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Pedersen PM, Jorgensen HS, Kammersgaard LP, Nakayama H, Raaschou HO, Olsen TS: Manual and oral apraxia in acute stroke, frequency and influence on functional outcome: the Copenhagen Stroke Study. Am J Phys Med Rehabil 2001;80:685‐ 692. Objectives: To determine the frequency of manual and oral apraxia in acute stroke and to examine the influence of these symptoms on functional outcome. Design: Seven hundred seventy six unselected, acute stroke patients who were admitted within seven days of stroke onset with unimpaired consciousness were included. If possible, the patients were assessed for manual and oral apraxia on acute admission. Neurologic stroke severity including aphasia was assessed with the Scandinavian Stroke Scale, and activities of daily living function was assessed with the Barthel Index. All patients completed their rehabilitation in the same large stroke unit. Results: Six hundred eighteen patients could cooperate with the apraxia assessments. Manual apraxia was found in 7% of subjects (10% in left and 4% in right hemispheric stroke; 2 9.0; P 0.003). Oral apraxia was found in 6% (9% in left and 4% in right hemispheric stroke; 2 5.4; P 0.02). Both manual and oral apraxia were related to increasing stroke severity, and manual, but not oral, apraxia was associated with increasing age. There was no gender difference in frequency of apraxia. Patients with either type of apraxia had temporal lobe involvement more often than patients without. When analyzed with multiple linear and logistic regression analyses, neither manual nor oral apraxia had any independent influence on functional outcome. Conclusion: Apraxia is significantly less frequent in unselected patients with acute stroke than has previously been assumed and has no independent negative influence on functional outcome.

In the Copenhagen Stroke Study, we evaluated the combined impact on stroke outcome of potentially treatable factors such as acute body temperature, blood glucose, and stroke in progression. The patients were stratified into two groups: (1) patients with ‘good’ prognostic parameters (body temperature on admission ≤37.0°C and plasma glucose on admission ≤6.5 mmol/l and who did not develop stroke in progression) and (2) patients with correspondingly ‘poor’ prognostic parameters. A poor outcome was observed in 4% of the patients with good prognostic parameters versus in 49% of the patients with poor prognostic parameters (p < 0.01). In the multivariate analysis which also included stroke severity, blood glucose contributed significantly to poor outcome with an odds ratio (OR) of 1.2/1.0 mmol/l increase, body temperature with an OR of 2.2/1°C increase, and stroke in progression with an OR of 2.9. However, the combined effect of all three factors was more than additive with an OR of 10.0 (95% CI 1.5–56; p < 0.01). We have shown that in human stroke a strong and more than additive association exists between potentially reversible parameters and outcome. Intervention trials can prove whether these marked relations are causal.

Uridine diphosphate (UDP)-GalNAc: polypeptide N-acetylgalactosaminyltransferase (GalNAc transferase) catalyzes the initial step in mucin type O-glycosylation, and its expression has been assumed to be altered between normal epithelial cells and cancer cells. We studied the alteration of GalNAc transferase expression during the carcinogenesis of human colorectal epithelial cells. We produced polyclonal antibodies against synthetic polypeptides with specific sequence to two GalNAc transferase isozymes, T1 and T2. Surgically resected specimens from 50 patients with colorectal cancer were immunohistochemically stained, and the staining grade (percentage of positively stained cells) was compared between cancer and its normal counterpart in the same specimen. Significant signals for both T1 and T2 expression were seen in the supranuclear region of normal and cancer cells, indicating the subcellular localization of the enzymes in the Golgi apparatus. The prevalence of positive staining for T1 and T2 expression in colorectal cancer was significantly higher than that in normal epithelium (P < 0.05). However, the difference in staining grades between cancer and normal tissues varied in each patient. These results indicate that there is variability in the expression patterns of GalNAc transferase isozymes in normal and cancerous cells colorectal among individuals.

Background and Purpose —The beneficial effects of treatment and rehabilitation of patients with acute stroke in a dedicated stroke unit (SU) are well established. We wanted to examine if these effects are limited to certain groups of patients or if they apply to all patients independent of age, sex, comorbidity, and initial stroke severity. Methods —This was a community-based study of outcome in 1241 consecutive stroke patients from 2 communities in Copenhagen: In one (Frederiksberg), treatment and rehabilitation were given in general neurological and medical wards (GW), and in the other (Bispebjerg) in one single large SU. Outcome measures were initial, 1-year, and 5-year mortality rates, a poor outcome (initial death or discharge to a nursing home), and length of hospital stay (LOHS). Multivariate regression analyses were used to examine the independent effect of SU treatment on the various subgroups. Results —The relative risks of initial death, poor outcome, and 1-year and 5-year mortality rates were reduced by 40% on average in patients treated in the SU compared with the GW. A beneficial effect of SU treatment was observed regardless of the patient’s age, sex, comorbidity, and initial stroke severity. Those who benefited most appeared to be the patients with the most severe strokes (poor outcome: OR 0.17; 95% CI 0.05 to 0.58). Those who benefited least were patients with mild or moderate strokes (poor outcome: OR 0.66; 95% CI 0.41 to 0.98) and patients Conclusions —A beneficial effect of treatment in a SU is achieved in completely unselected patients independent of their age, sex, comorbidity, and stroke severity. Those who had the most severe strokes appeared to benefit most. All patients with acute stroke should therefore have access to treatment and rehabilitation in a dedicated SU.

