RESUMO
Cold fingers is complaint of many people. To independently assess actual finger temperature, this paper uses prototype sensors to capture blood vessel width and blood flow rates. We verify their feasibility for future home healthcare use along with far infrared camera outputs. We elucidate the impact of three remedies, massage, hot cocoa, and shoulder exercises, on 7 subjects.
Assuntos
Temperatura Corporal/fisiologia , Dedos/fisiologia , Processamento de Imagem Assistida por Computador/métodos , Monitorização Fisiológica/métodos , Processamento de Sinais Assistido por Computador , Termografia/métodos , HumanosRESUMO
We report on serial MRI findings of cerebral lesions in a 55-year-old man with severe Marchiafava-Bignami disease (MBD). The first MRI change on fluid-attenuated inversion recovery images was hyperintensity in the genu of the corpus callosum and in the frontoparietal cortex. Following this change, a splenial lesion appeared. The first MRI change in the genu of the corpus callosum was not associated with a change in diffusion on diffusion-weighted MRI imaging, suggesting a pathological change involving vasogenic edema. Development of cortical lesions in the initial stage confirms that cortical lesions result from the primary pathogenetic process induced by alcoholic intoxication and malnutrition in MBD.
RESUMO
We have developed a laser and focused ion beam (FIB) compound system to process an optical component device with an ultrafine precision minute surface structure and a micromedical device. This machine consists of an FIB and three types of lasers with an atomic force microscope. This system can fabricate decamicrometer area by laser and submicrometer area by FIB at one chuck. When processing the press mold die of a microlens array (10x10) in a glasslike carbon with a femtosecond laser, a diameter of 3.2 microm and depth of 0.43 microm are obtained. However, the surface roughness is more than Rz=0.5 microm. After this process, we finished this surface with the use of the FIB. As a result, the surface roughness is less than Rz=0.05 microm.
Assuntos
Lasers , Dispositivos Ópticos , Carbono/química , Microscopia de Força Atômica , Propriedades de Superfície , Fatores de Tempo , Raios UltravioletaRESUMO
In this report, we present CT and MRI findings of a case of a schwannoma that developed in the floor of the oral cavity. A 49-year-old woman visited our hospital with a painless swelling in the oral floor. CT and MRI revealed a well circumscribed oval mass in the sublingual space, which showed cystic degeneration in most of the lesion. In addition, a thickened wall that strongly enhanced after injection of contrast medium and formation of fluid level were observed in the mass. The mass was removed and was histopathologically diagnosed as schwannoma. Only a few cases of schwannoma in the oral floor have been reported. However, when the characteristic findings are observed on CT and MRI, schwannoma should be added to the differential diagnosis.
Assuntos
Soalho Bucal/patologia , Neoplasias Bucais/diagnóstico , Neurilemoma/diagnóstico , Meios de Contraste , Diagnóstico Diferencial , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) has so far been reported almost exclusively from the USA and Europe. We carried out this study to define the clinical characteristics of this syndrome in Japanese patients. METHODS: Prospectively, we identified 13 Japanese patients with RS3PE (5 men and 8 women, age 72.7 +/- 11.8 years (mean +/- SD)) without underlying neoplasm. Their clinical features were summarized, pertinent laboratory data including serum/synovial interleukin-6 (IL-6) concentrations were obtained, and extensive radiologic studies using magnetic resonance imaging and 67gallium-citrate (67Ga) whole body scintigram were performed. RESULTS: All patients suffered from proximal arthralgia/myalgia in addition to typical distal symptoms of RS3PE, and all experienced systemic symptoms such as fever, malaise, and weight loss. In laboratory examinations, anemia and elevated inflammatory markers were often remarkable. Magnetic resonance imaging showed severe tenosynovitis of the hands. 67Ga-scintigram revealed radioisotope accumulation in both proximal and distal joints of the extremities. IL-6 activity was markedly elevated both in the serum (mean 82.4 +/- 62.1 (SD) pg/ml, normal range 0.157-2.94) and in the synovial fluid (mean 3350 +/- 633 (SD) pg/ml). CONCLUSION: Compared with cases reported previously from the USA/Europe, Japanese patients with RS3PE are characterized by more prominent systemic symptoms/signs associated with marked inflammatory responses including elevated IL-6 activity. All patients had proximal as well as distal synovitis which could be demonstrated by 67Ga-scintigram. These clinical features were very similar to those of polymyalgia rheumatica, suggesting that RS3PE and polymyalgia rheumatica are closely related disorders which may have a common pathogenesis.
