Idiopathic Internal Thoracic Artery (ITA) Pseudoaneurysm treated with Endovascular Embolization.

A 44-year-old female was diagnosed with an ITA pseudoaneurysm in the right supraclavicular fossa. She was successfully treated with endovascular embolization. The challenges of diagnosis and treatment are discussed.

Cerebral hemodynamics and baroreflex sensitivity after carotid artery stenting.

OBJECTIVES: The long-term hemodynamic effects of carotid angioplasty and stenting (CAS) are unclear. We performed a longitudinal study to investigate the variations in cerebral hemodynamics in patients undergoing CAS. MATERIALS AND METHODS: We performed prospective evaluation of 63 symptomatic male patients (19 patients had transient ischemic attack and 44 had minor stroke; mean age: 77.3 ± 6.3 years [range: 51-86]). The mean blood flow velocities (MBFV) and pulsatility index (PI) of the middle cerebral arteries (MCA) on both sides were evaluated using transcranial color-coded Doppler (TCCD) ultrasonography. Cardiac autonomic activities were evaluated by measuring baroreflex sensitivity (BRS). All parameters were measured at baseline prior to CAS and at 1, 3, 6, and 12 months after CAS. RESULTS: The preoperative MBFV and PI of the ipsilateral MCA were significantly lower than those of the contralateral side. However, after CAS, MBFV in the ipsilateral MCA increased significantly until 2 weeks after stenting, after which the MBFV gradually decreased and remained stable for 1 year after CAS. Further, we observed a nonsignificant increase in MBFV in the contralateral MCA after CAS. In contrast to the MBFV, the BRS values decreased significantly 1 month after stenting and returned to baseline levels 6 months after CAS. CONCLUSIONS: Patients with CAS showed improved global cerebral hemodynamic status. However, the BRS did not normalize initially, and baseline value was achieved at 6 months after stenting.

Low Breast Conserving Surgery (BCS) rates in public hospitals in Malaysia: The effect of stage and ethnicity.

INTRODUCTION: Breast-conserving surgery (BCS) with radiation therapy is the procedure of choice for early-stage breast cancer. Survival and locoregional recurrence is non-inferior to mastectomy, with superior cosmetic and psycho-social outcomes. Differing health systems have demonstrated a wide variation in the rate of BCS. Little is known about the rate of BCS and factors influencing its practice in middle resource countries. This study aims to examine the BCS rates in Malaysia and to identify factors influencing its uptake. METHODOLOGY: This is a multi-centre, cross-sectional study involving the University of Malaya Medical Centre (UMMC), Queen Elizabeth II Hospital (QEH), and Tengku Ampuan Rahimah Hospital (TARH). Patients diagnosed with invasive breast cancer from January 2014 to December 2015 were included, excluding stromal cancers and lymphomas. Univariate and multivariate analyses identified factors influencing BCS. RESULTS: A total of 1005 patients were diagnosed with breast cancer in the allocated time frame. Excluding incomplete records and those who did not have surgery, 730 patients were analysed. Overall BCS rate was 32.9%. The BCS rate was highest at QEH (54.1%), followed by UMMC (29.5%), and TARH (17.4%). 16.9% had BCS after neoadjuvant therapy. Factors influencing BCS uptake included age, ethnic group, breast-surgeon led services, AJCC Stage, tumour size, HER-2 expression, and tumour grade. CONCLUSIONS: The rate of BCS in Malaysia is low. A wide variation of rate exists among the studied hospitals. Younger age, earlier AJCC stage, and the presence of a Breast sub-specialist surgeon, would make it more likely that the patient has her breast conserved.

Frequency domain analysis of cerebral blood flow velocity and its correlation with arterial blood pressure.

We applied frequency domain analysis to detect and quantify spontaneous fluctuations in the blood flow velocity of the middle cerebral artery (MCAFV). Instantaneous MCAFV of normal volunteers was detected using transcranial Doppler sonography. Spectral and transfer function analyses of MCAFV and arterial blood pressure (ABP) were performed by fast Fourier transform. We found the fluctuations in MCAFV, like ABP, could be diffracted into three components at specific frequency ranges, designated as high-frequency (HF, 0.15 to 0.4 Hz), low-frequency (LF, 0.04 to 0.15 Hz), and very low-frequency (VLF, 0.016 to 0.04 Hz) components. The HF and LF components of MCAFV exhibited high coherence with those of ABP, indicating great similarity of MCAFV and ABP fluctuations within the two frequency ranges. However, it was not the case for the VLF component. Transfer function analysis revealed that the ABP-MCAFV phase angle was frequency-dependent in the LF range (r = -0.79, P < 0.001) but not in the HF range. The time delay between LF fluctuations of ABP and those of MCAFV was evaluated as 2.1 seconds. We conclude that in addition to traditional B-wave equivalents, there are at least two different mechanisms for MCAFV fluctuations: the HF and LF fluctuations of MCAFV are basically secondary to those of ABP, and cerebral autoregulation may operate efficiently in LF rather than HF range. Frequency domain analysis offers an opportunity to explore the nature and underlying mechanism of dynamic regulation in cerebral circulation.

