[Statistical parametric mapping analysis of 18F-FDG PET in Parkinson's disease with mild cognitive impairment].

Objective: To investigate the characteristics of cerebral metabolism associated with mild cognitive impairment (MCI) Parkinson's disease (PD), cognitive normal PD and normal control to find a PET biomarker for the diagnose and estimate of PD-MCI. Methods: Forty-seven patients diagnosed with PD (included 15 with mild cognitive impairment) and 20 control subjects were enrolled. All the subjects were evaluated with FDG-PET and clinical scale. The statistical parametric mapping (SPM) were analyzed to determine metabolic patterns that may be useful in differentiating between the three groups. Results: SPM analysis showed that significant hypometabolism were observed in both side of front lobe, parietal lobe, left temporal lobe and left occipital lobe; in the contrast, the relative hypermetabolism had been observed in the cerebellum, vermis, hippocampus and supplement motor area (SMA) in patients with PD-MCI. PD without MCI showed hypometabolism in both side of front lob, caudate and putamen. PD-MCI showed that the significant hypermetabolism were in the insular and cerebellum while hypometabolism were in the both side of occipital compared to PD without MCI. Conclusion: A voxel-by-voxel based SPM method i. e. SPM8 analysis by PET scan is an effective way to analysis the FDG uptake pattern of PD patients. The hypermetabolism in the insula and cerebellum and hypometabolism in the both side of occipital may be a biomarker for make a diagnosis of PD-MCI.

Intracranial epidermoid cyst with hemorrhage: MR imaging findings.

We present a case of a 28-year-old woman with a cerebellopontine angle and prepontine cistern epidermoid cyst with unusual signal intensity. She presented with cranial nerve neuropathy and unsteady gait. MR imaging showed a tumor mass with central area of hemorrhage and a focal area of heterogeneous signal intensity with spotty enhancement, which correlated histologically to old blood in a cystic lumen and granulation of a cystic wall, with a large area of hemorrhage and mild vascularity.

Follow-up of bilateral subthalamic deep brain stimulation for Parkinson's disease.

PURPOSE: To demonstrate the effects of bilateral subthalamic deep brain stimulation (STN-DBS) in the treatment of Parkinson's disease (PD) after 4-45 months' follow-up. METHOD: Between 04/01 and 12/04, 46 PD patients were operated on with bilateral STN-DBS. All of them were evaluated with Unified Parkinson's Disease Rating Scale (UPDRS) parts II-V before surgery and 4-45 months after surgery. The amelioration of miscellaneous symptoms and decrease of medication dose, respectively, were compared. Main side effects were observed. FINDINGS: After surgery, both the score of activities of daily living (ADL) and the UPDRS motor score decreased significantly (p < 0.001). Among the PD symptoms, tremor was improved best. Rigidity, bradykinesia, axial symptoms, facial expression and dyskinesia were all improved, although to a lesser extent, while speech was not improved. Medication dose was decreased significantly (p < 0.001). According to the time of follow-up, 4 groups were classified (4-12 months, 13-24 months. 25-36 months and 37-45 months group). ADL, UPDRS motor score and dyskinesia subscore improvement were compared among these groups. No significant difference existed. No life threatening complications occurred. Main side effects included hypophonia, dyskinesia, confusion, depression. CONCLUSIONS: Bilateral STN-DBS is a satisfying surgical method for the treatment of advanced PD. It can improve the cardinal PD symptoms up to 45 months. Complications and side effects were rare and usually temporary or reversible.

Modeling of dispersed-drug release from two-dimensional matrix tablets.

A mathematical model was developed and analytical solutions were obtained for dispersed-drug release from two-dimensional matrix tablets in a perfect sink. This model can be used to describe kinetics of solute release from matrices with isotropic or anisotropic properties. Moving boundaries of dispersed-drug in both radial and axial directions and release kinetics were predicted by the model. Various factors influencing release kinetics were analyzed including the ratio of initial solute loading (C0) to solute solubility (Cs), the anisotropy of the matrix and the aspect ratio of tablet radius to the half-thickness. The model is also applicable to 1-D planar or 1-D cylindrical geometries when R/H is larger than 100 or smaller than 0.01.

Zona fasciculata-like cells determine the response of plasma aldosterone to metoclopramide and aldosterone synthase messenger ribonucleic acid level in aldosterone-producing adenoma.

