In vivo PET imaging of the neuroinflammatory response in rat spinal cord injury using the TSPO tracer [(18)F]GE-180 and effect of docosahexaenoic acid.

PURPOSE: Traumatic spinal cord injury (SCI) is a devastating condition which affects millions of people worldwide causing major disability and substantial socioeconomic burden. There are currently no effective treatments. Modulating the neuroinflammatory (NI) response after SCI has evolved as a major therapeutic strategy. PET can be used to detect the upregulation of the 18-kDa translocator protein (TSPO), a hallmark of activated microglia in the CNS. We investigated whether PET imaging using the novel TSPO tracer [(18)F]GE-180 can be used as a clinically relevant biomarker for NI in a contusion SCI rat model, and we present data on the modulation of NI by the lipid docosahexaenoic acid (DHA). METHODS: A total of 22 adult male Wistar rats were subjected to controlled spinal cord contusion at the T10 spinal cord level. Six non-injured and ten T10 laminectomy only (LAM) animals were used as controls. A subset of six SCI animals were treated with a single intravenous dose of 250 nmol/kg DHA (SCI-DHA group) 30 min after injury; a saline-injected group of six animals was used as an injection control. PET and CT imaging was carried out 7 days after injury using the [(18)F]GE-180 radiotracer. After imaging, the animals were killed and the spinal cord dissected out for biodistribution and autoradiography studies. In vivo data were correlated with ex vivo immunohistochemistry for TSPO. RESULTS: In vivo dynamic PET imaging revealed an increase in tracer uptake in the spinal cord of the SCI animals compared with the non-injured and LAM animals from 35 min after injection (P < 0.0001; SCI vs. LAM vs. non-injured). Biodistribution and autoradiography studies confirmed the high affinity and specific [(18)F]GE-180 binding in the injured spinal cord compared with the binding in the control groups. Furthermore, they also showed decreased tracer uptake in the T10 SCI area in relation to the non-injured remainder of the spinal cord in the SCI-DHA group compared with the SCI-saline group (P < 0.05), supporting a NI modulatory effect of DHA. Immunohistochemistry showed a high level of TSPO expression (38 %) at the T10 injury site in SCI animals compared with that in the non-injured animals (6 %). CONCLUSION: [(18)F]GE-180 PET imaging can reveal areas of increased TSPO expression that can be visualized and quantified in vivo after SCI, offering a minimally invasive approach to the monitoring of NI in SCI models and providing a translatable clinical readout for the testing of new therapies.

Pre-ICH warfarin use, not antiplatelets, increased case fatality in spontaneous ICH patients.

BACKGROUND AND PURPOSE: Anticoagulant and antiplatelets for prevention of ischaemic stroke and cardiovascular diseases may increase the risk of intracerebral hemorrhage (ICH). This study aimed to investigate the influence of pre-ICH use of anticoagulant and antiplatelets on ICH patients. METHODS: Consecutive patients with acute spontaneous ICH registered in a single-center stroke registry during 2001 to 2010 were analyzed and categorized according to their pre-ICH use of warfarin (Group I), antiplatelets (Group II), or neither (Group III). Survival analysis and the Cox proportional hazard model were used to compare between the three groups and the predictors. RESULTS: Of 2021 ICH patients (male, 63.3%; mean age, 62.6 ± 14.4 years) included, there were 94 (4.7%) in Group I, 232 (11.4%) in Group II, and 1695 (83.9%) in Group III. Warfarin users had larger hematoma volume, more intraventricular extension, higher frequencies of lobar ICH, and higher case fatality than non-warfarin users (Groups II and III). The Cox proportional hazard model showed increased 6-month case fatality in pre-ICH warfarin users (adjusted hazard ratio 2.75, 95% confidence interval 2.04-3.72, P < 0.001), but not in pre-ICH antiplatelet users (adjusted hazard ratio 0.95, 95% confidence interval 0.72-1.26). CONCLUSIONS: Intracerebral hemorrhage patients with prior warfarin use, but not antiplatelet use, had significantly higher case fatality at 6 months.