Assuntos
Edema , Interleucina-6/metabolismo , Sinovite , Idoso , Idoso de 80 Anos ou mais , Edema/diagnóstico , Edema/tratamento farmacológico , Edema/metabolismo , Feminino , Radioisótopos de Gálio , Glucocorticoides/uso terapêutico , Mãos/patologia , Humanos , Japão , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Polimialgia Reumática/patologia , Prednisolona/uso terapêutico , Compostos Radiofarmacêuticos , Remissão Espontânea , Síndrome , Sinovite/diagnóstico , Sinovite/tratamento farmacológico , Sinovite/metabolismo , Tenossinovite/diagnóstico , Tenossinovite/tratamento farmacológico , Tenossinovite/metabolismoRESUMO
We investigated the potential of the wireless teleradiology system, using a Personal Handyphone System(PHS) and hand-held personal computer. To provide and interpret CT images, an internet web system was used. It took 5.5 seconds to transmit a single CT image of 28 KB. Therefore, about 2 minutes was required to brawse a series of brain examinations(20 CT images). Although transmission speed needs to be increased, our system makes it possible to perform imaging diagnosis anywhere and is especially useful in emergency situations.
Assuntos
Microcomputadores , Telerradiologia , Humanos , Telefone , Telerradiologia/normas , Tomografia Computadorizada por Raios XRESUMO
A 70-year-old man who had undergone a low anterior resection for primary rectal cancer 9 years before complained of anorexia, hemiplegia, and recurrent laryngeal nerve palsy. The anorexia was caused by duodenal stenosis due to swollen lymph nodes, the hemiplegia was caused by a metastatic brain tumor, and the recurrent laryngeal nerve palsy was caused by metastases of the cancer to the mediastinal space. Metastases were also found in the bilateral lungs, liver, ureter, and cervical vertebra. In choosing the anesthesia for the gastrojejunostomy to improve the malnutrition of this patient, we decided, on the basis of the patient's full stomach, malnutrition, hypovolemia, hemiplegia, cerebral compression, recurrent laryngeal nerve palsy, renal dysfunction, and respiratory dysfunction, to use thoracic epidural anesthesia rather than spinal anesthesia or general anesthesia. Thoracic epidural anesthesia could provide sufficient analgesia, and the operation was uneventful. In anesthetic management of an end-stage patient undergoing a palliative operation like this, we should consider the purpose of the operation, its complications, and further complications which may be induced by anesthesia in order to plan out an anesthetic regimen unlikely to lead to harmful events in perioperative period.
