Lymphangiogenesis in myocardial remodelling after infarction.

AIMS: The lymphatic system is involved in fluid homeostasis of the cardiac interstitium, but lymphangiogenesis in myocardial remodelling has not previously been examined histopathologically. The aim was to investigate by D2-40 immunohistochemistry the sequential changes in lymphatic distribution in the process of myocardial remodelling after myocardial infarction (MI). METHODS AND RESULTS: Myocardial tissues in various phases of healing after MI were obtained from 40 autopsied hearts. D2-40+ lymphatic vessel density (LD) and CD34+ blood vessel density (BD) in the lesion were determined. BD decreased with advance of myocardial necrosis, subsequently increased at the early stage of granulation and thereafter decreased with the progression of scar formation. In contrast, lymphatic vessels were not detected in lesions with coagulation necrosis, and newly formed lymphatics first appeared in the early stages of granulation. A subsequent increase in LD was demonstrated in the late stages of granulation, and lymphatics remained up to the scar phase. Vascular endothelial growth factor-C was consistently expressed in viable cardiomyocytes around the lesion in all of these stages. CONCLUSION: In myocardial remodelling after MI, lymphangiogenesis lags behind blood vessel angiogenesis; newly formed lymphatics may be involved mainly in the maturation of fibrosis and scar formation through the drainage of excessive proteins and fluid.

The Reconstructions for Vertebral Artery Stenosis at the Origin. A Comparison between PTA and Surgical Reconstructions.

SUMMARY: To date in our hospital, surgical reconstructions and percutaneous transluminal angioplasty (PTA) were carried out in 168 patients with vertebral artery (VA) stenosis at the origin. In this article, we discuss the comparison between surgical reconstructions and PTA, especially regarding long term follow up, patency and complications. PTA is a less invasive treatment for VA stenosis at the origin than surgical reconstructions. However, restenosis after PTA occurred in 20% of the patients. On the other hand, restenosis after surgical reconstructions did not emerge even in long term follow up. An embolism after PTA occurred in 2.6% of the cases. However, the embolism occurred in only the first 10 patients of our series, after that there was no embolism. We concluded that PTA was the first choice for VA stenosis at the origin, if the angiogram did not reveal any PTA difficulty. If restenosis after PTA was performed, we selected surgical reconstruction for VA stenosis at the origin.

Suitable image parameters and analytical method for quantitatively measuring cerebral blood flow volume with phase-contrast magnetic resonance imaging.

The aim of this study was to determine suitable image parameters and an analytical method for phase-contrast magnetic resonance imaging (PC-MRI) as a means of measuring cerebral blood flow volume. This was done by constructing an experimental model and applying the results to a clinical application. The experimental model was constructed from the aorta of a bull and circulating isotonic saline. The image parameters of PC-MRI (repetition time, flip angle, matrix, velocity rate encoding, and the use of square pixels) were studied with percent flow volume (the ratio of actual flow volume to measured flow volume). The most suitable image parameters for accurate blood flow measurement were as follows: repetition time, 50 msec; flip angle, 20 degrees; and a 512 x 256 matrix without square pixels. Furthermore, velocity rate encoding should be set ranging from the maximum flow velocity in the vessel to five times this value. The correction in measuring blood flow was done with the intensity of the region of interest established in the background. With these parameters for PC-MRI, percent flow volume was greater than 90%. Using the image parameters for PC-MRI and the analytical method described above, we evaluated cerebral blood flow volume in 12 patients with occlusive disease of the major cervical arteries. The results were compared with conventional xenon computed tomography. The values found with both methods showed good correlation. Thus, we concluded that PC-MRI was a noninvasive method for evaluating cerebral blood flow in patients with occlusive disease of the major cervical arteries.

Experimental study of intracisternal administration of tissue-type plasminogen activator followed by cerebrospinal fluid drainage in the ultra-early stage of subarachnoid haemorrhage.

