[A case of torsade de pointes in a patient with severe aortic stenosis during carotid endarterectomy].

An 87-year-old man with severe aortic stenosis developed torsade de pointes (TdP) during carotid endarterectomy before carotid artery stenosis. By prompt resuscitation and medication including lidocaine and magnesium, the patient recovered without complications in spite of high risk for refractory cardiac arrest or brain infarction. There was no other history or laboratory data suggesting arrhythmia except elongation on preoperative electrocardiogram. Inhaled anesthetics, catecholamine and sympathetic nerve stimulation were possible causes of QT elongation and induce TdP. Particularly in a patient with carotid and cardiac diseases, cardiac arrest is critical. Therefore we should avoid exacerbating factors of QT elongation or TdP even if patients have no particular history of arrhythmia.

Dynamics of global gene expression changes during brain metastasis formation.

As methods of cancer diagnosis and treatment improve, interest in metastatic brain tumors continues to increase. In the present study, we attempted to characterize genetically the dynamic changes occurring during brain metastasis formation by DNA microarray, and attempted to compare these findings with histological observations. Lewis lung carcinoma cells were injected into C57BL/6Ncrj mice carotid arteries. The mice were sacrificed at days 1-9 after injection. We performed histological observation and genome-wide expression profiling using a DNA microarray. In histological observation, tumor cells were observed in capillary vessels at day 1 after injection. At day 3, the tumor cells had begun to proliferate. At day 6, the metastatic foci showed "perivascular proliferations". Next, we performed a pairwise comparison of gene expression microarray data from day 1 to day 9 after injection. The first major change occurred between Phase Two and Phase Three. When hierarchical clustering was performed between different samples using the 867 genes, they could be classified into identical clusters for days 1 and 2, identical clusters for day 3 to day 5, and identical clusters for day 6 to day 9. For time course analysis, we extracted 623 genes by the pairwise comparison. By using the quality threshold (QT) nonhierarchical clustering method, we identified 37 expression patterns. These patterns can be separated into eight clusters by using the k-means method. The microarray results reported here strongly suggest that a large number of genes exhibit a spike pattern, which is tantamount to phase-specific expression.

An experimental model of brain metastasis of lung carcinoma.

Most metastatic brain tumors originate from lung cancers. However, there has been relatively little progress on developing an experimental model of metastasis of lung cancer to the brain. By injecting Lewis lung carcinoma cells into the right internal carotid artery of C57BL/6NCrj mice, we succeeded in developing a model of metastatic brain tumors. In this model, carcinoma cells proliferated in the choroid plexus of the right lateral ventricle and formed a nodular tumor mass, while carcinoma cells in the cerebral parenchyma multiplied along the perivascular sheath without forming a nodular mass. Twelve days after injection, carcinoma cells spread into the left hemicerebrum. Fifteen days after injection, carcinoma cells could be seen in both hemispheres, along with intraventricular tumor formation. The maximum life span of mice with metastatic brain tumors was 22 days. Our model essentially replicated the general process of metastatic cancer and may have a significant role in further research on brain metastasis of lung cancer.

Comparison of metastatic brain tumour models using three different methods: the morphological role of the pia mater.

As methods of cancer diagnosis and treatment progress, interest in metastatic brain tumours continues to increase. There are many studies using various methods of animal model and we considered that each model reflects different pathological processes because of the unique composition of the brain. We prepared metastatic brain tumour models using three different methods. In this study, we attempted to elucidate the roles of the pia mater in brain metastasis. The metastatic foci showed an angiocentric pattern, forming collars of neoplastic cells, and were designated 'perivascular proliferations'. Furthermore, we observed neoplastic cells that infiltrated the brain parenchyma, the border of which had become indistinct. These were labelled 'invasive proliferations'. The internal carotid artery injection model reflects haematogenous metastasis. In this model, both perivascular and invasive proliferations were observed. The intrathecal injection model reflects leptomeningeal carcinomatosis. In this model, metastasis to the meninges was observed. In the stereotactic injection model, the tumour proliferation at the injection site and the infiltration into the brain parenchyma were observed. The pia-glial membrane serves as a scaffold when neoplastic cells spread to the perivascular space forming angiocentric pattern. The pia-glial membrane is found between the brain parenchyma and blood vessels. Blood vessels penetrate the brain through tunnels known as perivascular spaces that are covered by pia mater. Three different methods which we prepared reflect three different pathological processes. Our findings suggest that the pia mater is a critical factor in brain metastasis.

