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The risk stratification of young adults between subjects who will develop a mild form of atherosclerosis and subjects who will undergo a severe disease remains inaccurate. In the eighties of the previous century, David JP Barker has demonstrated the relationship between fetal conditions and occurrence of pathologies in adulthood. In this paper, the multiple evidence that might explain the increased susceptibility to severe forms of atherosclerosis, including stroke and cardiac infarct, in subjects who underwent intrauterine growth restriction (IUGR) will be analyzed. Specifically, we will review those inter-connected data indicating an association between a low weight at birth and an adult phenotype which might favor a severe outcome of atherosclerosis. Young and adult subjects born too small (IUGR) or too early (pre-terms) might represent a subgroup of "at risk subjects", more susceptible toward severe forms of atherosclerosis. Given that low birth weight (LBW) may be considered a surrogate of IUGR, this phenotypic feature could be considered among those indispensable clinical data collected in every patient presenting with atherosclerosis, irrespectively of age. According to the hypothesis that structural arterial changes might represent the link between LBW and susceptibility to atherosclerosis later in life, we suggest that the prevention of atherosclerosis should begin at birth. Regenerative and physiological substances such as thymosin Beta-4 could be challenged for a new "arterial regenerative medicine" in the perinatal period. The goal of this new approach should be the reinforcement of the structure of the arterial wall, allowing LBW newborns to avoid the most severe complications of atherosclerosis later in life: a dream that our research could contribute to bringing to life.

Atherosclerosis is one of the leading causes of disability and mortality worldwide. Inflammation, including monocytes, T and B cells, plays a key role in its pathogenesis. Our purpose was to evaluate plasma cells' presence in a large series of carotid artery plaques and the clinical association.Forty-eight consecutive patients treated with carotid endarterectomy were retrospectively analyzed to assess plasma cells' presence inside the plaque. A semiquantitative grading score was applied, ranging from absence, scattered, clusters of 5-10, and sheets of10 plasma cells. Plasma cell's location, as intraplaque, subendothelial or peri-adventitial, was also defined.In 75% of plaques analyzed, plasma cells were detected: scattered in 63.9%, in clusters in 22.2%, and in sheets in 13.9% of cases. In all cases, plasma cells were observed only inside the plaque. In 13.9% and in 11.1% of cases, plasma cells showed, respectively, a concomitant subendothelial or peri-adventitial distribution. In 5.6% of plaques, there was a simultaneous distribution in subendothelial, peri-adventitial layer, and intraplaque. Association between the presence of symptoms and plasma cells infiltrate was found.Our results suggest that plasma cells could be a key parameter linked to plaque instability. Some types of configurations are significantly associated with the occurrence of cerebrovascular symptoms.

The association between Hashimoto's thyroiditis (HT) and papillary thyroid carcinoma (PTC) remains to be elucidated.A total of 484 HT patients were retrospectively subdivided into two groups: 243 without thyroid nodules, TNs (HTN-) and 241 with TNs (HTN+). Fine-needle aspiration cytology was available in 152 HTN+ patients. This group was compared to a group of 161 patients with nodular goiter (NG) without HT. Finally, 70 HTN+ and 37 NG patients underwent surgery.A very high prevalence of suspicious/malignant cytology (Thy 4-5) at the first diagnosis (38/124; 31%) and during the follow-up (6/28; 22%) was found in HTN+ group. In HTN- group, 22/130 (17%) patients developed TN, but none showed malignant features during the follow-up. HTN+ patients had higher prevalence of Thy 4-5 (44/152 = 28.9%) compared to NG patients (12/161 = 7.4%, p 0.0001). Increased independent odds ratio (OR) for malignancy was conferred by serum TSH 1.0 μUI/ml, [OR 1.93, 95% confidence interval (CI) 1.41-2.64, p 0.0001], male sex (OR 3.44, CI 1.48-8.02, p = 0.004) and HT (OR 3.14; CI 1.08-9.31, p 0.05). Malignant histology (mostly PTC) was confirmed higher in HTN+ (48/70, 68.6%) compared to NG (15/37, 40.5%; p 0.05). Higher prevalence of extrathyroidal infiltration (24/48, 50%) and vascular invasion (25/48, 52%) was found in HTN+ vs NG (2/15, 1.3% p 0.01), (3/16, 1.8% p 0.05), respectively.This study confirms higher prevalence of suspicious/malignant cytology and PTC at histology in nodular HT compared to NG, without evidence of malignancy in non-nodular HT patients during the follow-up.

The purpose of this study was to develop a Physician's Spiritual Well-Being Scale (PSpWBS). The significance of a physician's spiritual well-being was explored through in-depth interviews with and qualitative data collection from focus groups. Based on the results of qualitative analysis and related literature, the PSpWBS consisting of 25 questions was established. Reliability and validity tests were performed on 177 subjects. Four domains of the PSpWBS were devised: physician's characteristics; medical practice challenges; response to changes; and overall well-being. The explainable total variance was 65.65%. Cronbach α was 0.864 when the internal consistency of the whole scale was calculated. Factor analysis showed that the internal consistency Cronbach α value for each factor was between 0.625 and 0.794 and the split-half reliability was 0.865. The scale has satisfactory reliability and validity and could serve as the basis for assessment of the spiritual well-being of a physician.