This experimental study evaluated the effect of intrathecal injection of tissue-type plasminogen activator followed by cisternal drainage in the ultra-early stage of aneurysmal subarachnoid haemorrhage to prevent vasospasm. Twenty Japanese white rabbits were divided into five groups. Either tPA (groups A, B, and E) or saline (groups C and D) was injected intrathecally 1 hour (groups A, B, C, and D) or 21 hours (group E) after the intrathecal injection of blood. Cerebrospinal fluid was drained 2, 4, and 6 hours after the intrathecal injection of blood (groups A, C, and E). On day 4, the angiographic caliber of the basilar artery in each group was as follows (mean +/- SD): A, 85.9 +/- 5.0%; B, 74.6 +/- 5.3%; C, 69.1 +/- 2.7%; D, 64.0 +/- 4.9%; E, 80.2 +/- 2.7% (compared with baseline). In the two groups in which CSF was drained (groups A and C), fibrinolysis with tPA significantly suppressed vasospasm. In the two groups treated with tPA (groups A and B), cisternal drainage significantly suppressed vasospasm. In the two groups treated with saline (groups C and D), however, cisternal drainage did not suppress vasospasm. Examination of the series of CSF samples (groups A and C) showed that fibrinolysis with tPA effectively cleared clots early. In the two groups treated with tPA and CSF drainage (groups A and E), early removal of subarachnoid clots reduced the degree of vasospasm. Early fibrinolysis with tPA and early removal of subarachnoid clots by drainage is effective for preventing vasospasm.

Embolization of cerebral arteriovenous malformations with cellulose acetate polymer. Histological study of the resected specimens.

SUMMARY: To test the usefulness of a cellulose acetate polymer(CAP) solution for brain arteriovenous malformations (AVMs), we analyzed the clinical and histological results of patients with AVMs embolized using CAP solution. We reviewed the cases of six patients with cerebral AVMs treated by embolization prior to surgical resection. We used two types of CAP solutions, CAP-M and CAP-L, which are mixtures of 250 mg of solid CAP and 1800 or 2250 mg of bismuth trioxide dissolved in 5.5 or 7.0 ml of dimethyl sulfoxide, respectively. All patients underwent surgical resection 1 to 37 days after the embolization procedure. Resected specimens were fixed in formalin and stained for light microscopic examination. Eighteen feeding vessels were embolized. The reduction rate of the nidus volume was between 20% and nearly 100%. Mild ischemic deficits occurred in one patients but there were no hemorrhagic complications related to the embolization procedures. All AVMs were completely resected by surgery. Direct inspection at surgery revealed that there was no apparent swelling or hematomas in the normal brain areas adjacent to the nidus, and the AVMs were soft enough to be easily retracted. The histological examinations disclosed no or mild inflammatory reactions within two weeks after embolization. The internal elastic lamina was preserved in every case. Recanalization of embolized vessels was not observed until 37 days after embolization. CAP solution is a safe and useful embolic agent for brain AVMs. Further study is needed to resolve the issue of recanalization.

Dissociation of early and late protective immunity to the nematode Nippostrongylus brasiliensis in Brown Norway and Fischer-344 rats.

Worm expulsion of, and IgE and interferon (IFN)-gamma responses to, Nippostrongylus brasiliensis were studied in 2 rat strains, Brown Norway (BN) and Fischer (F)-344. BN rats expelled the majority of worms by day 14 post-infection (p.i.) with approximately 6% of worms surviving for at least 3 weeks. In F-344 rats, worm expulsion was delayed by 2 days relative to that in BN, while the numbers of residual worms were significantly fewer than in BN, suggesting that different immune mechanisms are involved in early and late phases of immunity. Total serum IgE, as well as in vitro IgE production by mesenteric lymph node (MLN) cells, was increased 2 weeks p.i., the levels being markedly higher in BN than in F-344 rats. Serum rat mast cell protease II was also increased more significantly in BN than in F-344 rats. In contrast, production of IgG2a and IFN-gamma by MLN and spleen cells was found to be higher in F-344 than in BN rats. These results indicate that the early worm expulsion is correlated with the host IgE and mast cell responsiveness, whereas the persistence of infection in the late period may be controlled by different immune mechanisms.