Spectral analysis of arterial blood pressure and cerebral blood flow velocity during supine rest and orthostasis.

This study evaluates the effect of orthostasis on the low frequency (LF, 0.04 to 0.15 Hz) fluctuations in the blood flow velocity of the middle cerebral artery (MCAFV) in relation to its arterial blood pressure (ABP) equivalent to further define and quantify this relationship in cerebrovascular regulation. Spectral analysis was performed on 22 healthy subjects during supine rest and head-up tilt. The power in the LF range can be used to quantify the LF fluctuations, and four types of LF power data could be obtained for each individual: LF power of supine MCAFV, LF power of supine ABP, LF power of tilt MCAFV, and LF power of tilt ABP. By comparing LF power of MCAFV with LF power of ABP, two power ratios could be generated to describe the flow-pressure relationship during supine rest and head-up tilt, respectively, supine power ratio (LF power of supine MCAFV/ LF power of supine ABP) and tilt power ratio (LF power of tilt MCAFV/ LF power of tilt ABP). In addition, an index for dynamic autoregulation in response to orthostasis can be calculated from these two power ratios (tilt power ratio/supine power ratio). The authors found that this index was dependent on the extent of orthostatic MCAFV changes, and the dependency could be mathematically expressed (r = 0.61, P = .0001), suggesting its involvement in cerebrovascular regulation. Moreover, these data further support the previous observation that the LF fluctuations of MCAFV might result from modulation of its ABP equivalent, and the modulation effect could be quantified as the power ratio (LF power of MCAFV/ LF power of ABP). These observations could be an important step toward further insight into cerebrovascular regulation, which warrants more research in the future.

Transfer function analysis of cerebral hemodynamics in patients with carotid stenosis.

This study evaluates the validity of the transfer function analysis of spontaneous fluctuations of arterial blood pressure (ABP) and blood flow velocity of the middle cerebral artery (MCAFV) as a simple, convenient method to assess human cerebral autoregulation in patients with carotid stenosis. Eighty-three consecutive patients with various degrees of carotid stenosis and 37 healthy controls were enrolled. The carotid stenosis was graded based on the diagnostic criteria of duplex ultrasound. Instantaneous bilateral MCAFV and ABP of all participants were assessed noninvasively using transcranial Doppler sonography and the servocontrolled infrared finger plethysmography, respectively. Spectral analyses of ABP and MCAFV were performed by fast Fourier transform. The fluctuations in ABP as well as in MCAFV were diffracted into three components at specific frequency ranges designated as high-frequency (HF; 0.15 to 0.4 Hz), low-frequency (LF; 0.04 to 0.15 Hz), and very low-frequency (VLF; 0.016 to 0.04 Hz). Cross-spectral analysis was applied to quantify the coherence, transfer phase, and magnitude in individual HF, LF, and VLF components. Transcranial Doppler CO2 vasomotor reactivity was measured with 5% CO2 inhalation. The LF phase angle (r=-0.53, P<0.001); magnitude of VLF (r=-0.29, P=0.002), LF (r=-0.35, P<0.001), and HF (r=-0.47, P<0.001); and CO2 vasomotor reactivity (r=-0.66, P<0.001) were negatively correlated with the severity of stenosis. Patients with unilateral high-grade (greater than 90% stenosis) carotid stenosis demonstrated significant reduction in LF phase angle (P<0.001) and HF magnitude (P=0.018) on the ipsilateral side of the affected vessel compared with their contralateral side. The study also revealed a high sensitivity, specificity, and accuracy using LF phase angle and HF magnitude to detect a high-grade carotid stenosis. A strong correlation existed between the LF phase angle and the CO2 vasomotor reactivity test (r=0.62, P<0.001), and the correlation between the HF magnitude and the CO2 vasomotor reactivity (r=0.44, P<0.001) was statistically significant as well. We conclude that transfer function analysis of spontaneous fluctuations of MCAFV and ABP could be used to identify hemodynamically significant high-grade carotid stenosis with impaired cerebral autoregulation or vasomotor reserve.