Viscoelastic (VE) dampers have been shown to be an effective energy dissipation device for structures subjected to seismic excitations. When a VE damper is under shear deformation, the temperature within the damper material will rise due to the conversion of mechanical energy into heat. The effect of temperature rise in the VE damper on a viscoelastically damped structure may be significant because the damper stiffness can decrease due to the temperature rise in the VE damper and its energy dissipation capacity may reduce under strong earthquake ground motions. This paper is intended to quantify the temperature rise effect. A VE element which can accurately describe the frequency and temperature dependent behavior of the test results of a VE damper is first presented. The effect of temperature rise within the VE material is included. Seismic response analyses of a viscoelastically damped structure which was studied extensively by shaking table tests are carried out by two analytical methods: a frequency domain analysis and a time domain analysis. Both analyses consider the effects of frequency and ambient temperature of the VE dampers. The frequency domain approach is computationally more efficient. However, it neglects the effect of temperature rise in the analysis. The time domain method is computationally less efficient. However, it can explicitly calculate the temperature rise during the earthquake and evaluate its influence on the structural responses. Finally, parametric studies on the effect of temperature rise within the VE damper material on the seismic response of a viscoelastically damped structure are analyzed and its implications on practical applications are discussed.

Addition of aluminum chloride to the (η4-cyclohexadiene)Fe(CO)3 complex bearing an acid chloride side chain at C-5 gives a cyclic keto complex, whereas Lewis acid assisted intramolecular cyclization of acyclic (η4-butadiene)Fe(CO)3 complexes containing an aldehyde, an ester, or a nitrile functionality produces (σ,η3-allyl)tricarbonyliron complexes. Treatments of the (η4-butadiene)Fe(CO)3 complexes bearing a chromium carbene moiety in refluxing toluene lead to formation of furan derivatives by intramolecular addition of the diene ligand to the chromium carbene carbon center.

Recently, digital video cameras (DVC) have been more popular. In order to attract more customers, the conventional focusing actuator, stepper, in DVC is gradually replaced with the voice coil motor (VCM) because this can reduce the focusing time in DVC. However, the battery consumption and the efficiency of a VCM for DVC are also important since DVC are portable apparatuses. This paper raises a valid method to design a VCM in DVC. The performances of DVC will reach to lower battery consumption, higher efficiency, and shorter focusing time by turning the diameter of a winding coil, the thickness of the magnet and the windings spaces in a VCM.

The key purpose of this study was how we taught the use of benchmark strategy when comparing fraction for fifth-graders in Taiwan. 26 fifth graders from a public elementary in south Taiwan were selected to join this study. Results of this case study showed that students had a much progress on the use of benchmark strategy when comparing fraction after the experiment. This indicated that an experienced teacher played a key role and knew how to help their children lean the use of benchmark appropriately when comparing fraction.

This paper describes the results of an extensive study on the seismic behavior of a viscoelastically damped structure under mild and strong earthquake ground motions. Shaking-table studies were conducted on a 2/5-scale five-story steel model with added viscoelastic (VE) dampers under various ambient temperatures, damper-placement cases, and earthquake intensities. Three types of VE dampers distinguished by dimensions and viscoelastic materials designed to provide the structure with similar damping ratios at room temperature were used. Analytical studies were carried out to predict the equivalent damping ratios and seismic response of the viscoelastically damped structure. Experimental results show that the VE dampers are effective in attenuating seismic structural response under mild and strong earthquake ground motions. Numerical results show that the structural damping and structural response with added VE dampers can be easily and accurately calculated by the proposed analytical methods. The methods are readily available to practical applications.

Thyroid Paragangliomas are exceptionally rare tumors and only 35 documented cases have been reported in the literature. We report an additional unusual male case of thyroid Paraganglioma associated to a chronic lymphocytic thyroiditis and a papillary microcarcinoma. A 45-year-old man presented with a solitary thyroid nodule. Physical examination revealed a smooth, well-circumscribed, firm, mobile, painless thyroid nodule in the right lobe measuring 3 cm. Ultrasound examination showed a 40 mm hypoechoic, non-homogeneous nodule with peri- and intra-nodular vascular flow. An ultrasound-guided fine needle aspiration biopsy was performed showing the presence of atypical cells (Thy 3). He underwent a total thyroidectomy associated to VI level lymphectomy. Histology showed a thyroid Paraganglioma associated to a chronic lymphocytic thyroiditis and a papillary microcarcinoma measuring 0.3 cm in the greatest dimension. Thyroid Paraganglioma is an elusive tumor. It is difficult to diagnose and should be included in the differential diagnosis of all neuroendocrine tumors of the thyroid, even those arising in men or behaving in a locally aggressive fashion.