Cysteine protease of the nematode Nippostrongylus brasiliensis preferentially evokes an IgE/IgG1 antibody response in rats.

Some cysteine proteases such as papain and those of mites and schistosomes have potent allergenic properties. To clarify the allergenicity of nematode cysteine proteases, the enzyme was purified from the intestinal nematode Nippostrongylus brasiliensis using cation exchange chromatography and gel filtration chromatography. The purified protease, of 16 kD and pI 8.5, showed maximum enzyme activity at pH 5.5 and substrate preference for Z-Phe-Arg-MCA. The specific inhibitors of cysteine protease leupeptin, iodoacetic acid, and E-64, completely suppressed the activity, indicating that the purified enzyme belongs to the cysteine protease family. Cysteine protease activity was found not only in somatic extract, but also in the excretory-secretory (ES) product of the nematode. When anti-cysteine protease immunoglobulin isotypes were examined in sera from rats infected with N. brasiliensis, a high level of IgG1 and a lower level of IgE antibody were detected. Depletion of IgG antibodies from the sera using protein G affinity columns resulted in a marked increase in reactivity of anti-cysteine protease IgE with the antigen, possibly due to the removal of competing IgG antibodies. In contrast to IgE and IgG1, production of anti-cysteine protease IgG2a was negligible. These results indicate that the nematode cysteine protease preferentially evokes an IgE/IgG1 antibody response.

Early treatment of subarachnoid hemorrhage after preventing rerupture of an aneurysm.

Twelve patients with Hunt and Hess neurological Grades III to V underwent thrombosis of aneurysms using cellulose acetate polymer within 23 hours of aneurysm rupture. On computerized tomography (CT), nine of these patients had difuse or localized thick subarachnoid blood clots, two had diffuse thin clots and one had intraventricular clots. Immediately after thrombosis, all patients were administered tissue plasminogen activator (TPA) through spinal or ventricular catheters. The pressure of the lumbar cerebrospinal fluid was maintained at 100 to 150 mm H2O. The TPA was given as multiple injections of 2 mg on Day 0 and 1 to 2 mg on the following 1 to 2 days. In two patients the second injection of TPA was not given because of severe brain damage resulting from the initial subarachnoid hemorrhage. Ten patients showed complete clearance of the cisternal clot on CT within 72 hours after thrombosis. Seven partially thrombosed aneurysms and five multiple aneurysms were clipped during delayed surgery. Only one patient experienced mild vasospasm as shown on the follow-up angiogram. Eight patients improved clinically and had a good recovery, two had severe disability, and two died. Urgent thrombosis of a ruptured aneurysm followed by immediate postthrombotic administration of TPA may be a safe and reasonable means of preventing vasospasm and improving patient outcome.

Prophylactic thrombosis to prevent new bleeding and to delay aneurysm surgery.

Six aneurysms in five patients with acute aneurysmal subarachnoid hemorrhages were treated with direct thrombosis using cellulose acetate polymer within 4 hours of rupture. The aneurysms involved the internal carotid and posterior communicating arteries (two patients), the anterior choroidal artery (one patient), the bifurcation of the basilar artery (one patient), and the middle cerebral artery (two patients). Four patients underwent aggressive volume expansion after direct thrombosis with cellulose acetate polymer. The aneurysms remained thrombosed until operations on the necks were performed 2 to 7 weeks after the subarachnoid hemorrhages. Three patients were given intrathecal tissue plasminogen activator. One patient, who remained at neurological Grade V, was not treated surgically and died from cardiac failure. Five aneurysms in the remaining four patients were successfully clipped. These preliminary data suggest that immediate aneurysmal thrombosis, then aggressive preoperative prophylactic volume expansion and/or administration of intrathecal tissue plasminogen activator, can help prevent new bleeding and reduce delayed cerebral ischemia in patients after aneurysmal subarachnoid hemorrhages.

Direct thrombosis of a pseudoaneurysm after obliteration of a carotid-cavernous fistula with cellulose acetate polymer: technical case report.