The different responses of plasma aldosterone to ACTH and angiotensin II in aldosterone-producing adenoma (APA) is thought to be due to the various cellular compositions of the tumors. To investigate whether the dopaminergic regulation of aldosterone in APA is also dependent on the cellular types, we studied the effects of metoclopramide on plasma aldosterone in six patients with APA. The messenger RNA (mRNA) levels of aldosterone synthase (P450aldo), 11 beta-hydroxylase (P450(11) beta), and 17 alpha-hydroxylase (P450(17) alpha) of APA and normal adrenal glands were determined by competitive polymerase chain reaction. After administration of metoclopramide (an antagonist of dopamine-2 receptor), the increment of plasma aldosterone correlated inversely with the percentage of zona fasciculata cells of APA. The mRNA level of P450aldo in the tumorous portion was much higher, whereas the levels of P450(11) beta and P450(17) alpha mRNAs were lower, than those of the nontumorous portion and normal adrenals. There was a correlation of the percentage of zona fasciculata cells in APA with the levels of P450aldo and P450(11) beta mRNAs, but not with P450(17) alpha mRNA. These results suggest that differential responsiveness of plasma aldosterone to metoclopramide may be due to various proportions of different cell types in APA that may have different expression of dopamine-2 receptor. In addition, this histologically dependent expression was present at the transcriptional level of the gene responsible for aldosterone biosynthesis.

Mucin expression in mucinous carcinoma and other invasive carcinomas of the breast.

To investigate mucin expression in breast cancer, immunohistochemical staining was performed on 30 mucinous carcinomas and 95 non-mucinous invasive carcinomas. MUC2 expression was detected in all mucinous carcinomas, but only in 11.1% of invasive ductal carcinomas, and in none of the invasive lobular carcinomas and medullary carcinomas. MUC1 is often expressed in invasive breast carcinoma, but not in medullary carcinoma. Strong cytoplasmic staining was seen in invasive ductal carcinoma, in contrast to surface membrane staining in mucinous carcinoma and intracytoplasmic vacuole staining in invasive lobular carcinoma. CA19-9 and CA50 expression in more than 25% of tumor cells was seen in 17.2 and 16.0% of invasive ductal carcinomas, respectively, but not in mucinous carcinomas. CA125 and human gastric mucin were rarely expressed in breast cancer, irrespective of histologic type.

In situ detection of Epstein-Barr virus in breast cancer.

Epstein-Barr virus (EBV) is strongly associated with nasopharyngeal carcinoma and some lymphoepithelioma-like carcinomas from other anatomic sites. This study investigates the presence of EBV in breast cancer. Immunohistochemistry for EBV proteins (EBV nuclear antigen-2 and latent membrane protein-1) and in situ hybridization for EBV-encoded small nuclear RNAs (EBER-1 and -2) were performed in 60 invasive breast cancers. None of the 60 breast cancer samples showed detectable EBV. These results suggest that EBV may not play a significant role in the etiology of breast cancers in Taiwan.

p27 expression as a prognostic factor of breast cancer in Taiwan.

p27Kip1 is a member of the Cip/Kip family of cyclin-dependent kinase inhibitors. It binds to a variety of cyclin/CDK complexes, inhibits kinase activity, and blocks the cell cycle. Absent or reduced p27 expression has been shown to be a significant predictor of poor survival in breast, colorectal, prostate, non-small cell lung and esophagus carcinomas. An immunohistochemical assay was performed on 169 patients with primary breast cancers to evaluate the biologic significance of p27 expression. Decreased p27 expression was significantly associated with high grade (P = 0.00025), negative estrogen receptor (P = 0.00004), and negative progesterone receptor (P = 0.0038) breast cancers. Univariate analysis reveals that p27 expression inversely correlated significantly with overall survival (P = 0.0001). By multivariate analysis, p27 predicted the overall survival independently (P = 0.0096). Our study indicates that p27 expression is an independent prognostic marker of breast cancer in Taiwan.

Proliferating cell nuclear antigen (PCNA) immunolabeling as a prognostic factor in invasive ductal carcinoma of the breast in Taiwan.

To evaluate the prognostic significance of proliferating cell nuclear antigen (PCNA) in breast cancer, an immunohistochemical assay was performed in 150 patients with invasive ductal carcinomas. The PCNA labeling index (PCNA-LI) was classified into two subgroups at a cut-off point of 45% that gave the best prognostic estimates for PCNA in survival analyses. Seventy-eight tumors had a low PCNA-LI of < or =45% and 72 tumors had a high PCNA-LI of >45%. A high PCNA-LI correlated significantly with p53 overexpression (P<0.03), positive axillary node (P<0.04), short disease-free survival (P<0.001) and overall survival (P<0.0002), but not with other factors. In multivariate analysis, the PCNA-LI predicted the disease-free (P<0.008) and overall survival (P = 0.0007) independently. Our study indicates that the PCNA-LI has independent prognostic value.