Knowledge of neurological and functional outcome is essential when dealing with the treatment and rehabilitation of patients with stroke. This article describes functional and neurological outcome and speed of recovery in relation to initial stroke severity. Recovery of specific functions such as walking, upper extremity function, bowel and bladder, and language is also described. Detailed information about factors important to recovery including body temperature, blood glucose, stroke in progression, stroke type, and treatment on a dedicated stroke unit is given. The article is based on information from the 1,197 patients with acute stroke included in the community-based Copenhagen Stroke Study. All these patients had all their treatment and rehabilitation on a dedicated stroke unit regardless of their age, stroke severity, and premorbid condition.

This article examines the findings regarding the neurologic and functional recovery of patients from the Copenhagen Stroke Study. This article presents initial neurologic impairment and disability pattern and speed of recovery, final impairment and disability after completed rehabilitation, and prognostic factors in these stroke patients.

This article describes basic characteristics and primary outcomes of unselected patients with stroke. These patients were part of the Copenhagen Stroke Study, a prospective, consecutive, and community-based study of 1197 acute stroke patients. The setting and care was multidisciplinary and all treatment was performed within the dedicated stroke unit. Neurologic impairment was measured at admission, weekly throughout the hospital stay, and again at the 6-month follow up. Basic activities of daily living, as measured by the Barthel Index, were assessed within the first week of admission, weekly throughout the hospital stay, and again after 6 months. Upon completion of the in-hospital rehabilitation, which averaged 37 days, two-thirds of surviving patients were discharged to their homes, with another 15% being discharged to a nursing home. Only 4% of the patients with very severe strokes reached independent function, as compared with 13% of patients with severe stroke, 37% of patients with moderate stroke, and 68% of patients with mild stroke.

CD34 is a marker of haematopoietic progenitor cells, stromal precursors, vascular endothelial cells, and a variety of stromal tumour cells. This immunohistochemical study examined the CD34 expression of glomerular mesangial cells in normal and diseased glomeruli and compared it with the staining patterns of alpha-smooth muscle actin (ASMA), as a transformed mesangial cell marker, and CD31, as an endothelial cell marker. In addition, the CD34 and ASMA expression of mesangial cells in various glomerulonephritis and the relationship of the immunostaining intensity to the severity of IgA nephropathy were semiquantitatively evaluated. In normal glomeruli, all cell types were negative for CD34, but in glomeruli in mesangial proliferative glomerulonephritis, CD34 was expressed exclusively in mesangial cells, corresponding to ASMA expression. The dendritic and scattered staining pattern, the mesangial location of positive signals, and the enhanced expression were clearly different from CD31 expression in diseased glomeruli. In comparison with normal controls, the grade of immunostaining for CD34 (CD34 INDEX) in mesangial proliferative glomerular diseases was higher than that of ASMA (ASMA INDEX). With the severity of glomerulonephritis, the CD34 INDEX gradually increased. These studies indicate that CD34 is a useful marker of mesangial transformation and that immunohistochemical examination with the anti-CD34 antibody is useful for the diagnosis and stage determination of glomerular diseases.

Leukocytosis is a common finding in the acute phase of stroke. A detrimental effect of leukocytosis on stroke outcome has been suggested, and trials aiming at reducing the leukocyte response in acute stroke are currently being conducted. However, the influence of leukocytosis on stroke outcome has not been clarified. Methods: In 763 unselected patients with stroke admitted within 24 hours from onset, we prospectively studied the relation between leukocyte count and outcome considering relevant confounders and predictors such as initial stroke severity, risk factor profile, body temperature, and infection. Results: Univariate, leukocyte count on admission was significantly related to initial stroke severity (assessed by the Scandinavian Stroke Scale), lesion size on computed tomography, mortality, and outcome in survivors. However, multivariate regression analysis revealed that only the relation between leukocytosis and initial stroke severity was independent of other factors, whereas the relations found univariately between leukocytosis and lesion size, mortality, and outcome in survivors disappeared when initial stroke severity was included in the multivariate model. Conclusion: Leukocytosis on admission was related to initial stroke severity but not to outcome. Leukocyte count on admission seems merely to reflect initial stroke severity and is most likely a stress response with no independent influence on outcome. Our study may suggest that attempts aimed merely at lowering leukocyte count in peripheral circulating blood in the acute phase of stroke cannot be expected to improve outcome.

Collagenofibrotic glomerulonephropathy is a new disease entity of unknown pathogenesis, which is characterized by the deposition of type III collagen within the mesangial matrix. We have investigated a case in which many mesangial cells in the type III collagen-deposited glomeruli were α-smooth muscle actin (ASMA) positive and showed an increase of subplasmalemmal filaments, indicating the activation and myofibroblastic transformation. It is suggested that the activated mesangial cells may synthesize the type III collagen deposited in the subendothelial space and mesangial matrix.

We report a case of a 17-year-old man with a spindle cell tumor in the occipital subcutaneous tissue. The enucleated tumor, measuring 2.5 x 2.0 x 1.0 cm, had a broad-bean shape and well circumscribed border and was localized to the subcutis without dermal involvement. Microscopically, the tumor was composed of uniform spindle cells showing interlacing bundle formation and a herringbone pattern. The neoplastic cells were separated by collagen fibers in parallel fashion, the amount of which varied with different areas in the tumor. Mitotic figures were eight mitoses per 50 high-power fields in number. The neoplastic cells were positive for vimentin, Factor-XIIIa, alpha-smooth muscle actin and CD34, but negative for desmin, calponin, high molecular weight caldesmon, smooth muscle myosin heavy chain, collagen type IV, laminin and S-100 protein. These immunohistochemical results indicated that the neoplastic cells showed differentiation toward fibroblasts/myofibroblasts/dendritic interstitial cells. Although more than 50% of the neoplastic cells were positive for CD34, the present tumor should be diagnosed as well differentiated fibrosarcoma, adult type, rather than extrapleural solitary fibrous tumor and fibrosarcomatous areas of dermatofibrosarcoma protuberans, on the basis of routine microscopic findings mentioned above.

