Prediction of anesthetic torsadogenicity using a human ventricular cell model.

This simulation study was designed to predict the torsadogenicity of sevoflurane and propofol in healthy control, as well as type 1 and type 2 long QT syndrome (LQT1 and LQT2, respectively), using the O'Hara-Rudy dynamic model. LQT1 and LQT2 models were simulated by decreasing the conductances of slowly and rapidly activating delayed rectifier K+ currents (IKs and IKr, respectively) by 50%, respectively. Action potential duration at 50% repolarization level (APD50) and diastolic intracellular Ca2+ concentration were measured in epicardial cell during administration of sevoflurane (1 ~ 5%) and propofol (1 ~ 10 µM). Torsadogenicity can be predicted from the relationship between APD50 and diastolic intracellular Ca2+ concentration, which is classified by the decision boundary. Whereas the relationships in control and LQT1 models were distributed on nontorsadogenic side in the presence of sevoflurane at all tested concentrations, those in LQT2 models were shifted to torsadogenic side by concentrations of ≥ 2%. In all three models, propofol shifted the relationships in a direction away from the decision boundary on nontorsadogenic side. Our findings suggest that sevoflurane, but not propofol, exerts torsadogenicity in patients with reduced IKr, such as LQT2 patients. Caution should be paid to the occurrence of arrhythmia during sevoflurane anesthesia in patients with reduced IKr.

Severe Calcification of Femoral Arteries Causes Tourniquet Failure Accompanied by Massive Bleeding.

Tourniquet failure is attributed to inadequate tourniquet pressure, inadequate exsanguination, failure to compress medullary vessels within the bone, and incompressible calcified arteries. We herein report a case of massive bleeding using a properly functioning tourniquet in a patient who had bilateral calcified femoral arteries. When incompressible calcified arteries are present, the inflated tourniquet cuff fails to adequately compress the underlying artery, yet acts as an efficient venous tourniquet, which leads to an increase in bleeding. It is therefore critical to preoperatively confirm the effectiveness of the tourniquet in arterial occlusion in patients with severe arterial calcification.

Propofol, an Anesthetic Agent, Inhibits HCN Channels through the Allosteric Modulation of the cAMP-Dependent Gating Mechanism.

Propofol is a broadly used intravenous anesthetic agent that can cause cardiovascular effects, including bradycardia and asystole. A possible mechanism for these effects is slowing cardiac pacemaker activity due to inhibition of the hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels. However, it remains unclear how propofol affects the allosteric nature of the voltage- and cAMP-dependent gating mechanism in HCN channels. To address this aim, we investigated the effect of propofol on HCN channels (HCN4 and HCN2) in heterologous expression systems using a whole-cell patch clamp technique. The extracellular application of propofol substantially suppressed the maximum current at clinical concentrations. This was accompanied by a hyperpolarizing shift in the voltage dependence of channel opening. These effects were significantly attenuated by intracellular loading of cAMP, even after considering the current modification by cAMP in opposite directions. The differential degree of propofol effects in the presence and absence of cAMP was rationalized by an allosteric gating model for HCN channels, where we assumed that propofol affects allosteric couplings between the pore, voltage-sensor, and cyclic nucleotide-binding domain (CNBD). The model predicted that propofol enhanced autoinhibition of pore opening by unliganded CNBD, which was relieved by the activation of CNBD by cAMP. Taken together, these findings reveal that propofol acts as an allosteric modulator of cAMP-dependent gating in HCN channels, which may help us to better understand the clinical action of this anesthetic drug.

A Pure Acute Subdural Hematoma Presenting with a Diploic Arteriovenous Fistula: Case Report and Literature Review.

Objective: We report a case of pure acute subdural hematoma (SDH) caused by a diploic arteriovenous fistula (AVF) and it is a first case report as far as we researched it. Case Presentation: A 19-year-old man was admitted as an emergency to our hospital with headache and nausea. CT scan on hospital admission showed a right acute SDH. Because there was no history of head trauma, MRI, MRA, and DSA were performed to identify a source of bleeding. DSA disclosed an AVF. The shunt was located between a frontotemporal branch of the middle meningeal artery (MMA) and a diploic vein, and its shunting point formed an aneurysmal sac, which was considered to have ruptured. Endovascular treatment was administered rather than surgical treatment to prevent re-bleeding because the patient was conscious and alert, CT showed a small SDH, and the left MMA near the shunting point was accessible for catheterization. A diluted mixture of 25% n-butyl-2-cyanoacrilate was injected into a left frontoparietal branch just before the shunting point and the shunt, including the aneurysmal sac, was obliterated. The patient's postoperative course was uneventful and he was discharged without neurological deficits. Conclusion: We experienced a patient with a pure acute SDH caused by diploic AVF. In patients with non-traumatic acute SDH, DSA is recommended to determine its underlying cause. Our review of published reports yielded few instances of non-traumatic pure acute SDH in young people. Possible causative factors should be investigated promptly and appropriate treatment provided immediately.