To assess the relevance of thyroid autoimmunity and TSH as risk factors for malignancy in thyroid nodules (TN).Retrospective analysis on 2053 patients with single/prevalent TN submitted to fine needle aspiration cytology (FNAC). Anti-thyroid autoantibodies (ATA) [anti-thyroperoxidase (TPOAb), anti-thyroglobulin (TgAb)] and TSH were measured. Cytology was classified as benign (class II), indeterminate (class III), and suspicious or malignant (class IV). Histology was available in 301 patients. Associations of malignancy with independent variables were determined by multivariate logistic regression analysis.Higher prevalence of class IV (14.2% vs 6.8%: p0.001) and class III (23.5% vs 17.1%: p0.001) were found in ATA+ vs ATA- TN. Histology confirmed increased prevalence of cancer in ATA+ (p0.05) TN and in those with diffuse lymphocytic thyroid infiltration (p0.05). Interestingly, the prevalence of malignancies observed in operated class III nodules was strikingly lower in ATA+ (1/20, 5%), than in ATA- patients (34/67, 50.7%; p0.001). Increased independent odds ratio (OR) for malignancy was conferred by any ATA [OR 2.21; 95% confidence interval (CI)=1.49-3.29, p0.0001]; TPOAb (OR 2.15; CI=1.42-3.25, p0.0001) and TgAb (OR 1.67; CI=1.05-2.67, p0.05), by serum TSH1.0 μUI/ml (OR 1.95; CI=1.01-3.76, p0.05), and by young age (10-29 yr: OR 2.09; CI=1.02-4.26, p0.05). A formula was calculated to assess the relative contribution of ATA, TSH, and age to the risk of TN malignancy.Both thyroid autoimmunity and increased TSH represent independent risk factors for TN malignancy.

Solitary extramedullary plasmacytoma (SEP) is a rare malignant neoplasm arising from plasma cells most commonly occurring in the nasal cavity, nasopharynx and larynx. Thyroid involvement is rare and less than 75 cases of SEP of the thyroid gland have been reported to date. A 74-year-old woman with an history of multinodular goiter presented with dysphonia and painful neck swelling, related to a rapidly growing nodule in the right thyroid lobe. Thyroid function tests showed subclinical hypothyroidism; no evidence of Hashimoto's disease was found. Ultrasound confirmed the presence of an isoechoic nodule, 35 mm in diameter, with a CDIII vascular pattern. FNAC showed a monotonous population of atypical cells, interpreted as suspicious for malignant neoplasia (Thyr. 4). The patient underwent total thyroidectomy. Histopathological examination showed a unencapsulated neoplasm composed of atypical tumour cells characterized by abundant cytoplasm and eccentric nuclei. At immunohistochemistry, tumour cells revealed diffuse reactivity for CD138 and CD45RB and predominant staining for kappa chains. Pan-cytokeratins, TTF1, thyreoglobulin, calcitonin, CD20 and CD79a were negative. Clinically, a complete multiple myeloma workup was negative. On this basis, a definitive diagnosis of SEP was made. At 16 months follow-up, the patient showed good clinical conditions without evidence of multiple myeloma. In conclusion, SEP should be considered in the differential diagnosis of a rapidly enlarging thyroid nodule. Clinical correlation and immunocytochemistry are crucial in avoiding pitfalls. Surgery remains the best modality of treatment whenever the lesion is localized and easily removable.

On the basis of extensive analytical and experimental investigations, some practical issues associated with the application of viscoelastic dampers to building structures for seismic performance enhancement are considered. It is first shown that the seismic response of a structure can be significantly improved with added dampers. Even at high temperatures, results show that a viscoelastically damped structure can still achieve a significant reduction of structural response as compared to the case with no dampers added. The development of a design procedure for viscoelastic dampers by taking into account the ambient temperature is addressed next, following a modal strain energy approach. Numerical simulation on equivalent structural damping and structural response confirms that the dynamic behavior of structures with added viscoelastic dampers can be satisfactorily predicted by conventional analytical tools. In addition, the design of structures with added viscoelastic dampers can be easily incorporated into a conventional design process.