A recent study suggests that a high plasma level of tissue plasminogen activator (t-PA antigen) is a risk factor for stroke in men. Whether t-PA antigen is a risk factor for stroke in women is unknown. We measured plasma levels of t-PA antigen in 302 nonselected patients with acute ischemic stroke and in 138 healthy control subjects. In a subgroup of the patients, plasma t-PA antigen was remeasured 6 months after the stroke. Women with acute ischemic stroke (n=171) had median plasma t-PA antigen that was 39% higher than the healthy female control subjects (n=86): 10.3 (8.0 to 13.7) versus 7.4 (6.1 to 9.1) ng/mL (median [interquartile range]), P =.0001. At the reexamination of the patients after 6 months, plasma t-PA antigen was unchanged in the female patients. This suggests that the difference in plasma t-PA antigen between the female patients and the healthy control subjects did not result from an acute phase reaction. In a multivariate regression analysis, high t-PA antigen was an independent risk factor for stroke, and high plasma level of t-PA antigen was associated with severe stroke in women. The current data suggest that plasma t-PA antigen is elevated in women with ischemic stroke.

An immunohistochemical study of nine cases of chondroid syringomas/mixed tumors of the skin was performed to elucidate the nature of the so-called neoplastic myoepithelial cells (NMEC) in tumor tissues. These nine tumors contained NMEC of considerable variability in number from one tumor to another. These NMEC were classified into three types: (i) hyaline cells (plasmacytoid cells); (ii) spindle NMEC; and (iii) polyhedral cells. They showed different immunostaining patterns, as the following describes. Cytokeratin 14 was positive in most of the spindle NMEC and a large number of the polyhedral cells, and in a small number of the hyaline cells. Concerning low molecular weight cytokeratins, most of the hyaline cells showed immunoreactivity, whereas they were negative in many of the spindle NMEC and were expressed only in a small number of the polyhedral cells. alpha-Smooth muscle actin and muscle-specific actin were positive in the spindle NMEC but negative in any of the hyaline cells and polyhedral cells. These findings strongly indicate that the hyaline cells and the spindle NMEC are of the simple epithelial and myoepithelial types, respectively. The findings also suggest that the polyhedral cells show differentiation toward basal cells of the sweat gland dermal ducts or myoepithelial cells.

To investigate the pathogenesis of congenital hydrocephalus the brains of HTX rats aged between 16 days and 4 weeks and the brains of normal Wistar rats of the same ages were examined. In the fetal HTX rat brains, the lateral ventricles were symmetrically dilated from 20 days of gestation. The neuroepithelium bordering the ventricles showed thinning with cellular disarrangement and deformity. Similar neuroepithelial abnormalities were also found in the lateral ventricles of the HTX rat brain with no macroscopic signs of hydrocephalus at 20 days of gestation. The neuroepithelium showed flattening of the cells, widening of the intercellular spaces, formation of microvilli on the detached lateral cell surfaces, and frequent macrophage infiltration. On the other hand, the neuroepithelial cells of the third ventricle and the aqueduct were affected less severely or showed no significant abnormalities. Immunohistochemically, most of the neuroepithelium and ependyma of the lateral ventricles were positive for vimentin in both prenatal and postnatal hydrocephalic HTX rats, while a small number or none of those in normal control rats were positive. These morphological changes suggested that preferential involvement of the lateral ventricular neuroepithelium might be closely associated with the pathogenesis of congenital hydrocephalus in HTX rats.

肺の大細胞神経内分泌癌の1剖検例を経験したので報告する. 症例は62歳, 男性. 労作時呼吸困難, 胸部痛を主訴に近医受診. 右上肺野に異常陰影を指摘され, 当院紹介となり, 気管支鏡下擦過細胞診が施行された. 壊死を背景に多数の腫瘍細胞が認められ, 孤立散在性のものが多いが, 胞巣状, ロゼット状, インディアンファイル状に配列する像もみられた. 核は卵円形で, 中等大～大型であった. クロマチンは繊細あるいは粗顆粒状で増加しており, 核小体の目立つ細胞も認められた. 大型の腫瘍細胞が混在しているものの小細胞癌 (中間細胞型) が疑われた. 以後, 化学療法を受けたが, 肺炎を合併し, 亡くなり, 病理解剖が施行された. 組織学的に腫瘍はTravisらの提唱する肺の大細胞神経内分泌癌の典型像を呈していた. 本疾患の鑑別診断には小細胞癌や低分化扁平上皮癌, 腺癌, 大細胞癌などが考えられるが, 細胞の詳細な観察に加え, 積極的に特殊染色や免疫組織染色を行い, 総合的に判定することが重要と考えられる.

Background Cytologic descriptions of invasive lobular carcinoma of the breast with osteoclastlike giant cells (OGCs) are exceedingly rare. Clinically, breast carcinoma with OGCs can be confused with fibroadenoma. The histogenesis of OGCs has been the subject of debate. Case A 48-year-old female presented with a 1.5-cm, well-demarcated, firm, non-tender, mass involving the right breast. Fine needle aspiration biopsy (FNAB) showed the characteristic combination of relatively small, uniform carcinoma cells containing conspicuous intracytoplasmic lumina and numerous reactive multinucleated giant cells. OGCs were reactive for KP-1 and not stained with MIB-1. Conclusion The cytologic appearance of invasive lobular carcinoma with OGCs is characteristic. FNAB permits diagnosis of this rare type of breast carcinoma. Our study supported a histiocytic nature of the OGCs. OGCs were considered not actively proliferated cells.