Assuntos
Anestesia Epidural/métodos , Gastrostomia , Hemiplegia/complicações , Jejunostomia , Nervo Laríngeo Recorrente , Paralisia das Pregas Vocais/complicações , Idoso , Humanos , Masculino , Distúrbios Nutricionais/complicações , Cuidados PaliativosRESUMO
We examined the properties of voltage-dependent Ca(2+) channels (VDCCs) mediating 1-methyl-4-phenylpyridinium (MPP(+))-evoked [3H]DA release from rat striatal slices. In some cases, the Ca(2+)-independent efflux of neurotransmitters is mediated by the high-affinity neurotransmitter-uptake systems. To determine whether such a mechanism might be involved in MPP(+)-evoked [3H]DA release. MPP(+) (1,10 and 100 microM) evoked the release of [3H]DA from rat striatal slices in a concentration-dependent manner. In the absence of Ca(2+), MPP(+) (10 and 100 microM)-evoked [3H]DA release was significantly decreased to approximately 50% of control (a physiological concentration of Ca(2+)). In the presence of Ca(2+), nomifensine (0.1,1 and 10 microM) dose-dependently and significantly inhibited the MPP(+)-evoked release of [3H]DA. Nomifensine (1 and 10 microM) also dose-dependently and significantly inhibited the MPP(+)-evoked release of [3H]DA under Ca(2+)-free conditions. MPP(+)-evoked [3H]DA release was partly inhibited by nicardipine (1 and 10 microM), an L-type Ca(2+) channel blocker. On the other hand, the N-type Ca(2+) channel blocker omega-conotoxin-GVIA (omega-CTx-GVIA) (1 and 3 microM) did not affect this release. omega-agatoxin-IVA (omega-Aga-IVA) at low concentrations (0.1 microM), which are sufficient to block P-type Ca(2+) channels alone, also had no effect. On the other hand, MPP(+)-evoked [3H]DA release was significantly decreased by high concentrations of omega-Aga-IVA (0.3 microM) that would inhibit Q-type Ca(2+) channels. In addition, application of the Q-type Ca(2+) channel blocker omega-conotoxin-MVIIC (omega-CTx-MVIIC) (0.3 and 1 microM) also significantly inhibited MPP(+)-evoked [3H]DA release. These results suggest that MPP(+)-evoked [3H]DA release from rat striatal slices is largely mediated by Q-type Ca(2+) channels, and the Ca(2+)-independent component is mediated by reversal of the DA transport system.
Assuntos
1-Metil-4-fenilpiridínio/farmacologia , Corpo Estriado/metabolismo , Dopamina/metabolismo , Animais , Transporte Biológico Ativo/fisiologia , Cálcio/fisiologia , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio/efeitos dos fármacos , Canais de Cálcio/fisiologia , Inibidores da Captação de Dopamina/farmacologia , Relação Dose-Resposta a Droga , Técnicas In Vitro , Masculino , Nomifensina/farmacologia , Ratos , Ratos WistarRESUMO
We gave total intravenous anesthesia to an over-100% hyper-obese patient using target-controlled infusion (TCI) of propofol and fentanyl. To keep him asleep, we maintained his BIS in a range of 40 to 60 by adjusting the target concentration of propofol. For the target concentration of fentanyl, we chose 2 ng.ml-1 at incision and 1.6 ng.ml-1 during the operation. At the patient's emergence from anesthesia, his estimated blood concentration of propofol was 1.51 micrograms.ml-1 and his BIS was 80. The relationship between BIS value and effect-site concentration of propofol was almost the same as that assessed in ordinary adults of a normal weight. We conclude that the estimated concentration of propofol is a good indicator of the effect of propofol and that TCI is a useful technique in obese patients as well as in ordinary adults.
Assuntos
Anestesia Intravenosa/métodos , Anestésicos Intravenosos , Fentanila , Obesidade Mórbida/complicações , Propofol , Adulto , Humanos , Infusões Intravenosas , Masculino , Neoplasias da Glândula Tireoide/cirurgia , TireoidectomiaRESUMO
The aims of this study were to identify monoamine transporters expressed in human glial cells, and to examine the regulation of their expression by stress-related growth factors. The expression of serotonin transporter mRNA was detected by reverse transcriptase-polymerase chain reaction in normal human astrocytes, whereas the dopamine transporter (DAT) and the norepinephrine transporter (NET) were not detected. The cDNA sequence of the "glial" serotonin transporter in astrocytes was consistent with that reported for the "neuronal" serotonin transporter (SERT). Moreover, we also demonstrated SERT expression in glial fibrillary acidic protein-positive cells by immunocytochemical staining in normal human astrocytes. Serotonin transporter gene expression was also detected in glioma-derived cell lines (A172, KG-1-C and KGK). Addition of basic fibroblast growth factor (bFGF) or epidermal growth factor (EGF) for 2 days increased serotonin transporter gene expression in astrocytes and JAR (human choriocarcinoma cell line). Basic fibroblast growth factor, but not epidermal growth factor, increased specific [3H]serotonin uptake in astrocytes in a time (1-4 days)- and concentration (20-100 ng/ml)-dependent manner. The expression of genes for basic fibroblast growth factor and epidermal growth factor receptors was detected in astrocytes. These findings suggest that the expression of the serotonin transporter in human glial cells is positively regulated by basic fibroblast growth factor.