Ultrasound detection and closure of contralateral patent processus vaginalis in pediatric patients with unilateral inguinal hernia and hydrocele: a longitudinal study to prove efficacy in avoiding contralateral hernia development.

BACKGROUND: Open herniotomy has been the gold standard of pediatric hernia treatment with the advantages of simplicity in surgical technique, fast post operative recovery, and minimal recurrence rate, but its inability to prevent hernia development from a contralateral patent processus vaginalis (PPV) after a unilateral herniotomy is its major drawback. By contrast, laparoscopic hernia repair has the advantage of contralateral internal ring inspection, and, therefore, has become popular in recent years, although open herniotomy is still the favorable surgical technique among many surgeons. A simple and reliable tool to detect contralateral PPV will be valuable to surgeons who practice conventional open hernia surgery on children, although ultrasound has been applied for this purpose, but there is no long-term data to support such application. METHOD: The author performed a preoperative ultrasound on the contralateral groins of children undergoing unilateral herniotomy or PPV ligation. If the ultrasound showed no evidence of contralateral PPV, no contralateral surgery was performed. Those patients were then followed up after a long period of time to see whether contralateral hernia or hydrocele was developed or not. RESULTS: 322 pediatric patients were studied from 2006 to 2012. In 96 of the cases (30%), contralateral PPV were identified with ultrasound, and 95% of which were affirmed intraoperatively. In the remaining 226 patients who were without evidence of contralateral PPV, only unilateral surgeries were offered. One of these patients later developed contralateral hernia and required another surgery. The remaining patients were phoned up after a median period of 9 years. 114 of them could be contacted and none of them had developed contralateral hernia or hydrocele. CONCLUSIONS: Ultrasound groin is a valuable tool as an adjunct in pediatric hernia management by detecting contralateral PPV with high accuracy. Surgeon can offer unilateral or bilateral hernia surgery according to the ultrasound finding, and the incidence of contralateral hernia development is negligible. Preoperative ultrasound groin with selective contralateral PPV closure in children can be an alternative to routine laparoscopic hernia repair in avoiding contralateral hernia or hydrocele development. LEVEL OF EVIDENCE: Level 3. TYPE OF STUDY: Retrospective study.

Acute disseminated encephalomyelitis: a follow-up study in Taiwan.

BACKGROUND: Acute-disseminated encephalomyelitis (ADEM) is a demyelinating disorder of the central nervous system, whose epidemiology, clinical presentations and functional outcome are incompletely understood in Asian populations. OBJECTIVE: To assess the clinical presentations, predisposing factors and functional outcome of ADEM in Taiwan. METHODS: 50 patients initially diagnosed with ADEM (male, 19; female, 31) were enrolled from 1991 to 2005. Diagnosis of ADEM or multiple sclerosis was established during a follow-up period of 2-120 months. 8 adult patients were noted to have taken the immunomodulatory drug, levamisole, within 3 months before onset of symptoms. The remaining 42 patients (male, 17; female, 25) were categorised by age as children (<16 years, n = 12), young adults (16-49 years, n = 21) and elderly adults (> or =50 years, n = 9). The clinical manifestations, predisposing factors and radiological findings were compared between different age groups and adult patients with or without levamisole use. Functional outcome was compared by a log-rank test. RESULTS: Preceding upper respiratory tract infection was evident in 21 (50%) patients and only one young-adult patient had received Rubella vaccine immunisation. The frequency of fever was higher in children (p = 0.04) and psychiatric symptoms were more prevalent in elderly patients (p = 0.03). Functional recovery was faster in children than in adults (p = 0.002). Initial Expanded Disability Status Scale score (odds ratio (OR) 1.9, p = 0.03) and no fever (OR 0.04, p = 0.06) were associated with poor outcome (modified Rankin scale > or =2). After a mean (SD) follow-up of 31.8 (9.9) months, 4 (9.5%) patients developed multiple sclerosis (3 (25%) children, 1 (4.7%) young adult, p = 0.03). The neurological disability, radiological and cerebrospinal fluid findings did not differ between patients with and without levamisole use. One elderly adult patient previously receiving levamisole developed multiple sclerosis of relapse-remitting type after a mean follow-up period of 36.9 months. CONCLUSION: The clinical presentations, functional outcome and risk of developing multiple sclerosis differed between different age groups. Functional recovery was faster in children than in adults. Poor functional outcome was related to initial high Expanded Disability Status Scale score and absence of fever.

