Quantification of striatal dopamine transporters with 123I-FP-CIT SPECT is influenced by the selective serotonin reuptake inhibitor paroxetine: a double-blind, placebo-controlled, crossover study in healthy control subjects.

Dopamine transporter (DAT) imaging with (123)I-FP-CIT ((123)I-N-omega-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenyl)nortropane) SPECT is frequently used to detect loss of nigrostriatal cells in parkinsonism. Recent (123)I-beta-CIT ((123)I-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane) studies have shown a significant increase in striatal-to-nonspecific beta-CIT binding ratios after treatment with selective serotonin reuptake inhibitors (SSRIs). Due to similarities between (123)I-beta-CIT and (123)I-FP-CIT (both are derived from cocaine and show relatively high affinity for the DAT and the serotonin transporter [SERT]), we hypothesized that quantification of striatal (123)I-FP-CIT binding may be influenced by SSRIs. Moreover, we hypothesized that (123)I-FP-CIT in humans binds not only to DATs but also to central and peripheral SERTs. METHODS: To study the influence of the SSRI paroxetine on (123)I-FP-CIT binding to DATs in the striatum, we conducted a double-blind, placebo-controlled, crossover study with paroxetine in 8 healthy young male control subjects. In addition, we studied whether paroxetine was able to block (123)I-FP-CIT binding in SERT-rich brain areas and in lung tissue, as lung tissue contains a considerable amount of SERTs. Participants were pretreated for 2 d with paroxetine (20 mg/d) or placebo at 2 sessions (crossover design), and brain SPECT was performed 1 and 3 h after (123)I-FP-CIT injection, whereas lung uptake was measured 2 h after injection. RESULTS: Compared with placebo pretreatment, we found after paroxetine pretreatment a statistically significant increase (approximately 10%) in specific striatal-to-nonspecific (123)I-FP-CIT binding ratios at 3 h after injection, a time point at which striatal (123)I-FP-CIT binding ratios are stable. In addition, after paroxetine treatment, statistically significantly lower binding ratios were found in SERT-rich brain areas (e.g., at 1 h after injection, midbrain-to-cerebellar ratios were approximately 90% lower) as well as significantly lower uptake in lung tissue was found (approximately 40% lower after paroxetine). CONCLUSION: In this study we show that the quantification of striatal (123)I-FP-CIT binding to DAT is significantly increased by the SSRI paroxetine in humans. To our knowledge, this is the first study which shows that (123)I-FP-CIT binds in vivo in humans not only to DATs but also to central SERTs and SERTs in lung tissue.     

Histochemical characteristics of soleus muscle in angiotensin-converting enzyme gene knockout mice.

We examined the histochemical characteristics of soleus muscle in the angiotensin-converting enzyme (ACE) gene (Ace in mice, ACE in humans) knockout mice. Serial sections of soleus muscle of wild-type (Ace+/+, n=20) and heterozygous mutant (Ace+/-, n=24) mice were stained for myosin adenosine triphosphatase activity to identify different muscle fiber types. Capillaries were visualized by amylase-periodic acid-Schiff staining. ACE activity in the serum and gastrocnemius muscle was higher in male mice than in female mice. Female and male Ace+/- mice had markedly lower ACE activity in the serum and the gastrocnemius muscle than did female and male Ace+/+ mice, respectively. In both male and female mice, the composition of fiber types (type I and IIa) did not differ significantly between Ace+/+ and Ace+/- mice. There was no significant gender difference in capillary density. Ace+/- mice had significantly more capillaries around type IIa fibers (5.44 +/- 0.18 vs. 5.01 +/- 0.13, p<0.05) than Ace+/+ mice. The differences in the number of capillaries around type I fibers and in the number of capillaries around per fiber (capillary:fiber ratio) between Ace+/- and Ace+/+ mice were not significant (p<0.1). There was no significant difference in the mean cross-sectional area occupied by one capillary and the number of capillaries per fiber area between Ace+/+ and Ace+/- mice. In conclusion, knockout of the Ace gene in mice increased capillary density, as expressed by the mean number of capillaries around type IIa fibers. This finding suggests a possible mechanism for the cardioprotective effects of ACE inhibitors.     

Chronic voice hoarseness: when is it an emergency?