Elevation of propofol sensitivity of cardiac IKs channel by KCNE1 polymorphism D85N.

BACKGROUND AND PURPOSE: The slowly activating delayed rectifier K+ channel (IKs ), composed of pore-forming KCNQ1 α-subunits and ancillary KCNE1 ß-subunits, regulates ventricular repolarization in human heart. Propofol, at clinically used concentrations, modestly inhibits the intact (wild-type) IKs channels and is therefore unlikely to appreciably prolong QT interval in ECG during anaesthesia. However, little information is available concerning the inhibitory effect of propofol on IKs channel associated with its gene variants implicated in QT prolongation. The KCNE1 single nucleotide polymorphism leading to D85N is associated with drug-induced QT prolongation and therefore regarded as a clinically important genetic variant. This study examined whether KCNE1-D85N affects the sensitivity of IKs to inhibition by propofol. EXPERIMENTAL APPROACH: Whole-cell patch-clamp and immunostaining experiments were conducted in HEK293 cells and/or mouse cardiomyocyte-derived HL-1 cells, transfected with wild-type KCNQ1, wild-type or variant KCNE1 cDNAs. KEY RESULTS: Propofol inhibited KCNQ1/KCNE1-D85N current more potently than KCNQ1/KCNE1 current in HEK293 cells and HL-1 cells. Immunostaining experiments in HEK293 cells revealed that pretreatment with propofol (10 µM) did not appreciably affect cell membrane expression of KCNQ1 and KCNE1 proteins in KCNQ1/KCNE1 and KCNQ1/KCNE1-D85N channels. CONCLUSION AND IMPLICATIONS: The KCNE1 polymorphism D85N significantly elevates the sensitivity of IKs to inhibition by propofol. This study detects a functionally important role of KCNE1-D85N polymorphism in conferring genetic susceptibility to propofol-induced QT prolongation and further suggests the possibility that the inhibitory action of anaesthetics on ionic currents becomes exaggerated in patients carrying variants in genes encoding ion channels.

Positive Inotropic Effects of ATP Released via the Maxi-Anion Channel in Langendorff-Perfused Mouse Hearts Subjected to Ischemia-Reperfusion.

The organic anion transporter SLCO2A1 constitutes an essential core component of the ATP-conductive large-conductance anion (Maxi-Cl) channel. Our previous experiments using Langendorff-perfused mouse hearts showed that the Maxi-Cl channel contributes largely to the release of ATP into the coronary effluent observed during 10-min reperfusion following a short period (6 min) of oxygen-glucose deprivation. The present study examined the effect of endogenous ATP released via Maxi-Cl channels on the left ventricular contractile function of Langendorff-perfused mouse hearts, using a fluid-filled balloon connected to a pressure transducer. After the initial 30-min stabilization period, the heart was then perfused with oxygen-glucose-deprived Tyrode solution for 6 min, which was followed by a 10-min perfusion with oxygenated normal Tyrode solution in the absence and presence of an ATP-hydrolyzing enzyme, apyrase, and/or an adenosine A1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). In the absence of apyrase and DPCPX, the left ventricular developed pressure (LVDP) decreased from a baseline value of 72.3 ± 7.1 to 57.5 ± 5.5 mmHg (n = 4) at the end of 6-min perfusion with oxygen-glucose-deprived Tyrode solution, which was followed by a transient increase to 108.5 ± 16.5 mmHg during subsequent perfusion with oxygenated normal Tyrode solution. However, in the presence of apyrase and DPCPX, the LVDP decreased to the same degree during 6-min perfusion with oxygen-glucose-deprived Tyrode solution, but failed to exhibit a transient increase during a subsequent perfusion with oxygenated normal Tyrode solution. These results strongly suggest that endogenous ATP released through Maxi-Cl channels contributes to the development of transient positive inotropy observed during reperfusion after short-period hypoxia/ischemia in the heart.