Effect of plasma glucose on infarct size in focal cerebral ischemia-reperfusion.

Although hyperglycemia has been shown to consistently exacerbate ischemia brain injury following global or diffuse cerebral ischemia, the effect of hyperglycemia in unilateral focal cerebral ischemia remains controversial. Recent advances in thrombolytic therapy have enhanced the clinical significance of postischemic reperfusion. We studied the effect of plasma glucose on ischemic brain injury in a newly developed focal cerebral ischemia-reperfusion model. Rats allowed free access to food until ischemic insult developed intra- and postischemic hyperglycemia and cortical infarction. Rats fasted for 24 hours had blunted hyperglycemic responses. Infarct volumes were correspondingly smaller. The protective effect of fasting was partially abolished by glucose loading during ischemia to induce intra-ischemic hyperglycemia. Glucose loading immediately or 3 hours after focal cerebral ischemia did not significantly alter the protective effect of fasting. Insulin treatment in fed rats before ischemia also reduced hyperglycemic responses and infarct volume. Timing of insulin treatment was also critical in the reduction of ischemic injury. These findings indicate that plasma glucose during the period of ischemia is an important determinant of brain injury in focal cerebral ischemia-reperfusion and there is a therapeutic window for normalization of plasma glucose to be efficacious.

Correlations between peripheral differential leukocyte counts and carotid atherosclerosis in non-smokers.

Substantial evidence clearly indicates the immuno-inflammatory nature of atherosclerosis and the important roles of monocytes and other leukocytes in atherogenesis. The relationship between atherosclerosis and the peripheral monocyte count, however, has been equivocal and uncertain so far. One possible reason may be an opposing effect of different major risk factors of atherosclerosis on the monocyte count, e.g. smoking increases the monocyte count while hypercholesterolemia is accompanied by a lower monocyte count. Since smoking is well shown to increase leukocyte counts prominently in weeks, our study included only non-smokers who participated in a health check program at our hospital from 1996 to 1998 and had received a carotid duplex study with extra payment. Our results revealed the followings: In male non-smokers (n=571), the presence of carotid atherosclerosis was associated with significant increases in the counts of all leukocyte, neutrophil, and monocyte (P<0.005,<0.001 and <0.05, respectively), and, after adjustments for age and body mass index, there were significant positive links between these three leukocyte counts and the severity of carotid atherosclerosis, judged by either the sum score of all carotid plaques or the score of the most severe carotid plaque. On the contrary, in female non-smokers (n=614), there was no significant link between differential leukocyte counts and either the presence or severity of carotid atherosclerosis. These results are compatible with recently recognized sex differences in the mechanism and pathophysiology of atherosclerosis, and together with relevant results in the literature, suggest that monocytes and neutrophils are the main types of leukocytes involved in atherosclerosis.

Anticonvulsant effects of 7-nitroindazole in rodents with reflex epilepsy may result from L-arginine accumulation or a reduction in nitric oxide or L-citrulline formation.