A 55-year-old man who suffered a head injury resulting in a left traumatic carotid-cavernous fistula was successfully treated with an intravascular detachable balloon. A pseudoaneurysm formed adjacent to the balloon. Seven months after the initial procedure, treatment with cellulose acetate polymer, a new liquid thrombotic material, occluded the pseudoaneurysm and preserved the internal carotid artery.

Selection and combination of techniques for treating spontaneous carotid-cavernous sinus fistulas.

Twenty-eight patients with spontaneous carotid-cavernous sinus fistulas (CCFs) were treated using a variety of techniques. Three of four patients with direct CCFs underwent intravascular embolization with a detachable balloon. Embolization with polyvinyl alcohol particles through an external carotid endoarterial route was used in six patients with indirect CCFs, and with ethylene-vinyl alcohol copolymer solution in two. Patients undergoing these conventional treatments, including embolization of the meningeal branches of the external carotid artery, had less satisfactory outcomes. The transvenous approach using minicoils through the inferior petrosal sinus was successful in eight patients. One patient treated using the transvenous approach using copper wire through the ophthalmic vein had worsening of visual acuity and field. Unsuccessful transvenous embolization in four patients required direct surgical exposure and embolization with spring coils. Spontaneous cures occurred in four patients. Direct CCFs with high flow rates were best treated with the detachable balloon or coil technique through a internal carotid endoarterial route. Indirect CCFs were best treated with the minicoil through the inferior petrosal sinus. If these techniques fail, direct surgical exposure allows placement of coils into the cavernous sinus.

Ribbon enchephalo-duro-arterio-myo-synangiosis for moyamoya disease.

In patients with advanced moyamoya disease, reconstructive surgery alone may not prevent the deterioration of blood flow in the territory of the anterior cerebral artery. These types of surgery include superficial temporal artery-to-middle cerebral artery anastomosis and encephalo-duro-arterio-myo-synangiosis (EDAMS). Bilateral encephalo-duro-arterio-synangiosis (EDAS) gradually reduced the transient ischemic attacks in one of our patients who experienced motor weakness in the left extremities. After surgery, however, persistent bilateral attacks still occurred in the patient's legs. In a subsequent maneuver, we inserted the pedicle of the galea on both sides into the interhemispheric fissure, which induced marked vascularization in the territory of the anterior cerebral artery, and the attacks disappeared. Since then, we have combined this "ribbon" technique with EDAMS to treat eight patients with moyamoya disease. Postoperative angiograms showed widespread collateral circulation on the ischemic brain surface in six patients undergoing ribbon EDAS or EDAMS. Postoperative measurements of cerebral blood flow revealed improved circulation in the frontal region in four patients. The clinical results were excellent in six patients, and good in one, and we lost follow-up in one. The ribbon EDAMS procedure is effective on moyamoya disease with symptomatic cerebral ischemia of the anterior circulation.

Cellulose acetate polymer thrombosis for the emergency treatment of aneurysms: angiographic findings, clinical experience, and histopathological study.

Cellulose acetate polymer solution is a liquid thrombotic material that hardens into the shape of an aneurysm into which it is injected. Therapy using this solution is a rapid technique that helps prevent the rupture of aneurysms, especially those that extravasate contrast material during angiography in the acute stage of subarachnoid hemorrhage. Using this polymer solution and an endovascular technique, we treated two patients who had aneurysms of the basilar and anterior communicating arteries with extravasation of contrast material during angiography a few hours after the initial subarachnoid hemorrhage. In one patient with an aneurysm of the anterior communicating artery, the aneurysm's wall was perforated with the catheter during neurointerventional procedures. In both patients, postoperative angiograms demonstrated obliteration of the aneurysmal dome, including the site of extravasation or perforation. The parent artery and surrounding perforating branches were preserved. Although we do not advocate aggressive therapy for patients who bleed during angiography, we pursued this therapy in these two patients because of the opportunity to introduce cellulose acetate polymer in an attempt to preserve the patients' lives. Unfortunately, both patients died. Histopathological studies performed at the time of autopsy demonstrated that the luminal surface of cellulose acetate polymer was covered with thrombus by 6 days after cellulose acetate polymer thrombosis. By 10 days, the thrombus had a prominent fibrin network, a concentrated plasma component, and few fibrocytes adhering to its luminal surface.(ABSTRACT TRUNCATED AT 250 WORDS)

Surgical treatment of moyamoya disease: operative technique for encephalo-duro-arterio-myo-synangiosis, its follow-up, clinical results, and angiograms.