A computational analysis of the effect of sevoflurane in a human ventricular cell model of long QT syndrome: Importance of repolarization reserve in the QT-prolonging effect of sevoflurane.

The slowly and rapidly activating delayed rectifier K+ channels (IKs and IKr, respectively) contribute to the repolarization of ventricular action potential in human heart and thereby determine QT interval on an electrocardiogram. Loss-of-function mutations in genes encoding IKs and IKr cause type 1 and type 2 long QT syndrome (LQT1 and LQT2, respectively), accompanied by a high risk of malignant ventricular arrhythmias and sudden cardiac death. This study was designed to investigate which cardiac electrophysiological conditions exaggerate QT-prolonging and arrhythmogenic effects of sevoflurane. We used the O'Hara-Rudy dynamic model to reconstruct human ventricular action potential and a pseudo-electrocardiogram, and simulated LQT1 and LQT2 phenotypes by decreasing conductances of IKs and IKr, respectively. Sevoflurane, but not propofol, prolonged ventricular action potential duration and QT interval in wild-type, LQT1 and LQT2 models. The QT-prolonging effect of sevoflurane was more profound in LQT2 than in wild-type and LQT1 models. The potent inhibitory effect of sevoflurane on IKs was primarily responsible for its QT-prolonging effect. In LQT2 model, IKs was considerably enhanced during excessive prolongation of ventricular action potential duration by reduction of IKr and relative contribution of IKs to ventricular repolarization was markedly elevated, which appears to underlie more pronounced QT-prolonging effect of sevoflurane in LQT2 model, compared with wild-type and LQT1 models. This simulation study clearly elucidates the electrophysiological basis underlying the difference in QT-prolonging effect of sevoflurane among wild-type, LQT1 and LQT2 models, and may provide important information for developing anesthetic strategies for patients with long QT syndrome in clinical settings.

Open-channel blocking action of volatile anaesthetics desflurane and sevoflurane on human voltage-gated Kv 1.5 channel.

BACKGROUND AND PURPOSE: Volatile anaesthetics have been shown to differentially modulate mammalian Shaker-related voltage-gated potassium (Kv 1.x) channels. This study was designed to investigate molecular and cellular mechanisms underlying the modulatory effects of desflurane or sevoflurane on human Kv 1.5 (hKv 1.5) channels. EXPERIMENTAL APPROACH: Thirteen single-point mutations were constructed within pore domain of hKv 1.5 channel using site-directed mutagenesis. The effects of desflurane or sevoflurane on heterologously expressed wild-type and mutant hKv 1.5 channels were examined by whole-cell patch-clamp technique. A computer simulation was conducted to predict the docking pose of desflurane or sevoflurane within hKv 1.5 channel. KEY RESULTS: Both desflurane and sevoflurane increased hKv 1.5 current at mild depolarizations but decreased it at strong depolarizations, indicating that these anaesthetics produce both stimulatory and inhibitory actions on hKv 1.5 channels. The inhibitory effect of desflurane or sevoflurane on hKv 1.5 channels arose primarily from its open-channel blocking action. The inhibitory action of desflurane or sevoflurane on hKv 1.5 channels was significantly attenuated in T480A, V505A, and I508A mutant channels, compared with wild-type channel. Computational docking simulation predicted that desflurane or sevoflurane resides within the inner cavity of channel pore and has contact with Thr479, Thr480, Val505, and Ile508. CONCLUSION AND IMPLICATIONS: Desflurane and sevoflurane exert an open-channel blocking action on hKv 1.5 channels by functionally interacting with specific amino acids located within the channel pore. This study thus identifies a novel molecular basis mediating inhibitory modulation of hKv 1.5 channels by desflurane and sevoflurane.

Transient Receptor Potential Canonical Channel Blockers Improve Ventricular Contractile Functions After Ischemia/Reperfusion in a Langendorff-perfused Mouse Heart Model.