A case of concomitant occurrence of struma ovarii and malignant transformation of cystic teratoma.

A 77-year-old woman received a total abdominal hysterectomy and bilateral salpingo-oophorectomy because of a tumor in the left ovary. The surgical specimen measured 8.5x4.5x4.0 cm, and the solid lesion measured 4.0x3.5x3.5 cm. The solid lesion was diagnosed as struma ovarii. The cyst wall partially comprised squamous epithelium-like and ciliated columnar epithelium-like cells. The tumorous lesion of the cyst wall revealed a poorly differentiated adenocarcinoma. Immunohistochemically, the tumor cells were positive for cytokeratin7, and were negative for cytokeratin20 and thyroid transcription factor-1. The authors diagnosed that struma ovarii and other parats coexisted as a poorly differentiated adenocarcinoma that had arisen from a mature ovarian cystic teratoma. As for the identification of the origin of adenocarcinomas arising from mature ovarian cystic teratomas, more cases need to be identified and investigated.

Disappearance of HCV after cessation of immunosuppression in a patient with ulcerative colitis and renal transplantation.

We report a patient, a 45-year-old Japanese woman, who underwent living-related donor renal transplantation in 1986 and 1988, with the second procedure being successful. Ulcerative colitis (UC) was diagnosed in 1987 while she was receiving immunosuppressive therapy after the renal transplantation. She became positive for serum anti-hepatitis C virus (HCV) in November 1990, although her serum aminotransferase levels were normal. In June 2001, she had frequent episodes of melena with abdominal pain, as control of her UC deteriorated. In July 2001, she was admitted to the Department of Surgery at our hospital, and her daily dose of prednisolone was increased from 40 mg to 80 mg. After 2 weeks of high-dose prednisolone therapy, there was a significant increase of serum aminotransferases, and serum HCV-RNA rose above 850 KIU/ml (by reverse transcription-polymerase chain reaction [RT-PCR]). Control of UC was still poor, so cyclosporine A (CyA) was added at a dose that maintained a high serum concentration. The daily dose of prednisolone was tapered and leukapheresis was performed three times weekly. As result, serum aminotransferases decreased to the normal range. However, total colectomy and colostomy were required because the UC could not be controlled by these therapies. Serum aminotransferase levels increased transiently 2 months after the cessation of immunosuppressive therapy (prednisolone, azathioprine [AZP], and CyA). Subsequently, serum aminotransferases rapidly declined below normal, and the serum level of HCV-RNA (by RT-PCR) fell from 480 KIU/ml to less than 0.5 KIU/ml. She was discharged on April 25, 2002. During follow-up as an outpatient, serum HCV-RNA became negative and remained negative for 7 months. To confirm clearance of HCV, liver biopsy was performed, and no HCV-RNA was detected in the liver tissue by RT-PCR. These findings suggested that HCV was cleared by the cessation of immunosuppressive therapy, as a rebound effect.

Granuloma and cryptococcosis.

This review describes the general histopathological features of cryptococcosis in immunocompetent individuals, as well as in patients with acquired immunodeficiency syndrome (AIDS). Details of the histological examination of cryptococcal lesions are described, with the consideration of morphological modifications induced by treatment with highly active antiretroviral therapy (HAART). The essential histological features of cryptococcosis in individuals with impaired T-cell functioning are yeast-cell proliferation with a histiocytic response, but only minor lymphocytic and neutrophilic components. Several histological patterns of pulmonary cryptococcal lesions are introduced in this article, some of which could be graded with respect to the degree and type of inflammatory reaction. One pattern was a mild lesion consisting of scattered small foci of intraalveolar cryptococcal proliferation with a histiocytic response. Another pattern involved massive cryptococcal infection, which may have been simply more extensive than that in the mild lesion. Capillary involvement of alveolar septa should be understood as an important common finding in patients with AIDS who had not been treated with HAART. In those patients, the absence of T cells and a decreasing function of antigen-presenting activity in histiocytes were confirmed by immunohistological examination. These findings suggest that the lungs of AIDS patients without HAART offer little resistance to bloodstream dissemination by cryptococci. The unique histological feature demonstrated in patients treated with HAART is characterized by the presence of CD4+ cells, greater response of histiocytes and multinucleated giant-cell formation, and lack of massive capillary involvement.