The prognostic significance of tumor angiogenesis in Taiwanese patients with invasive ductal breast carcinomas.

Angiogenesis plays an important role in tumor growth and metastasis. We performed an immunohistochemical study by anti-CD31 antibody to investigate the prognostic significance of microvessel count (MVC) in 163 Taiwanese patients with primary invasive ductal breast carcinomas. Univariate analysis revealed that MVC per 200x field correlated significantly with disease-free (P < 0.001) and overall survival (P < 0.0008). In 74 patients with node-negative tumors, MVC also significantly correlated with disease-free (P < 0.03) and overall survival (P < 0.007). Multivariate Cox regression analysis demonstrated that MVC is an independent factor in predicting disease-free (P < 0.02) and overall survival (P < 0.02). Our study confirms that tumor angiogenesis as measured by MVC is a reliable independent prognostic factor of breast cancer.

p53 point mutation enhanced by hepatic regeneration in aflatoxin B1-induced rat liver tumors and preneoplastic lesions.

Aflatoxin B1 (AFB1) is a well-known mutagen and carcinogen which induces human hepatocellular carcinoma (HCC). It has been found to be an important factor in inducing a high frequency of codon 249 mutation in the p53 gene. We characterized p53 mutations in specimens from preneoplastic lesions or tumors from the liver of rats induced by AFB1 with or without regeneration by partial hepatectomy treatment. PCR-SSCP and direct sequencing were used for screening and identification of p53 gene mutations in these samples. In rats treated with AFB1 with or without liver regeneration, 29% (5/17) of rats with hepatoma or neoplastic lesion had p53 mutation. No p53 mutations were found in the tumor samples from the rats without liver regeneration. However, in samples from the rats with liver regeneration, 38% (5/13) of the rats with hepatoma or neoplastic lesion were found to have p53 mutations. In one of these samples, we also observed a transversion mutation G --> T on codon 247, compared to codon 249 in humans. These findings suggest that the process of hepatocarcinogenesis induced by AFB1 does not necessarily involve p53 mutation, but mutation of the p53 gene can be enhanced by liver regeneration and that there is a possibility of a high mutability of the third base of codon 247, even though there is a small probability of detecting such a mutation in rats due to its silent mutation.

Correlation of expression of CD44 isoforms and E-cadherin with differentiation in human urothelial cell lines and transitional cell carcinoma.

Using immunostaining, immunoblot, reverse-transcriptase polymerase chain reaction and Southern blot, we found that expressions of CD44 isoforms and E-cadherin were very closely linked and were correlated with the differentiation status in human urothelial cell lines and clinical specimens of transitional cell carcinoma. Normal urothelium, well to moderately differentiated cell lines and surgical samples expressed E-cadherin and large CD44 isoforms containing exon v6, which was pivotal in metastasis of rat pancreatic cell line model. Poorly differentiated cell lines and surgical samples, were E-cadherin-negative and expressed primarily standard form CD44, which did not contain exon v6. We concluded that CD44v6 isoforms and E-cadherin were both down-regulated during the carcinogenesis of urothelium. The large exon v6 containing CD44 isoforms were readily detected in normal urothelium, therefore, were not likely linked to cancer metastasis. E-cadherin and CD44v6 may be used as differentiation markers for human urothelial tumors. Immunohistochemical study solely with antibody against epitopes encoded by exon v6 alone is not informative enough as other alternatively spliced exons may change the function of CD44v6 isoforms.

Differential expression of type 1 angiotensin II receptor mRNA and aldosterone responsiveness to angiotensin in aldosterone-producing adenoma.

Aldosterone secretion in most patients with aldosterone-producing adenomas (APAs) is typically unresponsive to angiotensin II stimulation (AII-unresponsive, AII-U). In some patients, however, plasma aldosterone increases in response to AII stimulation (AII-responsive, AII-R). This differential aldosterone responsiveness could be related to the levels of type 1 AII receptors (AT1R) in the APA. To test this hypothesis, plasma aldosterone levels in response to upright posture and/or sequential high- and low-salt diets were measured by radioimmunoassay in nine patients with APAs. AT1R mRNA levels in the adenomas were quantified by competitive reverse transcription-polymerase chain reaction and correlated to the cellular composition of the adenoma. Two patients were categorised as AII-R by an increase of plasma aldosterone greater than 50% over the baseline. The remaining seven patients who had blunted plasma aldosterone responses were classified as AII-U. Histologically, the AII-R APAs consisted predominantly of zona glomerulosa (ZG)-like cells (> 90%), while the AII-U APAs contained zona fasciculata (ZF)-like cells ranging from 28 to 72%. There was an inverse relationship between the levels of AT1R mRNA in the APA and the percentage of ZF-like cells in the adenoma (n = 9, r = 0.73, P < 0.05). In situ hybridisation findings demonstrated that AT1R mRNA was more uniform and intensive in ZG-like cells than in ZF-like cells. These results suggest that heterogenous aldosterone responsiveness to angiotensin in APAs is histologically dependent and related to the differential expression of AT1R mRNA in the adenoma.