Reperfusion of ischemic myocardium is accompanied by intracellular Ca overload, leading to cardiac dysfunction. However, the mechanisms underlying intracellular Ca overload have yet to be fully elucidated. The mechanism may involve the activation of store-operated Ca entry, which is primarily mediated through the transient receptor potential canonical (TRPC) channels. This study was undertaken to examine the possible involvement of TRPC channels in the development of contractile dysfunction associated with reperfusion of ischemic myocardium using a mouse heart model. The functional expression of TRPC channels was confirmed in mouse ventricular myocytes using immunocytochemistry, Western blotting, and patch-clamp experiments. The left ventricular functions were assessed by measuring left ventricular end-diastolic pressure, left ventricular developed pressure, and its first derivatives in a Langendorff-perfused mouse heart subjected to 30 minutes of normothermic (37°C) global ischemia followed by 60 minutes of reperfusion. Under control conditions, left ventricular functions were deteriorated during reperfusion, which was significantly ameliorated by administration of the TRPC channel blockers 2-aminoethoxydiphenyl borate and La during initial 5 minutes of reperfusion. Our findings suggest that TRPC channels are involved in mediating contractile dysfunction during reperfusion of ischemic myocardium and detect TRPC channels as a potential therapeutic target for preventing myocardial ischemia/reperfusion injury.

Interactions of Propofol With Human Voltage-gated Kv1.5 Channel Determined by Docking Simulation and Mutagenesis Analyses.

Propofol blocks the voltage-gated human Kv1.5 (hKv1.5) channel by preferentially affecting in its open state. A previous mutational study suggested that several amino acids within the pore region of the hKv1.5 channel are involved in mediating the blocking action of propofol. The present investigation was undertaken to elucidate the predicted binding modes of propofol within the pore cavity of the open-state hKv1.5 channel, using computational docking and mutagenesis approaches. The docking simulation using a homology model of the hKv1.5 channel, constructed based on the crystal structure of the Kv1.2 channel, predicted that propofol was positioned at the base of the pore cavity of hKv1.5 channel, adjacent to 4 amino acids Thr479, Thr480, Val505, and Ile508, and formed arene-H interactions with Val505. The patch-clamp experiments on wild-type and mutant hKv1.5 channels constructed by site-directed mutagenesis revealed that the blocking potency of propofol was significantly reduced in T480A, V505A, and I508A but not in T479A mutants compared with wild-type hKv1.5 channel. These computational docking and experimental mutational analyses suggest that propofol is positioned at the base of the pore cavity and forms functional contact with Thr480, Val505, and Ile508 to directly block the hKv1.5 channel.

[Ruptured Dissecting Aneurysm of M2 Portion of the Middle Cerebral Artery:A Case Report].

A 71-year-old woman presented with a sudden onset of headache and vomiting. Computed tomography(CT)showed diffuse subarachnoid hemorrhage(SAH)that was more severe on the right side. Three-dimensional CT angiography and right carotid angiography(CAG)demonstrated 2-mm microaneurysms at the middle cerebral artery(MCA)bifurcation and anterior communicating artery, with slight narrowing and dilatation of the M2 inferior trunk. Each microaneurysm was smooth, making it difficult to identify the bleeding source. Thus, surgery was postponed at the acute stage, and further investigation was planned. Repeated CAG was diagnostically unsuccessful, finding no source of the bleeding. On day 45 after the onset, exploratory craniotomy was performed to confirm the cause of the SAH. During the operation, both microaneurysms were found to be unruptured. However, the distal portion of the M2 inferior trunk was dark purplish and red and enlarged in a fusiform shape, suggesting a dissecting aneurysm. Residue of the SAH observed near the enlarged vessel identified it as the bleeding source. The enlarged vessel was wrapped with Bemsheets, and the Bemsheets was clipped to secure it. A dissecting aneurysm of the distal MCA is rare, as is the onset of bleeding. Based on a review of the literature related to dissecting aneurysms of the distal MCA, we recommend exploratory craniotomy if CT demonstrates laterality of the sylvian fissure on the SAH and CAG reveals stenosis or occlusion of the distal MCA in cases of SAH for which no bleeding source is detected.

Hyperkalemia caused by rapid red cell transfusion and the potassium absorption filter.