Moyamoya syndrome is defined as the development of collateral anastomosis pathways at the base of the brain, associated with chronic progressive stenosis of the carotid fork. Both reconstructive vascular surgery and conservative strategies are used to treat this syndrome, but the latter cannot prevent the disease from progressing. We describe the procedure of encephalo-duro-arterio-myo-synangiosis (EDAMS), and report the results in 17 patients (28 sides) who underwent EDAMS. The clinical symptoms of moyamoya disease include transient ischemic attacks, reversible ischemic neurological deficits, stroke, seizures, Gerstmann's syndrome, involuntary movements, or mental retardation resulting from the lack of cerebral blood flow. The clinical results of EDAMS were poor in one patient, fair in two, good in five, excellent in eight, and fair on one side and excellent on the other side in one patient. Postoperative angiograms showed widespread collateral circulation on the ischemic brain surface in patients undergoing EDAMS.

Direct thrombosis of aneurysms with cellulose acetate polymer. Part II: Preliminary clinical experience.

The authors report the treatment of seven intracranial aneurysms in six patients with direct infusion of cellulose acetate polymer solution, a new liquid thrombotic material. These aneurysms were considered inoperable because of their size or location, or because of the patient's neurological condition. This material avoids the difficulties associated with balloon occlusion, and completely fills even irregularly shaped aneurysms. Cellulose acetate polymer solution hardens in about 5 minutes and remains solid once inside the aneurysm. Because this technique is less invasive than surgery, it can be used for high-risk patients in the acute stage of subarachnoid hemorrhage. Transient motor aphasia occurred in one patient. A small residual neck, which caused rebleeding 3 months after the treatment, remained in another patient. This article describes the new material, the procedure for direct thrombosis, and preliminary clinical results.

[Unbranched-site aneurysm of intracranial internal carotid artery].

Most intracranial saccular aneurysms arise from the angle between a parent vessel and an arterial branch. Saccular aneurysms without relation to any arterial branch are rare. During the last 24 years, 210 patients with intracranial internal carotid artery (ICA) aneurysms were directly operated on at our institution. We found eight saccular aneurysms arising from intracranial ICA without relation to any arterial branch. So we call them unbranched-site aneurysms of intracranial ICA, and describe their unique characteristics. Of the eight cases with unbranched-site aneurysm of intracranial ICA, three were men and five were women. The age ranged from 31 to 61 years with an average age of 48. Seven cases suffered a subarachnoid hemorrhage due to ruptured unbranched-site aneurysm, and the other case had been admitted to our department because of accompanying ruptured left internal carotid-posterior communicating aneurysm. All cases of unbranched-site aneurysm presented intraoperative and/or angiographic findings of arteriosclerosis, and five of the patients had a past history of hypertension. Of the four unbranched-site aneurysms at the C2 portion of ICA, two arose from the lateral wall, one arose from the superior wall and the other arose from the infero-lateral wall of ICA. Of the four unbranched-site aneurysms at the C1 portion of ICA, three arose from the superior wall and the other arose from the supero-medial wall of ICA. Radical operation was performed in all cases and intraoperative rupture occurred in two cases. It was suggested that arteriosclerotic change in the arterial wall, and local hemodynamic stress played important roles in the development of unbranched-site aneurysms of intracranial ICA.

[Intrathecal dissemination of meningiomas; a case report].

A case of the cytologically verified intrathecal dissemination of benign meningiomas was reported. A 36-year-old man was admitted to our hospital because trans-sphenoidal surgery was planned for the repair of CSF rhinorrhea caused by a recurrent pituitary adenoma. The CT scan demonstrated incidental multiple tumors spread throughout in the pontomedullary and ambient cisterns. The head and spinal MRI showed more than fifteen small tumors in the posterior fossa and the thoracic spinal canal. CSF cytology revealed benign fibroblastic or meningotheliomatous meningioma with whorl formation and psammoma body. Several comments were made on the mechanism of the intrathecal dissemination of the meningiomas.