1. To investigate the role of nitric oxide in epilepsy we have studied the effects of agents which affect nitric oxide synthesis in sound-induced seizures in DBA/2 mice and in genetically epilepsy-prone (GEP) rats. 2. The neuronal selective nitric oxide synthase inhibitor, 7-nitroindazole (7-NI) is anticonvulsant in these models with ED50 values against clonic seizures in mg kg-1 i.p. (times following injection) of: 74 (+0.25 h), 120 (+1 h) in DAB/2 mice, and 56 (+0.25 h), 42 (+0.5 h), 36 (+1 h), 28 (+2 h), 38 (+4 h), 93 (+8 h) in GEP rats. 3. Therapeutic indices (locomotor deficit ED50/anticonvulsant ED50) for 7-NI are low, ranging from 0.6 to 1.1 at +0.25 h to +1 h after administration in GEP rats, but are more favourable at later times (1.6 at +2 h and 2.9 at +4 h). 4. The substrate for nitric oxide synthase, L-arginine (500-5000 mg kg-1, i.p. or 100-300 micrograms, i.c.v.) but not D-arginine (300 micrograms i.c.v.) is anticonvulsant in DBA/2 mice. L-Arginine (500-5000 mg kg-1, i.p. or 1800-6000 micrograms, i.c.v.) is a more potent anticonvulsant than D-arginine (1500-2500 mg kg-1, i.p. or 6000 micrograms, i.c.v.) in GEP rats. 5. In DBA/2 mice, L-arginine (30 micrograms i.c.v.) reverses the anticonvulsant effect of 7-NI (50 mg kg-1, i.p.). 6. In GEP rats, low dose L-arginine (25-50 mg kg-1, i.p.) but not D-arginine (50 mg kg-1, i.p.) reverses the anticonvulsant effect of low dose 7-NI (25 mg kg-1, i.p.). A higher dose of L-arginine (500 mg kg-1, i.p.) or 7-NI (50 mg kg-1, i.p.) produces summation of anticonvulsant effect. 7. The product for nitric oxide synthase, L-citrulline (250-831 micrograms i.c.v.), is convulsant in DBA/2 mice. 8. The anticonvulsant effect of the neuronal selective nitric oxide synthase inhibitor, 7-nitroindazole, may therefore be mediated by L-arginine accumulation, as well as by a reduction in nitric oxide and L-citrulline formation in rodent models of reflex epilepsy.

Aetiologies and prognosis of Chinese patients with deep vein thrombosis of the lower extremities.

Deep vein thrombosis (DVT) of the lower extremities is not frequently encountered in Oriental patients. We investigated its aetiology and prognosis in 143 patients (65 males, 78 females), presenting to the National Taiwan University Hospital over 4.3 years, diagnosed by colour Doppler ultrasonography. Swelling and pain of the lower extremities were the most frequent presenting symptoms. The left femoropopliteal veins were more frequently involved than other parts of the lower extremities. In these patients, malignancy with or without intravenous catheterization was the most frequent cause (39 patients, 27%). Other common aetiologies included coagulopathy (29 patients, 20%), immobilization (24 patients, 17%) and catheter-related (13 patients, 9%). No definite aetiology could be determined in 37 patients (26%). During follow-up, 27 patients (19%) died, mostly with malignancy. Pulmonary embolism was noted in 16 patients and was not significantly directly related to death. Compared to similar studies in Caucasian patients, there were significant differences in the aetiology of DVT, with malignancy and coagulopathy more common in these Chinese patients.

Anticonvulsant activity of a mGlu(4alpha) receptor selective agonist, (1S,3R,4S)-1-aminocyclopentane-1,2,4-tricarboxylic acid.