A 69-year-old woman was admitted for further examinations and treatment of chest pain. Emergency cardiac catheterization showed no significant stenosis on coronary angiograms; however, diffuse wall hypokinesis was observed on a left ventriculogram. After treating the patient's heart failure, cardiac catheterization was performed again. A spasm provocation test showed coronary spasms of the right and left coronary arteries. A right ventricular endomyocardial biopsy revealed denaturation and fibrosis of the myocardium under the endocardium, thus suggesting the presence of myocardial ischemia. This case highlights coronary spasms as a cause of heart failure.

Background and Purpose: School-based interventions of stroke enlightenment are not only beneficial for students but also expected to deliver stroke message effectively to their parents. We produced stroke teaching materials using FAST mnemonic. The aim of this study is to verify the effectiveness of stroke education project (the Tochigi project) for delivering stroke message to their parents through their children, using our teaching materials of stroke enlightenment. Methods: Subjects were guardians of 1,125 students (13-15 y.o.) in 9 public junior high schools in Tochigi prefecture, Japan. All students received a 20-minute stroke lesson by their teacher using the FAST mnemonic, and then watched a 10-minute animated cartoon and read the comic book. At the close of the lesson, the teacher asked the students to take back the comic book and talk about stroke with their guardians while showing the comic book. Questionnaires on stroke knowledge were examined for all the guardians before and immediately after the conversation about stroke with their children. Results: There were 915 guardians (81.3%, 94%; parents) participated in the present study. Correct answer rates for the questions of headache (81.1 vs. 72.8%, p Conclusions: Our teaching materials of stroke enlightenment for junior high school students would be promising means of delivering the stroke message effectively to their guardians.

We report one rare case of superficial angiomyxoma of the right inguinal region, in a 67-year-old man. The tumor, measuring 4.5 x 4.0 x 3.0 cm, had a finger-like shape, was composed of a well circumscribed conglomerate of multiple myxomatous nodules and was located partially in the dermis and partially in the subcutaneous tissue. Microscopically, in contrast to previously reported cases, the tumor was composed mainly of oval plump stromal cells with an amphophilic cytoplasm. Spindle-shaped stromal cells were scattered throughout the tumor. The tumor border was not infiltrative and was well defined by thick hyalized collagen bundles. Neither hyperchromasia nor pleomorphism was apparent. No mitotic figures were detected in the specimens prepared. Small to medium-sized blood vessels showed a scattered distribution, but large vessels, seen frequently in aggressive angiomyxoma, were absent. Moreover, no plexiform capillary pattern was evident. These findings were diagnostic of superficial angiomyxoma. Although this disease entity is considered as including cutaneous focal mucinosis, follicular fibroma, trichofolliculoma and trichogenic adnexal tumor, we propose that these tumors should be excluded.

Widely different incidences have been found for hemineglect in acute stroke, and there is no agreement on the consequences of hemineglect for activities of daily living recovery. We assessed acute admission visuo-spatial and personal hemineglect in a prospective, community-based study of 602 consecutive stroke patients. Hemineglect was found in 23%. Functional outcome was assessed with the Barthel Index (BE), length of rehabilitation, mortality, and rate of discharge to independent living. The independent influence of hemineglect on outcome was analyzed with multiple linear and logistic regression analysis also including functional and neurologic scores on admission, age, gender, previous stroke, comorbidity, anosognosia, orientation, and aphasia. Marital status was also included in the analysis of determinants of discharge to independent living. Hemineglect had no independent influence on admission BI, discharge BI, length of hospital stay used for rehabilitation, mortality, or rate of discharge to independent living. It is concluded that hemineglect per se has no negative prognostic influence on functional outcome.

Uterine adenomatoid tumors (UATs) are benign tumors of the uterine serosa and myometrium that originate from the mesothelium and forming gland-like structures. This study was conducted in order to determine the true incidence of UATs, which are usually an incidental finding during uterine surgery performed for other causes. UATs may resemble pre-existing vessels and lymphatic ducts, as well as metastatic adenocarcinomas. A total of 199 consecutive surgical operations (134 hysterectomies and 65 uterus-preserving tumor excisions) were performed by a single team of gynecologists and examined by a single attending pathologist, who performed a thorough macro- and microscopic examination of all the specimens. UATs were identified in nine (5%) out of the 199 cases [six (5%) out of the 134 hysterectomies and three (5%) out of the 65 uterus-preserving tumor excisions]. Therefore, the true incidence of UATs may be significantly higher than 1%, which is the incidence reported in the presently available literature.

Background Atrial fibrillation (AF) is a common arrhythmia and a major risk factor for stroke. Many physicians remain reluctant to provide stroke prevention by anticoagulant therapy especially for elderly individuals with AF. Using multivariate regression analyses, we studied the characteristics and the prognosis of stroke in patients with AF. Methods The study is part of the Copenhagen Stroke Study, a prospective, community-based study of 1197 patients with acute stroke treated on a stroke unit from the time of acute admission to the end of rehabilitation. Initial stroke severity was measured by the Scandinavian Neurological Stroke Scale (SSS). Neurological and functional outcomes were evaluated by the SSS and the Barthel Index. Results AF was diagnosed in 18% of the patients. AF increased steeply with age in the stroke population, from 2% in patients P Conclusions Stroke in patients with AF is generally more severe and outcome markedly poorer than in patients with sinus rhythm. This accentuates the importance of anticoagulant treatment of individuals with AF. A lower blood pressure in the acute stage of stroke may contribute to the increased stroke severity in patients with AF.