Pregnancy associated with primary hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma is a rare complication of pregnancy. CASES: Three cases of pregnancy complicated by primary hepatocellular carcinoma were seen at our hospital in 3 years. Two were diagnosed antepartum and one postpartum. In one instance, the diagnosis came from finding elevated maternal serum alpha-fetoprotein (MSAFP) with normal amniotic fluid (AF) AFP. Positive hepatitis B surface antigen and liver cirrhosis were found in all three cases, but liver enzymes were only slightly elevated. All three women died, as did one of the fetuses. CONCLUSION: Careful MSAFP screening and interpretation, followed by AFAFP and abdominal sonography, seem to be the best tools for early diagnosis of primary hepatocellular carcinoma in pregnant women.

Angiogenesis of endometrial carcinomas assessed by measurement of intratumoral blood flow, microvessel density, and vascular endothelial growth factor levels.

OBJECTIVE: To evaluate the relationship between blood flow in the tumor assessed by color Doppler ultrasound, microvessel density, and vascular endothelial growth factor levels in endometrial carcinoma. METHODS: Forty-nine patients undergoing surgery for endometrial carcinoma were enrolled. Transvaginal color Doppler ultrasound was performed preoperatively and the lowest resistance index (RI) in the tumor was recorded for analysis. Vascular endothelial growth factor in the tumor was quantified by enzyme immunoassay. The microvessel density of the excised tumor was assessed immunohistochemically. The relationships between the corresponding RI, microvessel density, and vascular endothelial growth factor level of the tumor tissues and clinical and pathologic parameters were analyzed. RESULTS: Significantly lower RIs were noted in tumors of stage II or greater (0.37 compared with 0.50, P <.001), of high histologic grade (grade 3) (0.34 compared with 0.49, P =.004), with deep myometrial invasion (one-half depth or greater) (0.39 compared with 0.49, P =.002), with lymphovascular emboli (0.38 compared with 0.49, P <.001), or with lymph node metastasis (0.30 compared with 0.49, P <.001) compared with stage I tumors and tumors of histologic grade 1 or 2, with superficial myometrial invasion, without lymphovascular emboli, or with no lymph node metastasis. Increased vascular endothelial growth factor levels and microvessel density (x200 field) also were detected in tumors of stage II or greater (975 compared with 129 pg/mg, P =.014; and 88 compared with 61, P =.018, respectively), with lymphovascular emboli (1138 compared with 120 pg/mg, P =.002; and 86 compared with 63, P =.023), or with lymph node metastasis (1011 compared with 95 pg/mg, P <.001; and 98 compared with 61, P =. 019). Resistance index, microvessel density, and vascular endothelial growth factor levels in the tumor showed linear correlations (RI compared with microvessel density: r = -.32, P =. 03; RI compared with vascular endothelial growth factor levels: r = -.40, P =.004; microvessel density compared with vascular endothelial growth factor levels: r =.36, P =.011). CONCLUSION: Blood flow assessed by color Doppler ultrasound has histologic and biologic correlations with angiogenesis and vascular endothelial growth factor levels and might play an important role in predicting tumor progression and metastasis in endometrial carcinoma.

Axonal transport maintains taste responses.

Transection of the gerbil's IXth nerve causes gustatory action potentials to decline in 1-6 h; the rate of decline is a linear function of the length of the nerve stump remaining attached to the tongue. To test the implication that taste discharge mechanisms depend upon axonal transport in the IXth nerve, we injected 40 nl of [3H]leucine into the petrosal ganglion of one IXth nerve of the gerbil, Meriones unguiculatus. Subsequent liquid scintillation counting of the petrosal ganglion, IXth nerve segments, and representative areas of the tongue indicated that labeled materials were transported down the IXth nerve primarily to the vallate and ipsilateral foliate taste papillae of the tongue. A significant impairment of axonal transport and a substantial decline in summated IXth nerve taste responses occurred within 2-3 h after colchicine was applied to the IXth nerve trunk between the tongue and the petrosal ganglion. Similarly, cooling the IXth nerve with a 3-10 degrees C thermocouple junction or metal probe impaired axonal transport and caused a taste response decline. Since impulse mechanisms of the nerve trunk continued to function distal to these sites of treatment, we concluded that the maintenance of taste discharges at the level of the taste bud depends upon unimpeded axonal transport.