The metabotropic Group III agonist, (1S,3R,4S)-1-aminocyclopentane-1,2,4-tricarboxylic acid (ACPT-1), selective for the mGlu(4alpha) receptor, suppresses sound-induced seizures in DBA/2 mice following its intracerebroventricular (i.c.v.) administration (ED(50) 5.6 [2.9-10.7], nmol i.c.v., 15 min, clonic phase) and in genetically epilepsy-prone (GEP) rats following focal administration into the inferior colliculus (ED(50) 0.08 [0.01-0.50], nmol, 60 min, clonic phase). ACPT-1 also protects against clonic seizures induced in DBA/2 mice by the Group I agonist, (RS)-3,5-dihydroxyphenylglycine (3,5-DHPG) (ED(50) 0.60 [0.29-1.2], nmol i.c.v.) and by the Group III antagonist, (RS)-alpha-methylserine-O-phosphate (MSOP) (ED(50) 49.3 [37.9-64.1], nmol i.c.v.). Another Group III agonist, (RS)-4-phosphonophenyl-glycine (PPG), preferentially activating the mGlu(8) receptor, previously shown to protect against sound-induced seizures in DBA/2 mice and GEP rats, also protects against seizures induced in DBA/2 by 3,5-DHPG (ED(50) 3.7 [2.4-5.7], nmol i.c.v.) and by the Group III antagonist, MSOP (ED(50) 40.2 [21.0-77.0], nmol i.c.v.). At very high doses (500 nmol i.c.v. and above), Group III antagonists have pro-convulsant and convulsant activity. The anticonvulsant protection against sound-induced seizures in DBA/2 mice provided by a fully protective dose (20 nmol, i.c.v.) of the mGlu(4) receptor agonist ACPT-1, is partially reversed by the co-administration of the Group III antagonists, MSOP, (RS)-alpha-methyl-4-phosphonophenylglycine (MPPG) or (S)-2-amino-2-methyl-4-phosphonobutanoic acid (MAP4), in the 20-50 nmol dose range. At doses of 50-200 nmol, MPPG and MAP4 cause further reversal of the ACPT-1 anticonvulsant protection, while the MSOP effect on ACPT-1 protection is abolished at higher doses. In contrast, the anticonvulsant protection against sound-induced seizures in DBA/2 mice provided by a fully protective dose (20 nmol, i.c.v.) of the mGlu(8) receptor agonist PPG, is not significantly affected by the co-administration of the same Group III antagonists, MSOP, MPPG or MAP4. We conclude that activation of either mGlu(4alpha) or mGlu(8) receptors confer anticonvulsant protection in DBA/2 mice. Furthermore, the metabotropic Group III receptor antagonists, MSOP, MPPG, and MAP4 appear to be functionally selective for the mGlu(4) receptor in this system.

Prolonged anticonvulsant action of glutamate metabotropic receptor agonists in inferior colliculus of genetically epilepsy-prone rats.

The anticonvulsant activity of (S)-4-carboxy-3-hydroxyphenylglycine ((S)-4C3HPG) (an antagonist of Group I and an agonist of Group II metabotropic glutamate (mGlu) receptors), of (1S,3S)-1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3S)-ACPD) (an agonist of Group II mGlu receptors), and of L-serine-O-phosphate (an agonist of Group III mGlu receptors) was studied against sound-induced seizures in genetically epilepsy-prone (GEP) rats following bilateral microinjection into the inferior colliculus. All 3 drugs produce dose-dependent suppression of all phases of sound-induced seizures (wild running, clonic and tonic). (S)-4C3HPG produces an immediate and short-lasting (< 2 h) protection against sound-induced seizures with an ED50 value of 4.3 (3.2-5.7) nmol, at 5 min. The preferential agonists of Group II and Group III mGlu receptors produce an immediate, transient (< 10 min) proconvulsant effect followed by a prolonged (> 1 day) anticonvulsant effect against sound-induced seizures. The anticonvulsant ED50 value for (1S,3S)-ACPD is 9 (5-18) nmol at 2 h, and for L-serine-O-phosphate is 36 (6.5-199) nmol at 2 days. It is concluded that mGlu receptor activation potently modifies seizure threshold.

Anticonvulsant actions of LY 367385 ((+)-2-methyl-4-carboxyphenylglycine) and AIDA ((RS)-1-aminoindan-1,5-dicarboxylic acid).

