm with right aortic arch

Right-sided aortic arch accompanied by an aberrant origin of the left subclavian artery is rare and seen in 0.05% approximately 0.1% of the population. A 73-year-old woman with this anomaly was admitted to our institution because of the enlargement of the distal aortic arch aneurysm. She also had mild dysphagia. The size of the aneurysm was 70 mm in diameter and she underwent total arch replacement using selective cerebral perfusion through a median sternotomy. Additional right thoracotomy was not required and four cervical vessels were reconstructed. The postoperative course was uneventful. This case report shows median sternotomy alone may provide sufficient access for this pathology.     

Perioperative management for cesarean section in a patient with pulmonary thromboembolism due to deep venous thrombosis

It has been estimated in Japan that Western-life style increases maternal mortality because of pulmonary thromboembolism (PTE). We report a 29-year-old primipara who suffered PTE due to deep venous thrombosis (DVT) in her 29th weeks' gestation. Except for slight tachypnea, she was relatively stable. Anticoagulation with heparin was started immediately. The retrievable inferior vena cava filter (IVC-F) was inserted. Four hours before surgery with discontinuation of heparin, the cesarean section was performed under general anesthesia. We used transesophageal echocardiography, a pulmonary artery catheter and end tidal CO2 monitoring for early detection and rapid management of recurrent PTE. She had no trouble during operation and her baby was born without serious symptoms. After recovery from anesthesia, she was admitted to the intensive care unit. Heparin was restarted after confirmation of hemostasis. On the 3rd postoperative day, we started thrombolytic therapy with urokinase which was tapered off during a week. Heparin was switched to warfarine gradually. On the 10th postoperative day, IVC-F could not be removed because of remaining DVT. She was discharged on daily warfarine. We experienced the perioperative management for cesarean section at 29 weeks' gestation following PTE due to DVT.     

A screening test for the prediction of Dravet syndrome before one year of age

PURPOSE: Our aim was to develop a screening test to predict Dravet syndrome before the first birthday based on the clinical characteristics of infants and the SCN1A mutation analysis. METHODS: Ninety-six patients who experienced febrile seizures before the age of one were enrolled. The patients were divided into two groups-the Dravet syndrome group (n = 46) and the non-Dravet syndrome group (n = 50). We compared the clinical characteristics before one year of age of the two groups. We analyzed all coding exons of the SCN1A gene by the direct sequencing method. Scores from 0 to 3 were assigned to each risk factor based on the odds ratio and p-value. RESULTS: An age of onset of febrile seizure or= 5, and prolonged seizures lasting more than 10 min. were regarded as significant risk factors for Dravet syndrome. Other factors highly predictive of this syndrome were hemiconvulsions, partial seizures, myoclonic seizures, and hot water-induced seizures. A total clinical score of six or above was the cutoff value indicating a high risk of Dravet syndrome. SCN1A missense and truncated mutations were detected significantly more often in the Dravet syndrome group than in the non-Dravet syndrome group. DISCUSSION: This simple screening test was designed to be used by general pediatricians. It could help to predict Dravet syndrome before one year of age. If the sum of the clinical risk score is >or= 6, then the performance of an SCN1A mutation analysis is recommended.     

New technique for knee flexion contracture with patella infera using patellar tendon reconstruction combined with anterior capsular shift: a case report

A 24-year-old male presented with an open fracture of the left patella (Gustilo–Anderson grade III-A) and fracture of the left femoral lateral condyle, and subsequent patella alta suggesting rupture of the left patellar tendon. This initial injury was treated 6 months earlier in another hospital. He was referred because of limited knee motion and radiographs showed severe patella infera. By means of a combination of a contralateral BTB graft and soft tissue repair named anterior capsular shift, the knee contracture with patella infera was resolved successfully. All devices used in this article were approved by Organization of the Ministry of Health, Labourand Welfare in Japan.     

Repeated treatment with cannabidiol but not Delta9-tetrahydrocannabinol has a neuroprotective effect without the development of tolerance

Both Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and cannabidiol are known to have a neuroprotective effect against cerebral ischemia. We examined whether repeated treatment with both drugs led to tolerance of their neuroprotective effects in mice subjected to 4h-middle cerebral artery (MCA) occlusion. The neuroprotective effect of Delta(9)-THC but not cannabidiol was inhibited by SR141716, cannabinoid CB(1) receptor antagonist. Fourteen-day repeated treatment with Delta(9)-THC, but not cannabidiol, led to tolerance of the neuroprotective and hypothermic effects. In addition, repeated treatment with Delta(9)-THC reversed the increase in cerebral blood flow (CBF), while cannabidiol did not reverse that effect. Repeated treatment with Delta(9)-THC caused CB(1) receptor desensitization and down-regulation in MCA occluded mice. On the contrary, cannabidiol did not influence these effects. Moreover, the neuroprotective effect and an increase in CBF induced by repeated treatment with cannabidiol were in part inhibited by WAY100135, serotonin 5-HT(1A) receptor antagonist. Cannabidiol exhibited stronger antioxidative power than Delta(9)-THC in an in vitro study using the 1,1-diphenyl-2-picryhydrazyl (DPPH) radical. Thus, cannabidiol is a potent antioxidant agent without developing tolerance to its neuroprotective effect, acting through a CB(1) receptor-independent mechanism. It is to be hoped that cannabidiol will have a palliative action and open new therapeutic possibilities for treating cerebrovascular disorders.