Assuntos
Proteínas de Transporte/genética , Substâncias de Crescimento/farmacologia , Glicoproteínas de Membrana/genética , Proteínas de Membrana Transportadoras , Proteínas do Tecido Nervoso , Neuroglia/efeitos dos fármacos , Astrócitos/citologia , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Células Cultivadas , Relação Dose-Resposta a Droga , Fator de Crescimento Epidérmico/farmacologia , Fator 2 de Crescimento de Fibroblastos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Glioma/genética , Glioma/patologia , Humanos , Neuroglia/citologia , Neuroglia/metabolismo , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Serotonina/farmacocinética , Proteínas da Membrana Plasmática de Transporte de Serotonina , Fatores de Tempo , Células Tumorais CultivadasRESUMO
BACKGROUND: The International Child Care Practices Study (ICCPS) has collected descriptive data from 21 centres in 17 countries. In this report, data are presented on the infant sleeping environment with the main focus being sudden infant death syndrome (SIDS) risk factors (bedsharing and infant using a pillow) and protective factors (infant sharing a room with adult) that are not yet well established in the literature. METHODS: Using a standardised protocol, parents of infants were surveyed at birth by interview and at 3 months of age mainly by postal questionnaire. Centres were grouped according to geographic location. Also indicated was the level of SIDS awareness in the community, i.e. whether any campaigns or messages to "reduce the risks of SIDS" were available at the time of the survey. RESULTS: Birth interview data were available for 5488 individual families and 4656 (85%) returned questionnaires at 3 months. Rates of bedsharing varied considerably (2-88%) and it appeared to be more common in the samples with a lower awareness of SIDS, but not necessarily a high SIDS rate. Countries with higher rates of bedsharing appeared to have a greater proportion of infants bedsharing for a longer duration (>5 h). Rates of room sharing varied (58-100%) with some of the lowest rates noted in centres with a higher awareness of SIDS. Rates of pillow use ranged from 4% to 95%. CONCLUSIONS: It is likely that methods of bedsharing differ cross-culturally, and although further details were sought on different bedsharing practices, it was not possible to build up a composite picture of "typical" bedsharing practices in these different communities. These data highlight interesting patterns in child care in these diverse populations. Although these results should not be used to imply that any particular child care practice either increases or decreases the risk of SIDS, these findings should help to inject caution into the process of developing SIDS prevention campaigns for non-Western cultures.
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Saúde Global , Cuidado do Lactente/métodos , Relações Mãe-Filho/etnologia , Sono/fisiologia , Morte Súbita do Lactente/etnologia , Leitos , Comparação Transcultural , Humanos , Lactente , Recém-Nascido , Entrevistas como Assunto , Fatores de Risco , Morte Súbita do Lactente/prevenção & controle , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The amount of dehydroascorbic acid contained within total ascorbic acid (oxidized as well as non-oxidized forms) in plasma, hereafter referred to as the dehydroascorbic acid fraction, may be a measure of oxidative stress during haemodialysis. In the present study, we determined this fraction in chronic haemodialysis patients. METHODS: Using high performance liquid chromatography, dehydroascorbic acid and total ascorbic acid levels were measured in 80 maintenance haemodialysis patients for a period of > 2 years as well as in 49 controls, to examine a possible association of these compounds with clinical parameters and/or drugs taken by the patients. RESULTS: Dialysis patients who had an increased plasma urate level (P < 0.05) and had been taking allopurinol (P < 0.05) or NSAID (non-steroid anti-inflammatory drugs) (P < 0.01), and dialysis patients who were younger (< or = 55 years), as compared with older dialysis patients (P < 0.01), were found to have a lower dehydroascorbic acid fraction by multivariate analysis. Mean plasma dehydroascorbic acid levels and dehydroascorbic acid fractions were significantly lower in the younger haemodialysis patients (4.8 +/- 0.7 micromol/l and 28.4 +/- 3.9%) than in healthy younger controls (13.3 +/- 1.1 micromol/l and 41.1 +/- 1.8%) (P < 0.0001 and P < 0.01, respectively). Moreover, a correlation was found between plasma dehydroascorbic acid fraction and plasma lipid peroxide (r = 0.66, P < 0.01) in patients who had not been taking allopurinol and/or NSAID. CONCLUSION: We found that dehydroascorbic acid fraction was related to patients' age, plasma urate level and to taking allopurinol or NSAID. Dehydroascorbic acid fraction may be another indirect index of oxidative stress.