A (1--3, 1--4)-beta-glucan 4-glucanohydrolase [(1--3, 1--4)-beta-glucanase, EC 3.2.1.73] was purified to homogeneity from extracts of germinated wheat grain. The enzyme, which was identified as an endohydrolase on the basis of oligosaccharide products released from a (1--3, 1--4)-beta-glucan substrate, has an apparent pI of 8.2 and an apparent molecular mass of 30 kDa. Western blot analyses with specific monoclonal antibodies indicated that the enzyme is related to (1--3, 1--4)-beta-glucanase isoenzyme EI from barley. The complete primary structure of the wheat (1--3, 1--4)-beta-glucanase has been deduced from nucleotide sequence analysis of cDNAs isolated from a library prepared using poly(A)+ RNA from gibberellic acid-treated wheat aleurone layers. One cDNA, designated lambda LW2, is 1426 nucleotide pairs in length and encodes a 306 amino acid enzyme, together with a NH2-terminal signal peptide of 28 amino acid residues. The mature polypeptide encoded by this cDNA has a molecular mass of 32,085 and a predicted pI of 8.1. The other cDNA, designated lambda LW1, carries a 109 nucleotide pair sequence at its 5' end that is characteristic of plant introns and therefore appears to have been synthesized from an incompletely processed mRNA. Comparison of the coding and 3'-untranslated regions of the two cDNAs reveals 31 nucleotide substitutions, but none of these result in amino acid substitutions. Thus, the cDNAs encode enzymes with identical primary structures, but their corresponding mRNAs may have originated from homeologous chromosomes in the hexaploid wheat genome.

The development of (1→3,1→4)-β-glucan 4-glucanohydrolase (EC 3.2.1.73) has been examined in germinating wheat (Triticum aestivum cv. Millewa) grain, and in isolated aleurone layers and scutella. Activity is first detected in extracts of intact grain 2–3 days after the initiation of germination and thereafter increases until 6 days. In isolated aleurone layers, (1→3,1→4)-β-glucanase activity is secreted for up to 4 days. Treatment of aleurone layers with gibberellic acid (GA3) results in a 2-fold enhancement of secreted enzyme for the first 2 days, but activity decreases after 2 days. (1→3,1→4)-β-Glucanase secretion from GA3-treated aleurone layers clearly precedes the secretion of amylase and (1→4)-β-xylanase. Small but significant levels of cellulase are secreted from aleurone layers after GA3 treatment. Isolated scutella also secrete (1→3,1→4)-β-glucanase but GA3 has little apparent effect on secretion patterns from this tissue. Proteins secreted from excised aleurone layers and scutella, together with those in homogenates of intact, germinated grain, have been examined by Western blot analysis, using monoclonal antibodies against barley (1→3,1→4)-β-glucanases as probes. In each case the wheat (1→3,1→4)-β-glucanase is recognised only by the monoclonal antibody that is specific for barley isoenzyme El.

Seismic response characteristics of a 25scale steel frame structure with added viscoelastic dampers are studied experimentally. The major emphasis is placed on the ambient temperature effect. It is...

In practice, light secondary systems attached to the massive primary system are treated independently in the seismic design. Evaluation of the secondary systems and their design forces are performed as equivalent static lateral forces applied to the approximate centers of gravity of the systems being analyzed. These design forces, since they are statics based, do not lend themselves to providing realistic design guidelines of secondary systems. In this paper, possible dynamic design considerations for primary‐secondary (P‐S) systems are studied. A simple yet efficient design procedure is developed. It is shown that, while an increase in damping ratio of the secondary system can always decrease the relative displacement between the primary system and the secondary system, there is an optimum damping ratio for minimizing the maximum acceleration of the secondary system. Compromises thus need to be made when there is a conflict in achieving the best global secondary‐system performance. For illustration purpo...

Statistical energy analysis (SEA) techniques, which are very useful in the dynamic analysis of complex systems, are applied to the study of dynamics of primary‐secondary structural systems. The dynamic response of a system consisting of two spring‐coupled oscillators subject to the filtered white‐noise excitation is examined by means of energy and power flow relations. It is shown that the SEA is conceptually simple and the results obtained from this procedure give useful physical insight into secondary‐system dynamics due to the coupling effect. For example, the mean kinetic energy of the secondary system (indirectly excited oscillator) will always be overestimated if the interaction between the two oscillators is ignored. An evaluation of the coupling effect and response behavior of two coupled multimodal subsystems follows. As numerical examples, two beam‐plate systems, one with point coupling and the other with line coupling, are analyzed. Results of the parametric studies are presented.

For more than twenty years, statistical energy analysis (SEA) has been used for the analysis of steady-state response distributions in complex coupled structures and sound-structure systems. However, the steady-state SEA formalism is not directly applicable to the analysis of transient vibrations. In this paper, energy relations, analogous to steady-state SEA power flow relations, are derived for the time-integrated transient response of each oscillator. These energy flow relations can be combined using statistical concepts, to obtain a set of energy balance equations for N coupled multimodal subsystems. It is shown that the time-integrated response of each subsystem can be described in terms of transient input energies and conventional SEA parameters, i.e., modal densities, loss factors and coupling loss factors. By solving the energy balance equations, the time-integrated response of each subsystem can be obtained. The results of experiments, conducted on a coupled structure consisting of two welded plates, are presented to illustrate the applicability of these relations.