We report a case of transient hyperkalemia during hysterectomy after cesarean section, due to preoperatively undiagnosed placenta accreta that caused unforeseen massive hemorrhage and required rapid red cell transfusion. Hyperkalemia-induced by rapid red cell transfusion is a well-known severe complication of transfusion; however, in patients with sudden massive hemorrhage, rapid red cell transfusion is necessary to save their life. In such cases, it is extremely important to monitor serum potassium levels. For an emergency situation, a system should be developed to ensure sufficient preparation for immediate transfusion and laboratory tests. Furthermore, sufficient stock of preparations to treat hyperkalemia, such as calcium preparations, diuretics, glucose, and insulin is required. Moreover, a transfusion filter that absorbs potassium has been developed and is now available for clinical use in Japan. The filter is easy to use and beneficial, and should be prepared when it is available.

Rare complication characterized by late-onset transient neurological symptoms without hyperperfusion after carotid artery stenting: A report of three cases.

We experienced a rare complication after carotid artery stenting (CAS) characterized by transient neurological symptoms with no evidence of distal emboli or hyperperfusion. Using neuroimaging, we investigated the pathogenesis of the complication that occurred after CAS in three patients who developed neurological symptoms over a period of ten hours after CAS and improved within two days. None of the three patients showed signs of fresh infarctions on diffusion-weighted imaging or hyperperfusion on single-photon emission computed tomography. However, high signal intensity was observed in the leptomeningeal zone of the cerebral hemisphere on the stent side in all three patients and in the leptomeningeal zone of the contralateral anterior cerebral artery territory in one patient. These areas were assessed using fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging without gadolinium administration. The high signal intensity in the leptomeningeal zone disappeared as the symptoms improved. Based on the transient nature of the neurological disorders and the normalization of FLAIR imaging findings in these patients, the pathogenesis of this complication might have been vasogenic edema due to vasoparalysis of the local vessels caused by the hemodynamic changes occurring after CAS.

[A case of ganglioglioma extended to the lateral ventricle and associated with neurofibromatosis type 1].

We encountered a rare case of intraventricular ganglioglioma associated with neurofibromatosis type 1. A 42-year-old woman presented with a feeling of heaviness of the head and dizziness. She was diagnosed with neurofibromatosis type 1 because she had multiple subcutaneous neurofibromas and café au lait spots. On admission, she deteriorated slightly(Japan Coma Scale 1)and suffered from cognitive dysfunction and right hemiparesis. A computed tomography(CT)scan showed that she had an obstructed hydrocephalus with a long and circular mass lesion, 2cm in diameter, in the anterior horn of the left lateral ventricle. The mass showed low signal intensity(SI)on the T1-weighted image(WI), heterogeneous high SI on the T2-WI, and dense enhancement on a Gd-DTPA contrast MRI, extending from the head of the left caudate nucleus to the lateral ventricle. The patient underwent an urgent operation via an anterior transcallosal approach because of an obstructed hydrocephalus. The tumor was removed in its entirety, including its origin at the caudate head. The pathological diagnosis was a ganglioglioma grade 1 according with the classification of the World Health Organization. Here we describe this case and discuss the rare association between gangliogliomas and neurofibromatosis type 1.

Rapid formation of cerebral microbleeds after carotid artery stenting.

BACKGROUND: Recent studies reported that cerebral microbleeds (CMBs), i.e. small areas of signal loss on T(2)*-weighted gradient-echo (GE) imaging, could develop rapidly after acute ischemic stroke. We hypothesized that CMBs rapidly emerge after carotid artery stenting (CAS). OBJECTIVE: We investigated the frequency of and predisposing factors for CMBs after CAS. METHODS: We retrospectively examined MRI before and after CAS in 88 consecutive patients (average age: 71.7 ± 7.2 years, average rates of carotid stenosis: 72.6 ± 12.8%) who underwent CAS for carotid artery stenosis between March 1, 2009, and September 30, 2010. We defined new CMBs as signal losses that newly appeared on the follow-up GE. We examined the association of new CMBs with demographics, risk factors, and baseline MBs. RESULTS: Among 88 patients, 18 (20.5%) had CMBs initially, and 7 (8.0%) developed new CMBs right after CAS. New CMBs appeared on the same side of CAS in all of the 7 patients. New CMBs appeared significantly more frequently in the CMB-positive group than in the CMB-negative one (22% vs. 4%, p = 0.03) on the pre-CAS MRI. Multivariate analysis also revealed that the presence of CMBs before CAS was an independent predictor of new development of CMBs after CAS (odds ratio: 8.09, 95% confidence interval: 1.39-47.1). CONCLUSION: CMBs can develop rapidly after CAS, especially in patients with pre-existing CMBs. Since the existence of CMBs prior to CAS suggests a latent vascular damage which is vulnerable to hemodynamic stress following CAS, particular attention should be paid to the prevention of intracerebral hemorrhage due to hyperperfusion after CAS.