We report a 68-year-old man with chronic voice hoarseness, who presented to the emergency room with left-sided chest and hypochondrial pain. Chest radiograph showed a large mediastinal mass confirmed to be a thoracic aortic aneurysm by an emergent computed tomography scan. Examination and investigations of a patient with voice hoarseness and chest pain should focus on looking out for dissecting or leaking aneurysms, which may be catastrophic if missed.     

Correlation of Unbound Plasma Clearances of Fifteen Extensively Metabolized Drugs Between Humans and Rats

Unbound plasma clearances (CLu) in humans and rats of 15 extensively metabolized drugs (phe-nytoin, hexobarbital, pentobarbital, phenylbutazone, warfarin, tolbutamide, valproate, phenobarbital, amobarbital, quinidine, chlorpromazine, propranolol, pentazocin, antipyrine, and diazepam), studied earlier by Sawada et al. (J. Pharmacokin. Biopharm. 13:477–491, 1985), were calculated. It was found that the ratio of CLu per square meter of body surface area between human and rat ranged from 0.38 for pentobarbital to 2.34 for tolbutamide, with a mean ratio of 1.07. When body weight (BW) was used for correlation, the mean CLu was proportional to BW ^{0.657±0.0935}. A rationale for the above empirical findings is postulated. The present study seems to indicate the existence of a general similarity or predictability in the CLu of drugs between rats and humans. Low correlations were generally obtained when total (bound and unbound) plasma clearances were used for comparison.     

Granular cell myoblastoma of the extrahepatic biliary system

We have reported our experience with two cases of granular cell myoblastoma, bringing the total number of cases to 29. Granular cell myoblastoma of the extrahepatic biliary system is a rare benign tumor that affects black women predominantly. Both black men in this study had multiple lesions involving the skin and biliary system. Surgery is necessary for tissue diagnosis and curative resection. Tumors involving the common bile duct or common hepatic duct require wide local excision and bilioenteric anastomosis. The cause is uncertain, but present data indicate a neuroectoderm origin.     

11例泌尿生殖相关多原发癌的报告

本文报告我科1985年～1995年间11例与泌尿器官相关的多原发癌。结合文献重点强调多原发癌有别于晚期转移癌,它是人体内同时或异时存在的两种或两种以上各自独立的原发癌,如能及早积极手术治疗辅以其他疗法则其预后不比单原发癌差。并对其发病率、病因及可能的发病机制等进行了讨论。     

Memory function and serotonin transporter promoter gene polymorphism in ecstasy (MDMA) users

Although 3,4-methylenedioxymethamphetamine (MDMA or ecstasy) has been shown to damage brain serotonin (5-HT) neurons in animals and possibly humans, little is known about the long-term consequences of MDMA-induced 5-HT neurotoxic lesions on functions in which 5-HT is involved, such as cognitive function. Because 5-HT transporters play a key element in the regulation of synaptic 5-HT transmission it may be important to control for the potential covariance effect of a polymorphism in the 5-HT transporter promoter gene region (5-HTTLPR) when studying the effects of MDMA as well as cognitive functioning.The aim of the study was to investigate the effects of moderate and heavy MDMA use on cognitive function, as well as the effects of long-term abstention from MDMA, in subjects genotyped for 5-HTTLPR. A second aim of the study was to determine whether these effects differ for females and males. Fifteen moderate MDMA users (<55 lifetime tablets), 22 heavy MDMA+ users (>55 lifetime tablets), 16 ex-MDMA+ users (last tablet > 1 year ago) and 13 controls were compared on a battery of neuropsychological tests. DNA from peripheral nuclear blood cells was genotyped for 5-HTTLPR using standard polymerase chain reaction methods.A significant group effect was observed only on memory function tasks (p = 0.04) but not on reaction times (p = 0.61) or attention/executive functioning (p = 0.59). Heavy and ex-MDMA+ users performed significantly poorer on memory tasks than controls. In contrast, no evidence of memory impairment was observed in moderate MDMA users. No significant effect of 5-HTTLPR or gender was observed.While the use of MDMA in quantities that may be considered "moderate" is not associated with impaired memory functioning, heavy use of MDMA use may lead to long lasting memory impairments. No effect of 5-HTTLPR or gender on memory function or MDMA use was observed.