The prediction, by the statistical energy analysis (SEA) method, of transient vibration envelopes for coupled systems is investigated. The relation between the time-varying energy transferred between two coupled subsystems and time-varying energies of the subsystems is studied numerically and experimentally. These studies indicate that time-varying energy transmitted between two subsystems is related to the subsystem energies by an apparent time-varying coupling loss factor. It is shown that the apparent coupling loss factor approaches the asymptotic (or steady-state) coupling loss factor as response energies and transferred energies are integrated over progressively larger times. Both the apparent time-varying coupling loss factor and the asymptotic coupling loss factor, determined experimentally, are used in energy balance equations to predict the time-varying vibration envelopes of a system of two point-coupled plates and the results are compared. Although overall response predictions are similar, considerable differences are noted in individual frequency bands. However, no general method for a priori determination of the apparent time-varying coupling loss factor is suggested.

Hypertensive intracerebral hemorrhage (HICH) was once thought to be a one-time event with very rare recurrence, but recent studies have revealed that the recurrent hemorrhage due to hypertension is not unusual. The purpose of this study was to determine the clinical characteristics of HICH among Taiwanese. From June 1988 to December 1999, 1421 HICH patients were admitted to our hospital. Among them, 68 patients (4.8%) had recurrent HICH. We reviewed their medical records and computed tomographic findings. There were 46 males and 22 females (M/F = 2.1) with a mean age of 59.9 +/- 11.9 years at the onset of the second hemorrhage. The median interval between the first two hemorrhages was 22.5 months (range: 1-107 months). Most of the recurrence was within two years of the first hemorrhage (within 1 year in 27.9%, within 1-2 years in 25%). The location of the second hemorrhage was typical for HICH (putamen in 44.1%, thalamus in 33.8%, cerebellum in 5.9%, pons in 4.4%, and caudate nucleus in 1.5%) except for 7 patients (10.3%) who had lobar hematoma. Forty-nine patients (72%) had both hemorrhages located in the supratentorium and in most of them (40 patients) the recurrent HICH occurred contralaterally to the first one. Putaminal-thalamic pattern was the most common (23.5%), followed by the putaminal-putaminal pattern (20.6%). The mortality rate of the second HICH was 17.6%. Seven patients (10.3%) experienced more than 2 episodes of hemorrhages. This report found that the recurrent HICH was not rare among Taiwanese. A substantial proportion (19.1%) of recurrence was after 5 years. The male predominance and risk factor for recurrent HICH require further study.

Human cytochrome P450 3A4 is a major P450 enzyme in the liver and gastrointestinal tract. It plays important roles in the metabolism of a wide variety of drugs, some endogenous steroids, and harmful environmental contaminants. CYP3A4 exhibits a remarkable interindividual activity variation as high as 20-fold. To investigate whether the interindividual variation in CYP3A4 levels can be partly explained by genetic polymorphism, we analyzed DNA samples from 102 Chinese subjects by polymerase chain reaction (PCR)-single-strand conformation polymorphism analysis for novel point mutation in the CYP3A4 coding sequence and promoter region. Using PCR and directed sequencing method to establish the complete intron sequence of CYP3A4 from leukocytes, the complete genomic sequence from exon 1 through 13 of CYP3A4 was determined and published in the GenBank database (accession no. AF209389). CYP3A4-specific primers were designed accordingly. After PCR-single-strand conformation polymorphism and restriction fragment length polymorphism screening, we found three novel mutations; two are point mutations and one is insertion. The first variant allele (CYP3A4*4), an Ile118Val change, was found in 3 of 102 Chinese subjects. The next allele (CYP3A4*5), which causes a Pro218Arg amino acid change, was found in 2 of 102 subjects. We found an insertion in A(17776), designated as CYP3A4*6, which causes frame shift and an early stop codon in exon 9, in one heterozygous subject. We also investigated the CYP3A4 activity in these mutant subjects by measuring the morning spot urinary 6beta-hydroxycortisol to free cortisol ratio with the enzyme-linked immunosorbent assay method. When compared with healthy Chinese population data, the 6beta-hydroxycortisol to free cortisol ratio data suggested that these alleles (CYP3A4*4, CYP3A4*5, and CYP3A4*6) may decrease the CYP3A4 activity. Incidences of these mutations in Chinese subjects are rare. The prevalence of these point mutations in other ethnic groups and its effect on the metabolic activity of CYP3A4 remain to be further evaluated.

A three-phase trial has been done in 11 volunteers. They were given 600 mg phenytoin (Dilantin capsules) in each phase after an overnight fast. In the first study, phenytoin was given alone. In the second phase 400 mg carbamazepine (CBZ) was given at the same time as the phenytoin, and in the third part, 200 mg CBZ t.d.s. was given for one week prior to the phenytoin. Blood samples were taken for 72 h in each phase. Plasma levels of phenytoin and CBZ were determined by HPLC, and plasma protein binding was determined by equilibrium dialysis. The unbound fraction of phenytoin was 0.082, 0.085, and 0.077 in the control, single-dose CBZ, multi-dose CBZ phases, respectively. Single and multiple doses of CBZ decreased the plasma level of phenytoin. The 72-h AUC of phenytoin was 276, 237, and 176 mg h.l-1 in the 3 phases, respectively, and the 72-h AUC of unbound phenytoin was 22.8, 20.5, 13.0 mg h.l-1. The AUC of phenytoin (unbound and total) after multiple doses of CBZ was significantly lower than in the other two phases. The apparent volume of distribution (Vz/f) was 89.9, 110.3, and 121.3 l in the 3 phases, respectively. Through pharmacokinetic analyses, the decreased AUC and increased Vz/f were attributed to decreased bioavailability of phenytoin when CBZ was co-administered.