Surgical strategy for intracranial endodermal cyst--case report.

Two cases of endodermal cyst of the posterior fossa are reported. A 12-year-old girl presented with severe headache and vomiting caused by increased intracranial pressure. Computed tomography and magnetic resonance (MR) imaging showed a cystic mass occupying the ambient and quadrigeminal cisterns. A 65-year-old woman presented with dizziness, and MR imaging revealed a cystic mass in the posterior fossa. The two patients underwent surgery for decompression and resection of the cyst. Surgical specimens of the cyst walls consisted of a single layer of ciliated columnar epithelium. The diagnoses were endodermal cyst. The optimal surgical goal is total resection of the cyst wall, but the cyst wall sometimes tightly adheres to the adjacent nerves, vessels, and vital structures. The cyst must communicate adequately with the surrounding cerebrospinal fluid space, and a newly closed cyst space must be avoided, by the widest possible resection of the cyst wall.

[A case of herpetic meningoencephalitis associated with massive intracerebral hemorrhage during acyclovir treatment: a rare complication].

We report a case of a 35-year-old female with herpetic meningoencephalitis confirmed by polymerase chain reaction and immunohistochemical study for herpes simplex virus-1 accompanied with a massive intracerebral hematoma as a complication. A hematoma localized at the medial temporal lobe and the medial frontal lobe occurred on the 11th day after initiation of acyclovir treatment. She subsequently required emergency surgery for temporal lobectomy, as well as hematoma and external decompression. Intracerebral hematoma with MR imaging showed gyral pattern along the cortex of the medial temporal lobe and the base of the medial frontal lobe. We speculate that the hemorrhage occurred by rupture of small vessels affected by vasculitis in addition to hypertension caused by increased intracranial pressure. We therefore emphasize the risk of intracerebral hemorrhage at an early stage or during acyclovir treatment, especially during one or two weeks after initiation of the treatment, and the necessity of careful observation during these periods.

The course of the lesser petrosal nerve on the middle cranial fossa.

OBJECTIVE: The course of the lesser petrosal nerve is not well understood and may be confused with the course of the greater petrosal nerve during middle fossa surgery. The objective was to examine the course of the lesser petrosal nerve along the floor of the middle cranial fossa from the region of the geniculate ganglion to its outlet from the skull base. There are no studies focused on the course of this nerve in relationship to the floor of the middle cranial fossa. METHODS: Twenty middle fossae from adult cadaveric specimens were examined using 3 to 40x magnification. RESULTS: The lesser petrosal nerve was partially exposed on the floor of the middle fossa without drilling in 75% of the middle fossae and totally covered by thin bone in 25%. It crossed the floor anterior to the greater petrosal nerve and exited the middle fossa through the canaliculus innominatus in 14 cases, foramen spinosum in 3 cases, and the sphenopetrosal suture in 3 cases. The course of the lesser petrosal nerve has been shown in textbooks to be parallel to the greater petrosal nerve. However, the lesser and greater petrosal nerves diverged in the area medial to the geniculate ganglion in 90% of middle fossae with the angle of divergence averaging 11.6 degrees. The course of the lesser petrosal nerve was divided into three patterns based on the site of confluence of the three bundles of fibers forming the nerve. CONCLUSION: The relationships of the lesser petrosal nerve in the middle cranial fossa have been described. An understanding of these relationships will reduce the likelihood of it being confused with the greater petrosal nerve during surgical approaches to the middle fossa.

[Superior sagittal sinus thrombosis caused by Crohn's disease and macrocytic anemia : a case report].

A 32-years-old man with a past history of hemorrhoids presenting with hemiparesis was diagnosed as having sagittal sinus thrombosis with hemorrtagic infarction. Laboratory data revealed macrocytic anemia (Hb 11.2 g/d/) with hypoproteinernia (5.5 g/d). After discharge the patient developed abdominal pain, diarrhea, edema in the leg and sustained anemia. Final diagnosis through colon fiberscope findings was Crohn's disease Macrocytic anemia seemed to be induced by Vit. B12 deficiency due to malabsorption. The mechanism and causal relationship between Crohn's disease and sinus thrombosis is discussed.