We have studied the effects in three rodent models of generalised convulsive or absence epilepsy of two antagonists of group I metabotropic glutamate receptors that are selective for the mGlu1 receptor. LY 367385 ((+)-2-methyl-4-carboxyphenylglycine) and AIDA ((RS)-1-aminoindan-1,5-dicarboxylic acid) have been administered intracerebroventricularly (i.c.v.) to DBA/2 mice and lethargic mice (lh/lh), and focally into the inferior colliculus of genetically epilepsy prone rats (GEPR). In DBA/2 mice both compounds produce a rapid, transient suppression of sound-induced clonic seizures (LY 367385: ED50 = 12 nmol, i.c.v., 5 min; AIDA: ED50 = 79 nmol, i.c.v., 15 min). In lethargic mice both compounds significantly reduce the incidence of spontaneous spike and wave discharges on the electroencephalogram, from <30 to >150 min after the administration of AIDA, 500 nmol, i.c.v., and from 30 to >150 min after the administration of LY 367385, 250 nmol, i.c.v. LY 367385, 50 nmol, suppresses spontaneous spike and wave discharges from 30 to 60 min. In genetically epilepsy prone rats both compounds reduce sound-induced clonic seizures. LY 367385, 160 nmol bilaterally, fully suppresses clonic seizures after 2-4 h. AIDA is fully effective 30 min after 100 nmol bilaterally. It is concluded that antagonists of mGlu1 receptors are potential anticonvulsant agents and that activation of mGlu1 receptors probably contributes to a variety of epileptic syndromes.

Is ataxic gait the predominant presenting manifestation of Creutzfeldt-Jakob disease? Experience of 14 Chinese cases from Taiwan.

Creutzfeldt-Jakob disease (CJD) is caused by an unusual prion protein. Rare CJD cases have been reported in Chinese individuals. This report describes the clinical manifestations of 14 Chinese individuals with clinically definite CJD from the National Taiwan University Hospital during the period 1976-1995. It is the largest case series of Chinese CJD up to now. All these patients fulfil the clinical definite diagnosis of CJD proposed by Brown et al. (1986), including rapidly evolving dementia, myoclonus, periodic electroencephalographic (EEG) activity (0.5-2 Hz) and death within 12 months. The clinical characteristics of the present series, including age at onset, sex ratio, duration, initial symptoms, neurological signs, EEG abnormalities, and neuroimaging studies were similar to those reported in other countries. However, there is a high incidence of initial ataxic gait as the presentation in our patients. Eight (57%) out of 14 patients initially had gait ataxia alone or in association with dementia. CJD should be considered in the differential provisional diagnosis of any middle-aged patient with a progressive ataxic syndrome.

Subtypes and case-fatality rates of stroke: a hospital-based stroke registry in Taiwan (SCAN-IV).

Stroke data bank can afford important information regarding risk factors, pathogenesis, prognosis, etc. By means of hospital-based stroke registry, we investigated the risk factors and case-fatality rates in different types of stroke and transient ischemic attack (TIA) patients at the National Taiwan University Hospital in 1995. After excluding ineligible patients, 995 patients aged 1-98 years (575 men and 420 women) were recruited. Men predominated in all age groups for stroke and TIA in general except for cerebral hemorrhage (CH) in patients aged < 35 years and subarachnoid hemorrhage (SAH) in patients aged > or = 45 years. Of these, 676 (67.9%), 41 (4.1%), 228 (22.9%) and 50 (5%) patients were classified in the categories of cerebral infarction (CI), TIA, CH and SAH, respectively. The CI/CH ratio was 2.96. Hypertension remained one of the most important risk factors for CI, CH and TIA patients. Severe extracranial carotid artery stenosis (> or = 50%) was found in 12% of the CI patients and 27% of the TIA patients, but not found in the CH and SAH patients. Of these patients, the 30-day case-fatality rate was 10.9%, highest in SAH (30%), followed by CH (24.1%) and CI (5.6%). There were 41 in-hospital stroke patients who had significantly higher case-fatality rates than the other stroke patients (P<0.001 for all stroke, CI and CH patients by chi2 test). As compared to the previous stroke registries in Taiwan, there is a secular trend of increasing CI/CH ratios. These findings in Taiwan were compared with those in other populations, including other Asian, Caucasian and black populations. The CI/CH ratios in Asian populations, including Chinese, Japanese and Korean, were much lower than those in Caucasian and black populations. Dietary, environmental and genetic factors probably play important roles in these differences.

Changes in hemodynamics of the carotid and middle cerebral arteries before and after endoscopic sympathectomy in patients with palmar hyperhidrosis: preliminary results.