Synthesis and structure-activity studies of N,N'-diarylguanidine derivatives. N-(1-naphthyl)-N'-(3-ethylphenyl)-N'-methylguanidine: a new, selective noncompetitive NMDA receptor antagonist.

Diarylguanidines, acting as NMDA receptor ion channel site ligands, represent a new class of potential neuroprotective drugs. Several diarylguanidines structurally related to N,N'-di-o-tolylguanidine (DTG), a known selective sigma receptor ligand, were synthesized and evaluated in in vitro radioligand displacement assays, with rat or guinea pig brain membrane homogenates, using the NMDA receptor ion channel site specific radioligand [3H]-(+)-5(S)-methyl-10(R),11-dihydro-5H-dibenzo[a,d]cyclohepten-5 ,10- imine (MK-801, 3), and the sigma receptor-specific radioligand [3H]-di-o-tolylguanidine (DTG, 5). This paper presents the structure-activity relationships leading to novel tri- and tetrasubstituted guanidines, which exhibit high selectivity for NMDA receptor ion channel sites and weak or negligible affinity for sigma receptors. The in vitro binding results from symmetrically substituted diphenylguanidines indicated that compounds having ortho or meta substituents (with respect to the position of the guanidine nitrogen) on the phenyl rings showed greater affinity for the NMDA receptor ion channel site compared with para-substituted derivatives. Among the group of ring substituents studied for symmetrical diarylguanidines, an isopropyl group was preferred at the ortho position and an ethyl group was preferred at the meta position. Several unsymmetrical guanidines containing a naphthalene ring on one nitrogen atom and an ortho- or a meta-substituted phenyl ring on the second nitrogen atom, e.g., N-1-naphthyl-N'-(3-ethylphenyl)guanidine (36), showed a 3-5-fold increase in affinity for the NMDA receptor ion channel site and no change in sigma receptor affinity compared to the respective symmetrical counterparts. Additional small substituents on the guanidine nitrogen atoms bearing the aryl rings resulted in tri- and tetrasubstituted guanidine derivatives which retained affinity for NMDA receptor ion channel sites but exhibited a significant reduction in their affinities for sigma receptors. For example, N-1-naphthyl-N'-(3-ethylphenyl)-N'-methylguanidine (40) showed high affinity for the NMDA receptor ion channel site (IC50 = 36 nM vs [3H]-3) and low affinity for sigma receptors (IC50 = 2540 nM vs [3H]-5). Selectivity for the NMDA receptor ion channel sites over sigma receptors appears to be dependent upon the structure of the additional substituents on the guanidine nitrogen atoms bearing the aryl groups. Methyl and ethyl substituents are most preferred in the tri- and tetrasubstituted diarylguanidines. The trisubstituted guanidine, N-1-naphthyl-N'-(3-ethylphenyl)-N'-methylguanidine (40) and its close analogues showed good in vivo neuroprotection and are potential neuroprotective drug candidates for the treatment of stroke and other neurodegenerative disorders.

Growth of Japanese encephalitis virus in Culex tritaeniorhynchus cell cultures.

Ovarian cells from the mosquito Culex tritaeniorhynchus established in continuous tissue cultures have been found to support the growth of Japanese encephalitis virus with titers reaching as high as 10(7.36) MICLD50 per 0.03 ml. Virus-cell cultures were serially subcultured 60 times over 300 days and the virulence of the virus was determined after each passage. A gradual loss in virus titer was observed, with titers always higher in the medium than in the cells. Cytopathogenic effects were not observed in the infected cell cultures, either in primary or subsequent passages. However, the cell growth rate suggested that the cells may have been metabolically or mechanically damaged. The chromosome complement of the cells remained unchanged. Direct-fluorescent antibody studies during early and late passages revealed a loss in virus infectivity from chronically infected cells which may have been due to a gradual decrease in virus replication as the passages increased. The infectivity of virus particles, however, returned to previous levels after passage into fresh cell cultures. The loss of virus particles during serial passage may be correlated with the condition of the cells.

The serial hemostasis-related changes in patients with cerebral infarction: comparison between progressing and non-progressing stroke.