A 40-year-old normotensive man suddenly developed diplopia, tinnitus and a burning sensation on the left side of his body while driving a motorcycle. He did not complain of headache, nausea or vomiting. Neurologic examination revealed left trochlear nerve palsy and impaired pinprick, temperature and joint position sensation of the left limbs. There was no ptosis or motor deficit. He had a mild bleeding diathesis due to alcoholic liver cirrhosis. Computerized tomography and magnetic resonance image of the brain disclosed hemorrhages in the right midbrain tectum and the left temporal lobe. After nine months of observation, there was nearly complete recovery of symptoms, except for mild residual diplopia. From a literature review, only nine case of midbrain tectal hemorrhage involving the inferior colliculus have been reported. These patients had a unique clinical presentation. Diplopia due to trochlear nerve palsy, either unilateral or bilateral, was present in all of the cases. Tinnitus and sensory disturbance contralateral to the lesion side were very common. Only three patients had risk factors for hemorrhage, including bleeding diathesis, hypertension and vascular anomalies. In the majority of patients, no underlying causes were detected. The outcome was favorable with conservative treatment.

CYP2D6 mediates both alpha-hydroxylation and O-demethylation of metoprolol. In Chinese subjects, CYP2D6*1 (the wild-type) alleles are relatively uncommon. Subjects with P34S (C188--T188) and S486T (G4268--C4268) mutations (CYP2D6J or CYP2D6*10A) are more frequently seen. Recently, the CYP2D6*2 (CYP2D6L) genotype that results in R296C (C2938--T2938) and S486T mutations was also found important. In this study, metoprolol pharmacokinetics was investigated in subjects of these 3 major genotypes.Allele-specific polymerase chain reaction was used to differentiate CYP2D6*1 and CYP2D6*2 alleles from the common CYP2D6*10A allele in Chinese. Subjects with both CYP2D6*1 and CYP2D6*2 have homozygous C188 in the exon 1, whereas subjects with CYP2D6*10A have T188. Metoprolol pharmacokinetics was compared in 16 C188 subjects (6 homozygous CYP2D6*1 subjects and 10 heterozygous CYP2D6*1/CYP2D6*2 subjects), 12 heterozygous C/T188 subjects, and 12 homozygous T188 subjects.No significant difference in plasma concentration profile or urinary alpha-hydroxymetoprolol excretion could be found among subjects with R296C polymorphism (CYP2D6*1/CYP2D6*2). Therefore data from subjects with CYP2D6*1 and CYP2D6*2 were pooled to compare with data from subjects with CTP2D6*10A. The area under plasma concentration curves (AUC) of S-metoprolol was 1411+/-116 (mean +/- SEM, n = 16), 1899+/-120 (n = 12), and 3588+/-435 (n = 12) nmol x hr/L for homozygous C188, heterozygous C/T188, and homozygous T188 subjects, respectively. The urinary recovery of all 4 alpha-hydroxymetoprolol diastereomers was significantly lower in T188 subjects than in C188 subjects.The P34S polymorphism but not the R296C polymorphism resulted in higher metoprolol plasma concentrations and lower urinary metoprolol metabolite levels in Chinese subjects. This finding suggests that a lower dose of metoprolol may be used in subjects with T188 mutation (CYP2D6*10A allele).

Papillary thyroid carcinoma (PTC) is the most common malignant tumour of the thyroid gland. The immunohistochemical profile of PTC is characterized by immunoreactivity of tumour cells for cytokeratins, thyroglobulin, vimentin, EMA and S100 protein. Recently, the presence of a serum protease inhibitor, alpha-1-antitrypsin (A1AT), has been demonstrated in tumour cells of PTC. The aim of our study was to test immunoreactivity of PTC for another inhibitor of proteases, alpha-1-antichymotrypsin (A1ACT).Serial paraffin sections of nine consecutive cases of PTC were tested with anti-A1AT and anti-A1ACT antibodies. No immunoreactivity for A1AT and A1ACT was found in the normal thyroid tissue surrounding each tumour. In seven out of nine cases, tumour cells of PTC showed cytoplasmic immunoreactivity for A1ACT. In two cases, A1ACT was detected even in the nuclei. Immunoreactivity for A1AT was found only in three cases. Two cases of PTC showed no staining for both A1ACT and A1AT. No significant correlation of A1ACT staining was found with various prognostic indices (age of patients, histological pattern, tumour size, presence of regional lymph node metastases). The two cases showing a lack of staining for both A1ACT and A1AT showed a more aggressive clinical behaviour.Our preliminary study shows that A1ACT is expressed by tumour cells in a large proportion of papillary carcinomas of the thyroid gland. Its significance remains, to the best of our knowledge, still unknown. The observation of a more aggressive behaviour in the two cases characterized by the absence of immunoreactivity for both A1ACT and A1AT suggests that the presence or absence of protease inhibitors could play a role in controlling tumour progression in PTC.