Cellular kinetics and K-ras codon 12 mutations according to histomorphometric type of colorectal polyps with epithelial serrated proliferation.

Recent studies have examined cellular kinetics and genetic abnormalities in colorectal polyps with epithelial serrated proliferation (CP-ESP), including hyperplastic polyps, serrated adenomas, and tubulovillous adenomas. However, difficulty in histologically classifying these lesions and the lack of clear-cut diagnostic criteria have led to inconsistent findings. Some 60 cases of CP-ESP and 6 cases of CP-ESP with malignant transformation were studied. When nuclear size progressively decreased from the bottom and middle layers to the surface layer of the crypts, maturation gradient was considered positive. CP-ESP and CP-ESP adjacent to carcinoma were morphologically classified as being positive or negative for maturation gradient and inferior and lateral glandular branching. Cellular kinetics were evaluated using Ki-67 immunostaining, and polymerase chain reaction (PCR)-dependent preferential homoduplex formation assay was performed to detect the presence or absence of K-ras codon 12-point mutations. CP-ESPs were morphologically classified into five types. In CP-ESP of types 1 to 4, the proliferation zone was confined to the bottom layer of the crypts or extended from the bottom to middle layers. In contrast, the proliferation zone extended throughout the crypts in most type 5 lesions. K-ras codon 12 mutations were detected in only types 3 and 5 CP-ESP. The five histomorphologic types of CP-ESP have distinct patterns of cellular kinetics. Histomorphologically, type 3 CP-ESP is considered an atypical hyperplastic polyp, occasionally associated with an elongated proliferation zone or K-ras mutations. Preliminary evidence indicates some relation between K-ras mutations and structural atypia associated with lateral branching of the crypts.

Duration of vecuronium-induced neuromuscular block can be predicted by change of skin temperature over the thenar muscles.

PURPOSE: The purpose of this study was to clarify the relationship between skin temperature over the thenar muscles and the duration of action of vecuronium measured acceleromyographically at the thumb in anesthetized patients. METHODS: In 15 patients undergoing elective open abdominal surgery under propofol, fentanyl, and nitrous oxide anesthesia, train-of-four (TOF) stimuli were delivered over the ulnar nerve at 2 Hz every 15 s, and the degree of neuromuscular block was measured acceleromyographically at the thumb. Each patient received an intubating dose of vecuronium 0.1 mg x kg(-1), followed by maintenance doses of 0.02 mg x kg(-1) administered repeatedly whenever the first twitch of TOF responses had recovered to 25% of control. The interval between maintenance doses was defined as the clinical duration (DUR25). The median values of skin temperature (ST) over the ipsilateral thenar muscles and esophageal temperature (ET) were recorded during the action of the first and all subsequent maintenance doses. The relationships between change in temperature and change in DUR25 were analyzed. RESULTS: Whereas ET showed only minor changes (median, -0.3 degrees C), ST fluctuated markedly between +0.9 degrees and -6.3 degrees C (median, -1.4 degrees C). Increase and decrease were also seen in a series of DUR25s, as expected from the changes in ST. The median values of DUR25 produced by the first and last maintenance vecuronium doses were 21.5 and 32.3 min, respectively. A negative linear correlation was found between the change in DUR25 and that in ST, demonstrating that DUR25 increased by 20% of baseline with each 1 degrees C decrease in ST. CONCLUSION: Our results show that peripheral ST decreases considerably during open abdominal surgery without reduction in core temperature, and the decrease contributes to the potentiation of neuromuscular block in the periphery during propofol, fentanyl, and nitrous oxide anesthesia.