Medical treatment of stroke is dependent on a narrow therapeutic time window.We prospectively analyzed the influence of demographic, medical, and pathophysiologic factors on admission delay in 1,197 unselected, acute stroke patients. Twenty five percent were admitted within 3 1/2 hours, 35% within 6 hours, 50% within 14 hours, and 68% within 24 hours after stroke onset. Living alone (odds ratio [OR] 1.75, 95% CI 1.3 to 2.3) and retired working status (OR 1.61, 95% CI 1.01 to 2.54) delayed admission. A well-working social network thus seems important to early admission. The milder the stroke, the higher was the risk of delayed admission (OR 1.25 per 10 points decrease in stroke severity [Scandinavian Neurological Stroke Scale score on admission], 95% CI 1.14 to 1.36). A history of TIA increased the relative chance of early admission by odds 1.64 (95% CI 1.06 to 2.54). Other factors such as age, sex, diabetes, hypertension, ischemic heart disease, other comorbidity, previous stroke, headache, aphasia, apraxia, anosognosia, neglect, lowered consciousness, mental status (Mini-Mental State Examination) and type of stroke (hemorrhage/infarct) had no independent influence on admission time. Admission was markedly delayed in most patients. This represents a major barrier to medical treatment. Patients with the most severe strokes are admitted early, but patients with milder symptoms should also be encouraged to seek immediate admission. The observation that a history of TIA reduced admission time indicates that an increase in public awareness and knowledge may reduce delay and save precious time.NEUROLOGY 1996;47: 383-387

We report a case of ancient schwannoma, which is a rare benign neoplasm of the oral floor and ventricular portion of the tongue. Only two cases have previously been reported in the English literature. The present tumor, measuring 5.5 x 3.0 x 3.0 cm, was the largest of the three. To differentiate ancient schwannoma from schwannoma with malignant transformation, it is important to confirm the absence of abrupt transition between areas of apparently typical schwannoma and areas composed of atypical large cells with pleomorphic and hyperchromatic nuclei, as well as the absence of mitoses, necrosis, and invasiveness. In the present case, calcification was not detected, nor was hyalinization extensive, although many of the neoplastic Schwann cells showed degenerative nuclear atypia.

Abstract Serum levels of total and free testosterone and 17β-estradiol were determined in 144 men with acute ischemic stroke and 47 healthy male control subjects. Blood samples from patients were drawn a mean of 3 days after stroke onset and also 6 months after admission in a subgroup of 45 patients. Initial stroke severity was assessed on the Scandinavian Stroke Scale and infarct size by computed tomographic scan. Mean total serum testosterone was 13.8±0.5 nmol/L in stroke patients and 16.5±0.7 nmol/L in control subjects ( P =.002); the respective values for free serum testosterone were 40.8±1.3 and 51.0±2.2 pmol/L ( P =.0001). Both total and free testosterone were significantly inversely associated with stroke severity and 6-month mortality, and total testosterone was significantly inversely associated with infarct size. The differences in total and free testosterone levels between patients and control subjects could not be explained by 10 putative risk factors for stroke, including age, blood pressure, diabetes, ischemic heart disease, smoking, and atrial fibrillation. Total and free testosterone levels tended to normalize 6 months after the stroke. There was no difference between patients and control subjects in serum 17β-estradiol levels. These results support the idea that testosterone affects the pathogenesis of ischemic stroke in men.

To determine the influence of initially lowered orientation on rehabilitation outcome in stroke patients, and how decreased orientation 6 months after stroke influences ADL and social activities.Prospective, consecutive, and community based.A stroke unit receiving all acute stroke patients from a well-defined catchment area. All stages of rehabilitation were completed within the unit.524 patients with acute stroke.Basic ADL assessed by the Barthel Index (BI) at discharge; discharge placement; higher level ADL and social functions assessed by the Frenchay Activity Index(FAI) at a 6-month follow-up.The independent influence of orientation in acute stroke on rehabilitation outcome was analyzed with multiple linear and logistic regression models, using initial stroke severity (Scandinavian Neurologic Stroke Scale), initial BI, age, sex, comorbidity, prior stroke, and marital status as covariates. A one-point decrease in orientation decreased BI with 9 points (coefficient b=8.66, SE(b)=1.02,p.0001) and reduced the likelihood (1.49, 95% CI: 1.05 to 2.11) of discharge to independent living (b=.40, SE(b)=.18,p=.026). Follow-up examinations 6 month poststroke showed that decreased orientation at this point still exerted a marked, negative influence on ADL and social functions (BI: coefficient b=12.06, SE(b)=1.95,p.0001; FAI: coefficient b=6.28, SE(b)=1.42,p.0001).The level of orientation influences basic ADL and higher level ADL and social activities in acute as well as chronic stroke. This finding suggests that rehabilitation of memory and attention might be relevant in stroke patients with impaired orientation.

Anosognosia is a well-known symptom after stroke but its frequency following acute stroke is not known and knowledge of its impact on functional outcome is limited. This prospective study included 566 consecutive, unselected, acute stroke patients. Anoso gnosia was evaluated on acute admission using the test of Bisiach et al. (1986), stroke severity with the Scandinavian Neurological Stroke Scale (SNSS), and activities of daily living (ADLs) with the Barthel Index (BI). Multiple linear and logistic regres sion analyses were done to find the influence of anosognosia on the outcome of stroke per se. The frequency of anosognosia was 21% on acute admission. The lesion was located in the right hemisphere in 81% of the patients. Anosognosia was seen more frequently following cortical vs. subcortical lesions but showed no significant rela tionship to any of the four cortical lobes. The presence of anosognosia per se predicted 11.5 points less in discharge BI, increased the likelihood of death during the hospital...