Quantitative study of fluoride transport during subsurface dissolution of dental enamel.

Previous studies using bovine dental enamel as a model have shown that surface and subsurface dissolution of enamel may be governed by micro-environmental solution conditions. We have now investigated the demineralization phenomenon more rigorously with the primary objective of developing a method for deducing solution species concentration profiles as a function of time from appropriate experimental data. More specifically, in this report, a model-independent method is described for determination of the pore solution fluoride gradients in bovine enamel during subsurface demineralization. Microradiography was used to determine the mineral density profiles, and an electron microprobe technique to determine total fluoride (F) profiles associated with the enamel. In each case, matched sections of bovine enamel were exposed to partially saturated acetate buffers at pH = 4.5 containing 0.5 ppm F for various periods of time (from six to 24 hours). The treated enamel was found to have an intact surface layer and subsurface demineralization. The extent of the demineralization and the depths of the lesions increased with time in all cases. The data were first used to calculate (a) the total F gradients in the enamel at various times, and (b) the local uptake rate of F as a function of time and position. Then, by manipulation of the equations describing the uptake and transport of F, we calculated the pore diffusion rate of F and the micro-environmental solution F concentration in the aqueous pores as a function of time and of distance from the enamel surface. It was also possible to calculate an intrinsic F diffusion coefficient in the pores, which was about 1.0 X 10(-5) cm2/sec, in good agreement with reported values. 14C-sucrose uptake and release experiments with identically prepared demineralized enamel sections were also conducted to provide an independent check on the assumed dependence of porosity on mineral density. The results of this investigation, especially the outcomes relative to this new method for determination of pore solution F gradients during acid attack of the dental enamel, should be valuable in future studies of the mechanism(s) of the action of F in inhibiting dental enamel demineralization.

Electron probe micro-analysis for subsurface demineralization and remineralization of dental enamel.

A quantitative study of fluoride distribution profile changes in dental enamel was conducted by means of electron probe micro-analysis (EPMA). Fluoride-deposited hydroxyapatite powders were chosen as fluoride standards, and analytical conditions were optimized. The lower limit of detection for fluoride was estimated to be 270 ppm, with an accelerating voltage of 5 kV, a specimen current of 40 nA, and a counting time of 40 seconds. Fluoride profiles in fluoride-treated dental enamel, which exhibited intact surface layers and subsurface demineralization, were determined. The results were also compared with those of an acid-abrasion method, and reasonable consistency was found between these two methods, although the acid-abrasion procedure yielded a slightly lower fluoride content in the initial layers, followed by a higher content of fluoride in the deeper layers. The precision of fluoride profile data obtained from EPMA permits further studies to be conducted on the kinetics of subsurface demineralization and intact surface layer formation ("white spot" formation) which is observed during the acid challenge of dental enamel.

Theoretical analysis of drug release into a finite medium from sphere ensembles with various size and concentration distributions.

Release kinetics for heterogeneous sphere ensembles with a dissolved drug, i.e., initial drug loading below or equal to the drug solubility in the matrix, in a finite external medium was modeled with consideration of heterogeneity among and within spheres. Numerical solutions were obtained using the finite element method for sphere ensemble with normal or log-normal distribution of particle size or initial drug loading among spheres. Exact series solutions were derived for ensembles with various initial loading distributions within spheres, namely linear, quadratic, sigmoidal and uniform distribution, using their mean or average radii. Simplified solutions retaining only one term of the series for non-uniform distributions and three terms for uniform distribution were suggested because of their good approximation to the exact solution. The results of finite element analysis showed that the release rate of an ensemble decreased with increasing standard deviation of particle size. Using weight-average radii in the exact solution gave a prediction of release profile closer to that from the actual size distribution than using mean radii. The three non-uniform loading patterns within spheres all showed reduced initial burst and release rate, leading to more steady release rates than uniform loading, among which the sigmoidal distribution offered the best near-zero order release. Non-uniform initial loading among spheres seemed to have insignificant influence on the release profiles. The volume ratio of liquid to a sphere ensemble played an important role in release kinetics. The derived analytical solutions are applicable to multiple spheres or a single sphere in a finite medium or in a perfect sink.