Pathophysiology of pulmonary aspergillosis.

A description of the pathophysiology of aspergillosis is followed by a review of investigational considerations of animal models. Because a large body of invasive Aspergillus infection occurs as opportunistic infection, there is a large spectrum of the histopathological feature of lesions demonstrated at the site of infection. Histopathology of the lesions can be understood as a phenotypical representation of interaction between lowered defense mechanisms in the host and the virulence of invading fungi. Detailed observations with a consideration of previous pathological knowledge of infection and inflammation provide much important information useful in predicting the pathophysiology of the patient. Moreover, experimental studies can also provide much insight to elucidate pathogenesis of the infection that emerges from the clinical and pathological investigations. The importance of pathophysiology should be emphasized to understand the implications of radiographic images, clinical symptoms, and laboratory dates. By reviewing these, especially computed tomography (CT) images, we can see that they accurately mirror the histological features of the lesion that can be recognized as a phenotypical representation of pathophysiology of Aspergillus infection. This is also confirmed by the reports emphasizing the importance of CT scans to identify hallmark clinical signs and symptoms of the disease.

[A retrospective study in spinal anesthesia for sumo-wrestlers].

BACKGROUND: Spinal anesthesia for the Sumo-wrestler is thought to be difficult because of following reasons. 1. Sumo-wrestlers are so fatty and weighty that piercing spinal needle into the subarachnoid space is technically difficult. 2. The relationship between volume of local anesthetics and attained spinal anesthesia level is difficult to detect. 3. Upper airway can be easily obstructed during sedation. METHODS: Retrospectively, we compared 30 Sumo-wrestler patients (group S) with normal body weight patients (group N) concerning 17 items. RESULTS: While all patients in group N were approached from L 3 and L 4 interspinal space using 25 gauge spinal needles, 13 patients in group S were approached from another interspinal space, for example L 2 and L 3 or L 4 and L 5 and 40% of patients in group S needed 23 gauge spinal needles. The time intervals from the entrance into the operating room till the end of intrathecal administration of local anesthetics in group S and group N were 34 and 24 minutes, respectively (P < 0.05). The distances from the surface of the skin to subarachnoid space in group S and group N were 80 mm and 49 mm, respectively (P < 0.05). CONCLUSIONS: These results indicate that subarachnoid puncture in Sumo-wrestler patients is difficult and we should understand the specificities of spinal anesthesia for these patients.

Microvasculature of the human cerebral white matter: arteries of the deep white matter.

The vascular architecture of the human cerebral deep white matter was studied using soft X-ray and diaphanized specimens, achieved by intra-arterial injection of barium and vascular stain respectively, and also by electron microscopic examination of the corrosion cast of arteries in normal adult brains. The deep white matter arteries passed through the cerebral cortex with a few branches to the cortex and ran straight through the white matter. The arteries concentrated ventriculopetally to the white matter around the lateral ventricle. Anastomoses were noted around the ventricular wall at the terminals of the deep white matter arteries. No centrifugal branches irrigating the periventricular white matter from the lenticulo-striate arteries were observed in the present study. The presence of anastomoses among the terminal branches of deep white matter arteries protects against ischemic change or infarction in this area from an occlusion of a single deep white matter artery. This may lead to development of terminal zone infarction from ischemia or vascular diseases, affecting multiple deep white matter arteries. The subcortical and deep white matter arteries had thick adventitial sheaths and large adventitial spaces in the white matter but not in the cortex. The presence or absence of the adventitial space is regarded as another characteristic difference between the arteries in the white matter and cortex. This difference may influence pathological changes in vascular lesions in these respective areas.

Microvasculature of the human cerebral meninges.