OBJECT: The purpose of this study was to analyze the change in carotid and middle cerebral artery (MCA) hemodynamics before and after endoscopic upper thoracic sympathectomy in patients with palmar hyperhidrosis (PH). METHODS: Sixty-eight patients with PH (35 males and 33 females) for whom the average age was 24.5+/-10.7 years (+/- standard deviation) were recruited into this study. These patients all underwent routine upper T-2 sympathectomy to treat their PH. Ultrasonography studies of the carotid arteries (CAs) and MCA were obtained in each patient before and after T-2 sympathectomy. The blood flow volume, flow velocity, and resistivity index (RI) in the bilateral common CAs (CCAs), internal CAs (ICAs), and external CAs (ECAs) were evaluated using duplex ultrasonography. The systolic peak velocity, mean velocity, diastolic peak velocity, pulsatility index, and RI of the bilateral MCAs were evaluated using transcranial Doppler ultrasonography. Blood pressure and heart rate were also recorded during this study. The Student paired t-test was used to analyze the differences between studies before and after bilateral T-2 sympathectomy. There was a significant reduction in diastolic pressure after T-2 sympathectomy (p = 0.003), but not in systolic pressure or heart rate. The vessel diameter was increased after sympathectomy in the left CAs and right CCA. The T-2 sympathectomy led to significant elevation of blood flow volume and RI in the left CCA, ICA, and ECA (p < 0.05). The authors found significant increases in maximum flow velocity and RI in the left MCA (p < 0.05). CONCLUSIONS: Patients who underwent T-2 sympathectomy demonstrated a significant increase in blood flow volume and flow velocities of the CAs and MCA, especially on the left side. Asymmetry of sympathetic influence on the hemodynamics of the CAs and MCA was noted. The usefulness of sympathectomy for the treatment of ischemic cardiovascular and cerebrovascular disease deserves further investigation.

Spontaneous oscillations of cerebral blood flow velocity in the middle cerebral arteries of normal subjects and schizophrenic patients.

Although many regional cerebral blood flow (rCBF) studies of schizophrenic patients have been carried out, only a few studies have investigated real-time hemodynamic changes in schizophrenic patients. In the present study, we used long-term monitoring of the middle cerebral artery (MCA) by non-invasive transcranial Doppler ultrasonography to obtain real-time CBF data in 55 schizophrenic patients and 20 normal comparison subjects. The mean blood flow velocity and pulsatility index (PI) of the MCA were not constant during long-term monitoring. They showed sinusoidal oscillations similar to those described in previous reports. The amplitude variations of these oscillations in both drug-naive and medicated schizophrenic patients were significantly decreased compared with findings in normal control subjects. The averaged PI values were found to be decreased in patients with illness durations of more than 10 years. After withdrawal of antipsychotic medication, both the amplitude variations of oscillations and the PI values in the drug-withdrawn patients were significantly decreased relative to findings in normal control subjects. Our results show a decreased adjustment ability of cerebral vessel resistance not only in neuroleptic-naive schizophrenic patients but also in patients with longer illness duration. Neuroleptics could affect the adjustment ability of vessel resistance.

Diagnosis and follow-up of carotid-cavernous fistulas by carotid duplex sonography and transcranial color Doppler imaging.

To investigate the suitability of extracranial carotid duplex (ECD) and transcranial color Doppler imaging (TCDI) in the diagnosis and follow-up of treatment in patients with carotid-cavernous fistulas (CCF), combined ECD and TCDI examinations were studied in seven patients with traumatic CCF. According to angiography, four patients had direct CCF, two indirect CCF and one both direct and indirect CCF. In ECD, hemodynamic parameters of the feeding artery showed an abnormally increased flow volume and decreased resistivity indices in five direct CCFs from the internal carotid artery and one indirect CCF from the external carotid artery. Direct visualization of the CCF was achieved in patients with direct CCF only, and revealed itself as a heterogeneous mosaic flash resulting from high flow velocities and turbulence. Patterns of venous drainage were detected via the transorbital and transforaminal windows in seven and five patients (four direct and one indirect CCF patients), respectively. These abnormal findings were improved or even normalized after successful treatment. In conclusion, combined ECD and TCDI examinations appear to be useful for the diagnosis and follow-up of CCF.