Serial determinations of beta-thromboglobulin (BTG), platelet factor 4 (PF4), fibrinopeptide A (FPA), antithrombin III (ATIII), protein C (PC), fibrin (ogen) degradation product (FDP), FDP D-dimer, activated partial thromboplastin time (APTT), prothrombin time (PT), and euglobulin lysis time (ELT) were performed in 18 patients with non-progressing stroke and 14 patients with progressing stroke in order to predict the development of progressing stroke. Increasing levels of BTG, PF4 and FDP with frequent fluctuation were noted in both kinds of stroke. Fluctuation of FPA levels was also noted but was less pronounced. PC levels were found to be slightly decreased with fluctuation but the mean was still in the lower normal limit. BTG, PF4 and PC all elevated at the time of deterioration of physical condition in patients with progressing stroke, whereas FPA had no definite change at that time. From our study, we conclude that both platelet activation and coagulation process do occur in both kinds of stroke. But the latter plays a minor role in the formation of thrombosis. The hemostasis change, especially concerning the thrombosis formation, probably plays a role in the development of progressing stroke, but we cannot predict their development even by the detections of the newly known molecular substances appearing in various steps of the hemostatic mechanism. Development of new tests for understanding the whole dynamic change of the thrombosis process is necessary for accurate prediction of the progressing stroke in the future.

Transorbital color Doppler flow imaging of the carotid siphon and major arteries at the base of the brain.

PURPOSE: To describe and evaluate an application of sonography, transorbital color Doppler flow imaging of the carotid siphon and major intracranial arteries, and to compare it with transtemporal color Doppler flow imaging. METHODS: The carotid siphon and major arteries at the base of the brain of 50 healthy volunteers were screened using the transorbital color Doppler flow sonography. These arteries were also studied by a transtemporal approach for comparison. In 5 volunteers, MR images in special inclination planes were obtained and compared with the transorbital color-coded Doppler flow images. RESULTS: The B-mode image of the orbit and intracranial anatomic structures, in addition to the color-coded flow images, provided an unambiguous identification of the carotid siphon and major intracranial arteries. The failure rate was lower when using the transorbital approach than when using the transtemporal approach in identifying the anterior cerebral artery (17% versus 32%). Color Doppler flow imaging using the transtemporal approach was better for the middle cerebral artery, whereas color Doppler flow imaging using the transorbital approach was better for the anterior cerebral artery (contralateral). The Doppler incident angles using the transorbital approach were better for the carotid siphon and anterior cerebral artery (contralateral). CONCLUSION: Transorbital color Doppler flow imaging, when used in conjunction with the transtemporal examination, can add information concerning the major arteries at the base of the brain.

Brain SPECT imaging with 99Tcm-hexamethylpropyleneamine oxime in the early detection of cerebral infarction: comparison with transmission computed tomography.

A new cerebral blood flow agent, 99Tcm-hexamethylpropyleneamine oxime (HM-PAO), was evaluated for early detection of acute cerebral infarction in conjunction with the transmission computed tomographic (CT) studies. The data from 22 cases were analysed. Results reveal that 99Tcm-HM-PAO enables the early detection of acute cerebral infarction prior to CT with rather proper depiction of the extent of physiological abnormality in the majority of patients. This promising result together with the lack of logistical problems will make 99Tcm-HM-PAO a useful and practical agent worldwide for diagnosing and managing acute cerebral infarction.

Surface modification of PCL-TCP scaffolds improve interfacial mechanical interlock and enhance early bone formation: an in vitro and in vivo characterization.

Pretreatment of polycaprolactone-20% tricalcium phosphate (PCL-TCP) scaffolds under alkaline conditions can be utilized to alter surface characteristics for enhanced early bone formation. PCL-TCP scaffolds were treated with sodium hydroxide (NaOH) at various time intervals (group A: untreated, group B: 3M NaOH for 48 h, and group C: 3M NaOH for 96 h). In vitro results showed a greater degree of physical changes in the NaOH-treated scaffolds (B and C) than the untreated group (A). Clearly, the NaOH-treated scaffolds showed an increased surface roughness than the untreated ones. A significantly large number of "channel-like" pits and greater average pit sizes were detected in groups B (14.51 +/- 10.9 microm) and C (20.27 +/- 14.3 microm); and absent in group A. In addition, treated scaffolds had a significant reduction of the water contact angle (40.9-58.2%). Favorably, the pore dimensions and scaffold rod thickness remained unchanged throughout the experiment. When implanted in the calvaria of rabbits, NaOH-treated scaffolds reported greater early matrix deposition and bone formation from scanning electron images and Micro-computed tomography analyses. In conclusion, pretreatment of PCL-TCP scaffolds with NaOH increases the wettability and surface area for initial matrix deposition and early bone ingrowth.