In the present study, the human cerebral meninges were rich in blood vessels, but no capillaries were noted. The meningeal arteries ran over the veins where they crossed. Several arterial anastomoses existed on the cortical surface. The meningeal arteries were classified into four parts; the conducting artery approximately 700 microm in diameter, distributing artery approximately 200 microm in diameter, precortical artery approximately 60 microm in diameter and cortical artery approximately 30-40 microm in diameter. A single distributing artery supplied the area of approximately 3.5 x 2.0 mm on the brain surface. They further ramified into precortical arteries which stemmed cortical arteries. These precortical arteries had the distributing area of 1 mm2 and this distributing area was the same size as the width of human ocular dominant column of the visual cortex. Constriction, like a sphincter, was observed at the bifurcation of the distributing arteries. The cerebral blood vessels, which regulated the blood flow and reacted to autonomic nerve stimuli, seemed to correspond to the distributing arteries.

Clinical and pathological differences between alcoholic hepatitis and non-alcoholic steatohepatitis.

To determine the difference between alcoholic hepatitis (AH) and non-alcoholic steatohepatitis (NASH) in Japan, six patients with Ah and four patients with NASH, recently treated at our institute, were clinically and pathologically evaluated. Clinical features of the diseases differed: in NASH patients, mean age was higher, mean body mass index much higher, and the prevalence of diabetes mellitus was higher than in AH patients. The patients with NASH presented with unremarkable symptoms and signs. Abnormalities in liver function tests including prothrombin time and choline esterase were mild in NASH patients, except for the indocyanine green test. They had ALT-dominant hypertransaminasemia. AST, ALT and gamma GTP did not normalize as promptly as in AH patients after admission. However, there was no significant difference in the histological grade of fibrosis, inflammation or hepatocytic metamorphosis between NASH and AH patients. Stellate-form fibrosis was characteristic of AH, whereas pericellular and perivenular types were common in NASH patients. Focal cell necrosis was rather intense, and fatty deposits prominent, in NASH patients. However, it was difficult to histopathologically discriminate between NASH and AH patients. If AH is histologically suspected in non-alcoholic patients, the possibility of NASH should always be considered. Furthermore, even in patients with suspected simple fatty liver, a liver biopsy should be performed, especially in cases with prolonged abnormal liver function findings.

The microvasculature of the cerebral white matter: arteries of the subcortical white matter.

The microvascular architecture of the human cerebral subcortical white matter was studied. Most of the subcortical arteries ran straight through the cortex, but upon entering the white matter, they began to coil, loop, and spiral. Vascular stains showed wide spaces between the adventitial sheaths and blood vessels. The blood vessels coiled, looped, and spiraled within these wide adventitial spaces. This phenomenon was observed in the brains from persons ranging from the first to ninth decades of life and there were no statistically significant age-related correlations. Furthermore, there was no evidence of a reduction in the volume of white matter after fixation. Therefore, the observed tortuosity does not appear to be the result of shrinkage of brain tissue following fixation. While the mechanisms responsible for the subcortical arteries circuitry remain undetermined, this coiling architecture may serve as a trap for tumor cells and microorganisms passing through the blood stream, suggesting that these coiling arterial blood vessels may play a significant role in the pathogenesis of tumor metastasis and the brain abscess that frequently occurs in the gray-white matter junction.

The microvasculature of the human cerebellar meninges.

The vascular architecture of the human cerebellar meninges was investigated. The surface meninges were poor in vasculature. In the sulci, the meninges were highly vascular but had few capillaries. The venous blood vessels gave long side branches at right angles to the parent vessels in a cruciform pattern, running horizontally along the cerebellar sulci. They were situated at the origin of the secondary or tertiary sulci. Anastomoses between these horizontal branches gave a crosshatched appearance. Short branches often extended to the bases of the sulci, terminating in T-shaped bifurcations with numerous tiny branches, like the roots of a tree. The arteries ran perpendicular to venous branches which were parallel to each other exclusively along the sagittal plane. These arteries bifurcated to straddle the horizontally running veins at the origin of the secondary or tertiary sulci. They gave off many small branches like teeth of a fork from each artery in the secondary or tertiary sulci after they bifurcated to straddle the venous branches and penetrated the cerebellar cortex at the bases of sulci. These fork-like ramifications in the bases of the sulci were most likely responsible for the ready development of pronounced ischemic state. They might also play an important role in the occurrence of ischemic damage at the bases of sulci in cases of severe generalized ischemia.