Monoamine oxidase B (MAO-B) may play a role in the progression and cause of Parkinson's disease (PD), given consideration of the biochemistry and pathophysiology of the disease, and experiments on primates and humans. Assuming that the structural gene determines enzyme activity, an association study was undertaken to examine MAO-B genetic polymorphisms and look for the unique MAO-B gene alleles which occurred at a higher frequency in PD patients.Sixty-five PD patients, diagnosed according to the criteria set by a Core Assessment Program for Intracerebral Transplantations Committee, and 108 healthy controls were enrolled in this study. Genomic DNA was extracted from peripheral leukocytes by using a puregene kit. Polymerase chain reaction (PCR) was used to amplify the MAO-B genome. The PCR products were screened by restriction enzyme Hae III digestion and analyzed by single-stranded conformational polymorphism (SSCP).Two bands with different mobility shifts, defined as MAO-B allele 1 and allele 2, were observed in SSCP analysis. Neither genotypes nor allelic frequencies of MAO-B showed a significant difference between PD patients and controls in our study.Polymorphism of MAO-B genome was demonstrated in this study. It failed to show an association of a genetic marker with PD. However, this did not necessarily exclude the MAO-B locus from playing a role in causing PD because a polymorphism different from the one evaluated here may show some disease association.

We analyzed the AluI restriction fragment length polymorphism (RFLP) of the apolipoprotein B (apoB) gene to determine the association between AluI allelic distribution and the occurrence of ischemic stroke in Taiwan. A total of 44 healthy volunteers and 159 ischemic stroke patients were included in the study. The allele frequency of AluI was very similar in the two groups, 0.87 in the patient group and 0.89 in the control group, for the major allele A-. The distribution of A-/A-, A-/A+, and A+/A+ genotypes of the patients was not significantly different from that of the controls. Among ischemic stroke patients, the A+ allele of the AluI restriction site was significantly associated with elevated apoB levels. The results of this study suggest that the presence of the rare AluI RFLP may contribute to an elevated plasma apoB level, which is a known risk factor for ischemic stroke.

Biochemical changes inside the brain during acute ictus have been extensively studied by means of magnetic resonance spectroscopy (MRS). Previous reports revealed that cerebral cortical infarction causes reduction of N-acetylaspartate (NAA) and elevation of lactate. This study was designed to evaluate the biochemical changes in subcortical infarction.Nine normal controls and four patients, including two thalamic infarct, one basal ganglia infarct, and one putamen infarct cases were examined using MRS in addition to magnetic resonance imaging (MRI). Evaluation experiments were performed on a Siemens Wagnetom 63SP machine. A spin echo sequence with TE 270 msec was applied for the measurement. The voxel was located at basal ganglia in the controls and at the lesion site, as well as at the contralateral corresponding region in the patients.Three resonance signals were present in the spectrum-NAA, choline-containing compounds (Cho) and creatine-phosphocreatine (Cr). The NAA/Cho and NAA/Cr ratios were reduced significantly on the lesion side compared with the controls. NAA/Cho also decreased on the lesion side compared with the healthy side.There is a remarkable reduction of NAA concentration even in subcortical infarction. Further study is needed for the detection of changes in lactate in patients with subcortical lesion.

Microsatellite polymorphisms of 75 unrelated Taiwanese males were analyzed for (GATA) repeats in DYS19 on chromosome Y and tetranucleotide simple repeats in D12S67 on chromosome 12. A simple nonisotopic technique based on polymerase chain reaction electrophoresis on native polyacrylamide gels followed by silver staining was used. In the 75 unrelated males, four alleles on DYS19 and five alleles on D12S67 were detected. Different allele frequencies, heterozygosity rates and information on the nature of the repeat loci were determined in these unrelated individuals. The resulting polymorphisms are of great assistance in ethnologic studies, forensic investigation and deficiency cases in paternity testing.