Cerebral venous thrombosis in patients with nephrotic syndrome--case reports.

The authors describe two cases of cerebral venous thrombosis (CVT) in patients with nephrotic syndrome. The main clinical features of CVT were persistent headache, hemiparesis, and seizure, and the diagnosis was based on magnetic resonance imaging and magnetic resonance angiography. Both showed acquired deficiency of free protein S. The neurologic symptoms remained stationary in the first patient, who received no anticoagulation therapy, but resolved rapidly in the second, treated with intravenous heparin and supplemented with fresh frozen plasma. CVT should be suspected in patients with nephrotic syndrome who present with symptoms of intracranial hypertension or any focal neurologic deficit.

Reverse jugular flow in a case of thrombosis of the brachiocephalic vein with an artificial arteriovenous fistula.

Thrombosis of the thoracic inlet veins following placement of a central venous catheter is a well-known complication, and several findings have been reported by color Doppler sonography. However, reverse jugular flow resulting from this complication is rarely mentioned and should be differentiated from another complication of iatrogenic arteriovenous fistula between neck vessels. The authors here describe a uremic patient with an artificial arteriovenous fistula in the forearm complicated with thrombosis of the ipsilateral brachiocephalic vein. Factors permitting the differential diagnosis by coloer Doppler sonography and clinical conditions are proposed.

Effects of mild whole body hyperthermia on graded focal ischaemia-reperfusion in a rat stroke model.

The influence of body temperature on focal cerebral ischaemia-reperfusion was investigated by using a well established rat stroke model. Three different degrees of ischaemia were created in the cerebral cortex of the right middle cerebral artery territory by varying the duration of clamping of the bilateral common carotid arteries and the right middle cerebral artery with full reperfusion. Mild hyperthermic (body temperature 38-39 degrees C) influence during ischaemia significantly enhanced the severity of infarction in mild (30 min) ischaemia, mean infarct volume was 78% greater than normothermic (body temperature 36.5-37.5 degrees C) group (P < 0.001); and in moderate (60 min) ischaemia, mean infarct volume was 23% greater than in the normothermic group (P < 0.05); but no difference between the two groups was observed in severe (90 min) ischaemia. Our data suggest that mild whole body hyperthermia during focal ischaemia-reperfusion has a detrimental effect on the infarct volume only in mild and moderate ischaemia in this model.

Factor structure and explanatory variables of the Mini-Mental State Examination (MMSE) for elderly persons in Taiwan.

BACKGROUND AND PURPOSE: The Mini-Mental State Examination (MMSE) is commonly used in studies and clinical assessment of cognitive functioning. The purpose of this study was to examine the factor structure and variables explaining the scores of the MMSE in elderly persons in Taiwan, in order to provide a reference for instrument selection and data collection for clinicians and researchers. METHODS: Secondary data from an epidemiologic study that included 1,442 randomly selected subjects aged 64 to 98 with an average age of 72.6 years were used. Males comprised 57.1% of the sample, and females 42.9%. Exploratory and confirmatory factor analysis and covariance structure modeling were used to analyze the data. RESULTS: In the cross validation of the covariance structure modeling, 50.1% of the variance in simple processing, 86.9% in complex processing, and 66.9% in memory/attention were explained. Better education background predicted better score in complex processing ability (path coefficient = .860). Greater independence in self-care ability predicted better scores in simple processing (path coefficient = -.716) and memory/attention (path coefficient = -.811). CONCLUSION: The results of this study indicate that items in the MMSE measuring complex processing ability including writing, reading and obeying, and copy design are seriously biased by educational background, and that the remaining items are better indicators of the subject's cognitive functioning for elderly persons in Taiwan. In our model, self-care ability was strongly related to cognitive functioning as measured by the MMSE, especially for items in the factors of simple processing (registration, naming, repetition, and commanding) and attention/memory (orientation to place and time, attention, and recall).