Objectives: A "pusher syndrome" encompassing postural imbalance and hemineglect is believed to aggravate the prognosis of stroke patients. Our aim was to determine the incidence, associated neuropsychological symptoms, and the consequences for rehabilitation of ipsilateral pushing. Design: Consecutive and community-based. Setting: A stroke unit receiving all acute stroke patients from a well-defined catchment area. All stages of rehabilitation were completed within the unit. Patients: 647 acute stroke patients admitted during a 1-year period. Excluded were 320 patients who did not receive physiotherapy because they did not have pareses of the leg, had a fast remission, or died. Main Outcome Measures: Gain in activities of daily living (ADL) function (Barthel Index), time course of functional remission, and discharge rate to nursing home. The independent impact of ipsilateral pushing was analyzed with multiple linear and logistic regression analyses. Results: Ipsilateral pushing was found in 10% of the included patients. No significant differences were found in the incidence of hemineglect and anosognosia between patients with and without ipsilateral pushing. No association with side of stroke lesion was found. Ipsilateral pushing had no independent influence on gain in ADL function or discharge rate to nursing home, but patients with ipsilateral pushing used 3.6 weeks ( P Conclusions: The existence of a "pusher syndrome" was not confirmed. Ipsilateral pushing did not affect functional outcome, but showed the process of recovery considerably.

The aim of this case-control study was to test the hypothesis that women with ischemic stroke exhibit changes in their sex hormone concentrations. Cases were 149 consecutive female patients with acute

We conducted this study to determine whether the presence of aphasia at the time of acute admission impedes functional improvement of stroke patients and if chronic aphasia aggravates the detriment...

Specific neuropsychological symptoms like aphasia and neglect are well-known in stroke. General cognitive function in stroke patients has been given less attention. The Mini-Mental State Examination (MMSE) is widely used in different neurologic and psychiatric conditions. It has also been used in studies of depression with stroke and for validation of other instruments, but few studies have reported basic data con cerning MMSE in stroke. We assessed 541 unselected acute stroke patients prospec tively and consecutively with the MMSE. Its utility for functional prognosis was deter mined by multiple linear regression analyses of ADL function at discharge measured with the Barthel Index (BI), of length of rehabilitation, and by a logistic regression analysis of the rate of discharge to independent living. A considerable number of patients could not cooperate for the MMSE in the acute stage (42%, including uncon scious and aphasic patients). Reduced cognitive function was found to be common in stroke: a score ...

Aims: To investigate the roles of vascular adventitial fibroblastic cells in tumour stroma, the distribution of vascular adventitial fibroblastic cells was studied in gastric carcinomas. Methods: In total, 50 surgically resected gastric carcinomas (43 intestinal type, and seven solid type) and their normal tissues were examined. Vascular adventitial fibroblastic cells are positive for CD34 but negative for CD31. To differentiate vascular adventitial fibroblastic cells from vascular endothelial cells, immunostaining for CD34 and CD31 was performed. Immunostaining for high molecular weight caldesmon was also performed to recognise vascular media. Results: In normal gastric tissues, CD34 positive fibroblastic cells were found just outside the vascular media, namely vascular adventitial fibroblastic cells. In contrast, all of the 43 intestinal-type and seven solid-type gastric carcinomas had no vascular adventitial fibroblastic cells in the tumour stroma. Conclusions: These results suggest that a lack of vascular adventitial fibroblastic cells is associated with tumour stroma formation in intestinal-type and solid-type gastric carcinomas.

Knowledge of the frequency and remission of aphasia is essential for the rehabilitation of stroke patients and provides insight into the brain organization of language. We studied prospectively and consecutively an unselected and community-based sample of 881 patients with acute stroke. Assessment of aphasia was done at admission, weekly during the hospital stay, and at a 6-month follow-up using the aphasia score of the Scandinavian Stroke Scale. Thirty-eight percent had aphasia at the time of admission; at discharge 18% had aphasia. Sex was not a determinant of aphasia in stroke, and no sex difference in the anterior-posterior distribution of lesions was found. The remission curve was steep: Stationary language function in 95% was reached within 2 weeks in those with initial mild aphasia, within 6 weeks in those with moderate, and within 10 weeks in those with severe aphasia. A valid prognosis of aphasia could be made within 1 to 4 weeks after the stroke depending on the initial severity of aphasia. Initial severity of aphasia was the only clinically relevant predictor of aphasia outcome. Sex, handedness, and side of stroke lesion were not independent outcome predictors, and the influence of age was minimal.

The purpose of this study was to compare stroke severity, risk factors, and prognosis in patients with intracerebral hemorrhage versus infarction. We prospectively studied 1,000 unselected patients with acute stroke of a verified type in the Copenhagen Stoke Study. Neurological deficits and functional disabilities were evaluated weekly from the time of acute admission throughout the rehabilitation period. Eighty-eight (9%) had intracerebral hemorrhage. The relative frequency of intracerebral hemorrhage rose exponentially with increasing stroke severity. In multivariate analyses, stroke type had no influence on mortality, neurological outcome, functional outcome, or the time course of recovery. Initial stroke severity was the all-important prognostic factor. The relative importance of hypertension and blood pressure on admission was not greater for intracerebral hemorrhage than for infarction. No preponderance was found between type of stroke and sex, age, and smoking. Diabetes, ischemic heart disease, and elevated serum total cholesterol level all favored cerebral infarction as opposed to intracerebral hemorrhage. We conclude that the type of stroke per se has no influence on stroke prognosis in general; the extent of the injury is decisive. The poorer prognosis in patients with intracerebral hemorrhage is due to the increase in frequency of intracerebral hemorrhage with increasing stroke severity. The likelihood of cerebral infarction occurring as opposed to intracerebral hemorrhage seems increased fivefold in stroke patients with diabetes. Hypertension and blood pressure on admission were not predictors of stroke type.