The frequency of and reasons for errors in diagnosing various types of cerebrovascular disease at the emergency room of National Cheng Kung University Hospital were analyzed in 548 consecutive patients from January to December 1990. Each patient was evaluated by neurological residents and a bedside diagnosis was made on the basis of history-taking, physical examination, and diagnostic reasoning. The emergency diagnosis was made after finishing the radiological and/or laboratory investigations. The tentative emergency diagnosis of each patient was judged as correct or not by comparison with the final diagnosis, which was based on either the results of specific investigation or on the typical cerebrovascular syndrome ascertained by the attending physicians if the specific investigation was not helpful. If the tentative emergency diagnosis had been judged to be wrong, the cause for the misdiagnosis was determined by reviewing the records of the entire diagnostic process. The diagnosis in the emergency setting was erroneous in 131 (24%) patients. Primary intraventricular hemorrhage, cerebral venous thrombosis and subarachnoid hemorrhage were frequently misdiagnosed as compared with other types of stroke. The explored reasons for diagnostic inaccuracy were: inadequate basic data (46%), reasoning errors (38%), and lack of fundamental knowledge (16%). These results implied that the education and training for diagnosis of subarachnoid hemorrhage in emergency should be enhanced. Deeply comatose states caused diagnostic difficulties in data collection. Diagnostic errors were frequently encountered in unusual stroke or stroke with atypical presentations. To increase diagnostic ability in cerebrovascular emergencies, residents should strive to improve interview and examination skills and reasoning discipline. Modern technology is not a panacea for diagnostic difficulties.(ABSTRACT TRUNCATED AT 250 WORDS)

By means of immunohistochemistry the presence of the growth-associated protein GAP-43 and its codistribution with substance P (SP) and calcitonin gene-related peptide (CGRP) are studied in the human spinal trigeminal, gracile, and cuneate nuclei at perinatal and adult life stages. The results obtained show that the distribution pattern of GAP-43 in the areas examined varies with age and that the immunohistochemical detectability of the protein persists in discrete subregions of the trigeminal and cuneate nuclei of the adult, where its localization closely matches that of SP and CGRP. It is suggested that neuronal plasticity may be pronounced throughout life in areas of the human nervous system involved in the neurotransmission of protopathic stimuli at the first synaptic level. Discrete subregions of the cuneate nucleus, bearing neurochemical characteristics strikingly similar to those of the substantia gelatinosa of the trigeminal subnucleus caudalis are pointed out.

To evaluate the putaminal influence on spinal motoneuron excitability, H-reflex recovery curve (HRRC) was studied in 24 patients with putaminal hemorrhage. Thirteen patients had increased facilitation, most significantly between 150 msec and 300 msec after the conditioning stimulus. It is proposed that putaminal dysfunction may cause an impairment in inhibition of soleus motoneuron excitability. Such a putaminal disinhibition is probably related to a disturbance of the thalamo-striatal and thalamic fasciculus circuits.

Phenytoin is known to be metabolized to form p-hydroxyphenyl-phenyl-hydantoin, possibly via the arene oxide intermediate. The reactive arene oxide may bind to macromolecules irreversibly and cause toxicity. In this study, valproic acid was found to increase the irreversible binding of phenytoin to rat liver microsomes at high concentrations. The effect was similar to that of TCPO and could be reversed by adding glutathione. Valproic acid may increase the hepatotoxicity of phenytoin.

To investigate the autoinduction of carbamazepine (CBZ) metabolism in Chinese, eleven healthy male volunteers joined in this study. There were two phases of drug administration with a wash-out interval of one month, 400 mg CBZ was taken orally in single-dose phase, and 200 mg three times per day were given for seven days in multiple-dose phase. Plasma samples were obtained in series of time after the last dose of drug in each phase. CBZ concentrations were determined by a high pressure liquid chromatography method. A non-linear regression program was applied in a personal computer to estimate the pharmacokinetic parameters. The average CBZ half-lives in single- and multiple-dose phases were 50.1 +/- 12.1 (mean +/- SD) hours and 26.1 +/- 4.2 hours and the clearances were 16.4 +/- 3.3 ml/kg/h and 45.3 +/- 23.4 ml/kg/h respectively, both with significant differences (p less than 0.005). There is evidence to support the presumption of autoinduction in Chinese.

We studied the effects of long-term fish oil (FO) dietary supplementation on brain edema, polymorphonuclear neutrophil (PMN) infiltration, and infarct size in a rat stroke model. Rats were given regular rat chow with or without FO supplement (20% of total calories) for 7 weeks. Body weight did not differ between the two groups. In the FO group, an increase in eicosapentaenoic acid and a decrease in arachidonic acid content in hepatic phospholipids were significant in the phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine but not in the phosphoinositol fraction. Platelet activity reflected by serum thromboxane B2 levels was reduced in the FO group. Postischemic brain edema and PMN infiltration were not different between the two groups. The infarct volume was significantly greater in the FO group (controls: 96 ±7 mm3, n = 49; FO group: 124 ± 6 mm3, n = 53; p = 0.0036). The greater ischemic brain injury in the FO-supplemented animals is probably related to the intraischemic hyperglycemia, which was worse in the FO group than in the control group (controls: 265 ± 19 mg/dl, n = 14; FO group: 340 ± 18 mg/dl, n = 16; p = 0.0079).