Assuntos
Ácido Desidroascórbico/sangue , Falência Renal Crônica/sangue , Falência Renal Crônica/terapia , Estresse Oxidativo , Diálise Renal , Envelhecimento/sangue , Alopurinol/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Antimetabólitos/uso terapêutico , Estudos de Casos e Controles , Feminino , Humanos , Peróxidos Lipídicos/sangue , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valores de Referência , Ácido Úrico/sangueRESUMO
We have previously identified 204 partial cDNA fragments (ADRG1-204) as antidepressant related genes/expressed sequence tags. Then, we developed our original cDNA microarrays, on which the 194 clones out of ADRG1-204 were spotted. With this ADRG microarray, we found that the expression of a spot, ADRG55, which representing cysteine string protein (CSP), was significantly increased in rat brain after chronic treatment with a selective serotonin reuptake inhibitor, sertraline. In the present study, reverse transcription-polymerase chain reaction analysis confirmed the induction of CSP at mRNA levels in rat frontal cortex after chronic treatment with two different classes of antidepressants, imipramine or sertraline. Western blot analysis also revealed that CSP-immunoreactivity was increased after antidepressant treatment. In conclusion, our data suggest that CSP is one of the common functional molecules induced after chronic antidepressant treatment.
Assuntos
Antidepressivos/farmacologia , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/fisiologia , Proteínas de Membrana/genética , Sertralina/farmacologia , Animais , Antidepressivos Tricíclicos/farmacologia , DNA Complementar , Depressão/tratamento farmacológico , Depressão/fisiopatologia , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/fisiologia , Proteínas de Choque Térmico HSP40 , Imipramina/farmacologia , Masculino , RNA Mensageiro/análise , Ratos , Ratos Sprague-DawleyRESUMO
PURPOSE: For assessment of the antinociceptive potency of antidepressants, we compared the antinociceptive effects of serotonin selective reuptake inhibitors (SSRIs) and classical tricyclic antidepressants (TCAs) in rats. We also attempted to elucidate the monoamine receptor subtypes predominantly involved in the antinociceptive effect of antidepressants. METHODS: Male Wistar rats received SSRIs (sertraline, fluvoxamine, and citalopram) or TCAs (imipramine and desipramine) intraperitoneally, and the reaction time until pain response in the hot plate test and licking time in the formalin test were measured 60 min later. We also observed the effects of prazosin (an alpha(1) antagonist), WB-4101 (a selective alpha(1A) antagonist), yohimbine (an alpha(2) antagonist), WAY-100635 (a selective 5-HT(1A) antagonist), and ketanserin (a 5-HT(2) antagonist), which were simultaneously administered with imipramine or desipramine, on the antidepressant-induced antinociceptive effect in the formalin test. RESULTS: In the hot plate test, desipramine, 20 mg.kg(-1), but not imipramine or sertraline, produced a significant increase in reaction time. In the formalin test, desipramine and imipramine produced significant reductions in the licking time at over 5 mg.kg(-1) and at over 10 mg.kg(-1), respectively. These reductions were nearly complete at 20 mg.kg(-1). On the other hand, both SSRIs induced significant reductions in the licking time only at 20 mg.kg(-1). Prazosin, WB-4101, and ketanserin significantly antagonized the antinociceptive effect of 10 mg.kg(-1) of imipramine. However, imipramine-induced antinociception was not affected by yohimbine and WAY-100635. Prazosin and ketanserin also significantly suppressed antinociception by 5 mg.kg(-1) of desipramine. CONCLUSION: These findings suggest that classical TCAs are likely to have a therapeutic advantage over SSRIs for pain control. In addition, it is likely that central alpha(1) adrenoceptors and 5-HT(2) receptors are predominantly involved in imipramine- and desipramine-induced antinociception.