Low-level infection with the nematode Nippostrongylus brasiliensis induces significant and sustained specific and non-specific IgE antibody responses in rats.

Specific and non-specific IgE antibody responses were studied in SD rats infected with between 5 and 2500 Nippostrongylus brasiliensis (NB) larvae. In rats with 2500 NB larvae, specific IgE antibody, measured by enzyme-linked immunosorbent assay (ELISA) using NB excretory/secretory substance as antigen, reached a peak at 4 weeks of infection and gradually declined. On the other hand, in rats infected with 10 or 100 NB larvae, specific IgE was induced at 4 weeks of infection and the level continued to rise until at least 8 weeks after infection. The level at 8 weeks was significantly higher in rats infected with 10 or 100 larvae than in rats infected with 2500 larvae. The results indicate that the low-level infection induced a much more sustained specific IgE response than that induced after heavy infection. However, the level of specific IgG was correlated with the dose of infection, and reached a plateau 6 weeks after infection. Total serum IgE increased significantly even in rats infected with five larvae, a dose which did not induce detectable specific IgE. The kinetics of the production of total IgE was different in rats with light and heavy infections. In rats infected with five or 10 larvae, total IgE increased slowly and reached a plateau 4 weeks after infection. On the other hand, rats infected with more than 500 larvae showed a remarkable rise in total IgE at 2 weeks of infection; this rise gradually declined thereafter. Six weeks after infection, total IgE levels were almost the same (2-3 micrograms/ml) in rats infected with 10-2500 NB larvae. These results show that low-level NB infection induces a significant and sustained specific and non-specific IgE response in rats.

Liquid-level sensor with optical fibers.

A liquid-level sensor, consisting of three optical fibers, is described. A light is projected onto an oil surface through a transmitting fiber. A receiving fiber picks up the light reflected from the oil surface. A reference fiber transmits the light from a light-emitting diode back and forth along the same path as that of the transmitting fiber and the receiving fiber. Division is accomplished by using the reflected signal and the reference signal, so it becomes possible to eliminate apparent distance variations that are due to the variations in light intensity, which may be caused by external forces and temperature changes. The distance range is 100 mm.

[Direct embolization with occluding spring embolus for large aneurysm and carotid-cavernous fistula].

The authors describe a technique using occluding spring emboli for direct obliteration of an unclippable large aneurysm, and carotid-cavernous fistula (CCF) which failed to be occluded by transarterial and transvenous approaches. Case 1: This 44 year-old man had a history of head trauma 30 years ago. He was admitted to our department on October 16, 1989, because of an aneurysm incidentally found by a CT scan taken for the examination of his vertigo. Angiograms revealed a large aneurysm at the C3 portion of the right internal carotid artery. A right frontal craniotomy was performed on November 2, 1989, but neck clipping of the aneurysm was impossible, because it was a pseudoaneurysm with quite a fragile neck. Subsequently, fourteen occluding spring emboli were inserted into the aneurysm through a polyethylene catheter directly into the aneurysmal dome. Postoperative angiograms showed almost complete obliteration of the aneurysm with good preservation of the parent artery. Case 2: This 26 year-old woman without a history of head trauma was admitted to our department on May 10, 1989, complaining of right conjunctival injection and exophthalmos. Angiograms revealed a spontaneous CCF which had a single orifice at the C4 portion of the right internal carotid artery and drained through the superior ophthalmic vein and inferior petrosal sinus. Initially, transarterial and transvenous approaches were tried, but the attempts were unsuccessful. Subsequently, a right frontotemporal craniotomy was performed on August 8, 1989, and 27 occluding spring emboli were placed into the cavernous sinus through a polyethylene catheter which had been inserted directly.(ABSTRACT TRUNCATED AT 250 WORDS)