Objective: To determine the time course of both neurological and functional recovery from stroke. Design: Prospective, consecutive, and community based. Setting: The stroke unit of a hospital in Copenhagen, Denmark. This setting receives all acute stroke patients admitted from a well-defined catchment area of 239,886 inhabitants within the city of Copenhagen. Acute treatment as well as all stages of rehabilitation are cared for within the stroke unit regardless of age, stroke severity, and premorbid condition. Patients: 1,197 patients with acute stroke. Main Outcome Measures: Weekly examinations of neurological deficits (using the Scandinavian Neurological Stroke Scale) and functional disabilities (Activity of Daily Living (ADL) measured by the Barthel Index) were performed from the time of acute admission to the end of rehabilitation. These evaluations were repeated 6 months poststroke. Time course of recovery was stratified according to initial stroke severity and disability. Results: Functional recovery was completed within 12.5 weeks (95% confidence interval (CI) 11.6 to 13.4) from stroke onset in 95% of the patients. However, 80% of the patients had reached their best ADL function within 6 weeks (CI 5.3 to 6.7) from onset. The time course of functional recovery was strongly related to initial stroke severity. Best ADL function was reached within 8.5 weeks (CI 8 to 9) in patients with initially mild strokes, within 13 weeks (CI 12 to 14) in patients with moderate strokes, within 17 weeks (CI 15 to 19) in patients with severe strokes, and within 20 weeks (CI 16 to 24) in patients with very severe strokes. After these time-points, no significant changes occurred. However, a valid prognosis of functional outcome can be made much earlier. Best ADL function was reached by 80% of the patients with initially mild strokes within 3 weeks (CI 2.6 to 3.4), within 7 weeks (CI 6 to 8) of the patients with moderate strokes, and within 11.5 weeks (CI 10 to 13) of the patients with severe and very severe strokes. The time course of neurological recovery followed a pattern similar to that of functional recovery, but preceeded functional recovery by 2 weeks on average. Conclusions: A reliable prognosis can in all stroke patients be made within 12 weeks from stroke onset. Even in patients with severe and very severe strokes, neurological and functional recovery should not be expected after the first 5 months.

We evaluated 38 porous-coated anatomic total knee arthroplasties in 32 patients with osteoarthritis, performed from 1985 to 1992. Anterior subsidence shown by radiographic assessment of tibial components occurred in 14 knees (36.8%), all of which were arthroplasties without cement. Anterior subsidence occurred significantly more frequently in groups in which the tibial component crossed at an almost vertical angle of 87°-90° with the tibial shaft axis in the lateral view, and also in those subjects whose bone mineral density of the distal radius (1/6 site) was low. There was a tendency for the tibial component to be covered incompletely with the anterior cortical bone of the proximal tibia.

Time course and degree of the recovery of walking function after stroke and the influence of initial lower extremity (LE) paresis were studied prospectively in a community-based population of 804 consecutive acute stroke patients. Walking function and degree of LE paresis were assessed weekly using the Barthel index and the Scandinavian Neurological Stroke scale, respectively. Initially, 51% had no walking function, 12% could walk with assistance, and 37% had independent walking function. At the end of rehabilitation, 21% had died, 18% had no walking function, 11% could walk with assistance, and 50% had independent walking function. Recovery of walking function occurs in 95% of the patients within the first 11 weeks after stroke. The time and the degree of recovery are related to both the degree of initial impairment of walking function and to the severity of LE paresis, p < .0001. A valid prognosis of walking function in patients with initially no/mild/moderate leg paresis can be made in 3 weeks, and further recovery should not be expected after 9 weeks. A valid prognosis of walking function in patients with initially severe leg paresis or paralysis can be made in 6 weeks, and further improvement of walking function should not be expected later than 11 weeks after stroke.

Although diabetes is a strong risk factor for stroke, it is still unsettled whether stroke is different in patients with and without diabetes. This is true for stroke type, stroke severity, the prognosis, and the relation between admission glucose levels and stroke severity/mortality. This community-based study included 1135 acute stroke patients (233 [20%] had diabetes). All patients were evaluated until the end of rehabilitation by weekly assessment of neurological deficits (Scandinavian Stroke Scale) and functional disabilities (Barthel Index). A computed tomographic scan was performed in 83%. The diabetic stroke patient was 3.2 years younger than the nondiabetic stroke patient (P < .001) and had hypertension more frequently (48% versus 30%, P < .0001). Intracerebral hemorrhages were six times less frequent in diabetic patients (P = .002). Initial stroke severity, lesion size, and site were comparable between the two groups. However, mortality was higher in diabetic patients (24% versus 17%, P = .03), and diabetes independently increased the relative death risk by 1.8 (95% confidence interval [CI], 1.04 to 3.19). Outcome was comparable in surviving patients with and without diabetes, but patients with diabetes recovered more slowly. Mortality increased with increasing glucose levels on admission in nondiabetic patients independent of stroke severity (odds ratio, 1.2 per 1 mmol/L; CI, 1.01 to 1.42; P = .04). This was not the case in diabetic patients. Diabetes influences stroke in several aspects: in age, in subtype, in speed of recovery, and in mortality. Increased glucose levels on admission independently increase mortality from stroke in nondiabetic but not in diabetic patients. The effect of reducing high admission glucose levels in nondiabetic stroke patients should be examined in future trials.