Assuntos
Doenças do Sistema Nervoso Autônomo/sangue , Neuropatias Diabéticas/sangue , Dopamina/sangue , Falência Renal Crônica/sangue , Norepinefrina/sangue , Diálise Renal , Ácido 3,4-Di-Hidroxifenilacético/sangue , Doenças do Sistema Nervoso Autônomo/complicações , Neuropatias Diabéticas/complicações , Ácido Homovanílico/sangue , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Metanefrina/sangueRESUMO
PURPOSE: To determine the optimal tube current for spiral CT for lung cancer screening. MATERIAL AND METHODS: Low-dose spiral CT images from 20 subjects were obtained with 50 mA, 25 mA, 10 mA and 5 mA tube currents. The accuracy in detecting 21 nodules measuring 3 to 14 mm in diameter was tested using receiver operating characteristics (ROC) to determine the diagnostic accuracy and statistical significance. RESULTS: Compared with 50 mA, 25 mA showed no statistical difference. A significant difference was seen between 50 mA and 5 mA images and between 25 mA and 10 mA images, in the detection of lung parenchymal nodular lesions. CONCLUSION: Approximately 25 mA is the optimal tube current for the detection of pulmonary nodules as it allows a reduction of the radiation dose without sacrificing diagnostic accuracy.
Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adenocarcinoma/diagnóstico por imagem , Idoso , Feminino , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Curva ROCRESUMO
The pharmacokinetics of panipenem/batamipron (Carbenin; PAPM/BP) was studied in 17 neonates of the postconceptional age (PCA) of 25.6 to 43.1 weeks. PAPM/BP was administered at 10 mg/kg to 20 mg/kg every 12 hours over 60 minutes by intravenous infusion. Blood samples were obtained just prior to the infusion, one or two hours and six hours after the infusion. All the data for the 85 serum PAPM concentrations were analyzed by one-compartment model using a nonlinear mixed-effect model (NONMEM). The pharmacokinetic parameters in these population are given below: CLPAPM; 0.239 +/- 0.206 (L/hr), VdPAPM; 0.97 +/- 0.80 (L), Half Life; 3.1 +/- 0.5 (hr). Half life in the patients with PCA < 34 (2.66 +/- 0.44 hr) were significantly lower (p < 0.001) than that with PCA > or = 34 (3.39 +/- 0.23 hr). Our results suggest that postnatal alterations in the PAPM excretion are related to maturational changes in the renal function and that we should consider the values of PCA when determining the initial PAPM/BP dosing regimen in neonates. We conclude that the dosage of 10 mg/kg to 20 mg/kg every 12 hours are adequate treatment for neonatal infectious disease.
Assuntos
Quimioterapia Combinada/farmacocinética , Infecções Bacterianas/tratamento farmacológico , Infecção Hospitalar/tratamento farmacológico , Esquema de Medicação , Quimioterapia Combinada/administração & dosagem , Feminino , Meia-Vida , Humanos , Lactente , Recém-Nascido , Infusões Intravenosas , Unidades de Terapia Intensiva Neonatal , Masculino , Taxa de Depuração Metabólica , Modelos Biológicos , Tienamicinas/administração & dosagem , Tienamicinas/farmacocinética , beta-Alanina/administração & dosagem , beta-Alanina/análogos & derivados , beta-Alanina/farmacocinéticaRESUMO
The aim of this study was to determine the sensitivity of 201Tl-chloride for small lung cancers. The study subjects consisted of 13 cases of surgically verified lung cancer smaller than 2 cm who had undergone 201Tl-SPECT prior to surgery, owing to the difficulty of establishing a diagnosis of lung cancer based on diagnostic CT. Among 13 cases, four showed positive accumulation in early and delayed SPECT, and nine negative, with a degree of accumulation of 31% (4/13).