[Clinical investigation by transcranial Doppler sonography of the effect of norepinephrine on cerebral arterial blood velocity of normotensive males].

Transcranial Doppler (TCD) sonography is a new, non-invasive method for evaluation of the hemodynamics of cerebral circulation. Using a 2-MHz probe, the intracranial middle, posterior, vertebral and basilar arteries can be isolated easily to obtain parameters of systolic, diastolic, mean velocities and pulsatility index (PI). Changes of blood velocities and PI can assist evaluation of the condition of intracranial arterial spasm, dilatation and cerebral vascular resistance. The purpose of this study is to evaluate the hemodynamic effect of norepinephrine (NE) on cerebral circulation. Eighteen normotensive male healthy volunteers (mean age 42 years) were studied with TCD before and during NE infusion (13-16 micrograms/min). Results showed that systolic, diastolic and mean arterial pressure were increased significantly during NE infusion. Blood velocities of middle, posterior, vertebral and basilar arteries also increased markedly. Increased cerebral vascular resistance with elevation of PI was also noted in all of the persons studied. These findings provide evidence that NE infusion induces intracerebral vasospasm.

The influence of age on weight-bearing joint reposition sense of the knee.

Knee joint-position sensitivity has been shown to decline with increasing age, with much of the research reported in the literature investigating this age effect in non-weight-bearing (NWB) conditions. However, little data is available in the more functional position of weight-bearing conditions. The objective of this study was to identify the influence of age on the accuracy and nature of knee joint-position sense (JPS) in both full weight-bearing (FWB) and partial weight-bearing (PWB) conditions and to determine the effect of lower-extremity dominance on knee JPS. Sixty healthy subjects from three age groups (young: 20-35 years old, middle-aged: 40-55 years, and older: 60-75 years) were assessed. Tests were conducted on both the right and left legs to examine the ability of subjects to correctly reproduce knee angles in an active criterion-active repositioning paradigm. Knee angles were measured in degrees using an electromagnetic tracking device, Polhemus 3Space Fastrak, that detected positions of sensors placed on the test limb. Errors in FWB knee joint repositioning did not increase with age, but significant age-related increases in knee joint-repositioning error were found in PWB. It was found that elderly subjects tended to overshoot the criterion angle more often than subjects from the young and middle-aged groups. Subjects in all three age groups performed better in FWB than in PWB. Differences between the stance-dominant (STD) and skill-dominant (SKD) legs did not reach significance. Results demonstrated that for, normal pain-free individuals, there is no age-related decline in knee JPS in FWB, although an age effect does exist in PWB. This outcome challenges the current view that a generalised decline in knee joint proprioception occurs with age. In addition, lower-limb dominance is not a factor in acuity of knee JPS.

Trends in mortality from cerebrovascular disease in Taiwan.

The rate of decline in the age-adjusted death rate from cerebrovascular disease (CVD) in Taiwan is not as rapid as in the United States and Japan, and the trends of CVD mortalities have not decreased steadily during the period 1972-1983. A low record of hypertension regulation (5.0%-12.7%), a high proportion (47.1%) of stroke due to cerebral hemorrhage (by clinical assessment), and a high fatality rate (40.1%) for cerebral hemorrhage may account partially for the slower declining rate. A geographic difference in the downward trend of CVD death rate was observed in this period. Districts remote from the major cities have had the lowest decline in CVD death rate.

Functional voiding disorders in women.

From July 1986 to Dec 1987, 78 women complaining of frequency, urgency, dysuria and suprapubic discomfort were evaluated at our clinic. Their ages ranged from 20 to 68 (mean age: 38.2). The patients who were noted to have evidence of pyuria, neurological or gynecological abnormalities were excluded from the study. Urodynamic examinations including uroflowmetry, cystometry (CMG), urethral pressure profiles (UPP) and electromyography (EMG) of the external urethral sphincter were performed. The results revealed low flow rates in 56 patients (71.8%), non-relaxation of the external sphincter during voiding in 55 patients (70.5%), unstable bladder in 6 patients (7.7%) and a high maximal urethral closure pressure (MUCP) (greater than 80 cmH2O) in 44 patients (56.4%). The average volume of the cystometric capacity (250 +/- 86 ml) was decreased. The association between the low flow rate, non-relaxation of the external sphincter and a high MUCP was statistically significant. Urethral hypersensitivity has been recognized as being the major cause of these symptoms.