Twenty gastric carcinoma cases were studied for the detection of CD44 aberrant transcripts using a cDNA/PCR/blot-hybridization technique which can detect splice variants containing an aberrant exon 11 of the CD44 gene. All the tumor tissues as well as their metastatic foci demonstrated overexpression of CD44 splice variants of more than 1.0 kbp than corresponding normal gastric mucosas. Six out of nine (66.7%) well-differentiated or intestinal type gastric cancers overexpressed more than three aberrant transcripts, whereas ten out of eleven (90.9%) poorly differentiated or diffuse type cancers overexpressed single or two lower molecular weight variants. These results indicate that the detection of CD44 transcription variants can serve as a powerful tool for the diagnosis of gastric cancer. It is also suggested from the difference in variant expression pattern that well-differentiated type and poorly differentiated type gastric carcinomas have different genetic pathways.

Progression of acute stroke after arrival at hospital is frequent and the prognosis severe. However, risk factors and mechanisms behind progression are largely unknown. A prospective, community-based study of 868 patients with acute stroke was undertaken to discover factors of importance in the development of stroke in progression. Diagnosis of progression was based on the Scandinavian Neurological Stroke Scale. Patients were divided according to whether progression occurred early (within 36 hours from stroke onset) or late (within the first week from onset). Results were analysed by comparing patients with and without progression. Marked progression developed in 32%. Risk factors for early progression were identified as systolic blood pressure on admission (decreased the relative risk by 0.66 per 20 mm Hg increase, 95% CI 0.55-0.83) and diabetes (increased the relative risk by 1.9, 95% CI 1.1-3.3). Stroke severity was the only risk factor found in late progression (OR 1.4 per 20-point increase in stroke severity, 95% CI 1.1-1.7). These relations were independent of age, sex, blood glucose, heart disease, and other stroke risk factors. Early progression is related to systolic blood pressure and diabetes. Late progression is related to initial stroke severity. Although this study does not prove that a causal relationship exists between systolic blood pressure and the development of early progression, such a relationship would, however, explain our findings.

This study was undertaken to elucidate whether and how age influences stroke outcome. This prospective and community-based study comprised 515 consecutive acute stroke patients. Computed tomographic scan was performed in 79% of patients. Activities of daily living (ADL) and neurological status were assessed weekly during hospital stay using the Barthel Index (BI) and the Scandinavian Stroke Scale (SSS), respectively. Information regarding social condition and comorbidity before stroke was also registered. A multiple regression model was used to analyze the independent influence of age on stroke outcome. Age was not related to the type of stroke lesion or infarct size. However, age independently influenced initial BI (-4 points per 10 years, P < .01), initial SSS (-2 points per 10 years, P = .01), and discharge BI (-3 points per 10 years, P < .01). No independent influence of age was found regarding mortality within 3 months, discharge SSS, length of hospital stay, and discharge placement. ADL improvement was influenced independently by age (-3 points per 10 years, P < .01), whereas age had no influence on neurological improvement or on speed of recovery. Age independently influences stroke outcome selectively in ADL-related aspects (BI) but not in neurological aspects (SSS), suggesting a poorer compensatory ability in elderly stroke patients. Therefore, rehabilitation of elderly stroke patients should be focused more on ADL and compensation rather than on the recovery of neurological status, and age itself should not be a selection criterion for rehabilitation.

The aim of this study is to investigate the distribution and roles of podoplanin/D2-40-positive pericryptal stromal cells in superficial colorectal epithelial neoplasia. A total of 105 superficial colorectal epithelial tumors were examined: 65 tubular/tubulovillous adenomas, 32 adenocarcinomas in situ, and 8 submucosally invasive adenocarcinomas. Immunohistochemical analysis was performed using the monoclonal antibody to podoplanin/clone D2-40, which is reactive in both lymphatic endothelial cells and activated stromal cells, but negative in vascular endothelial cells. We found 50 (78 %) of 65 tubular/tubulovillous adenomas, 30 (94 %) of 32 adenocarcinomas in situ, and all 8 (100 %) submucosally invasive adenocarcinomas had podoplanin/D2-40-positive pericryptal stromal cells, whereas all normal colorectal mucosae had no podoplanin/D2-40-positive pericryptal stromal cells. The presence of podoplanin/D2-40-positive pericryptal stromal cells is associated with epithelial tumorigenesis in the colorectum.

A 28-year-old woman complained of irregular menstruation. Abdominal ultrasound and magnetic resonance imaging (MRI) examinations revealed a cystic tumor in the left ovary. A histological examination of the resected ovary revealed that the lesion was a mature cystic teratoma. In this tumor, components such as skin with appendages, a thyroid gland, mucosa of the digestive tract and a submandibular gland were observed. Interestingly, compound melanocytic nevus was also present in the skin component. To the best of our knowledge, this is the sixth reported case of nevus arising in a mature cystic teratoma of the ovary. Despite the extreme rarity of such a lesion, pathologists should recognize the possibility of such lesions occurring in ovarian teratoma.

Recently, significant progress in treatment of metastatic colorectal cancer has been achieved. Either FOLFIRI (fluorouracil, leucovorin and irinotecan) or modified FOLFOX6 (fluorouracil, leucovorin and oxaliplatin, oxaliplatin dose 85 mg/m(2)) is selected as first-line therapy in clinical practice in Japan. However, economic burden of colorectal cancer is considerable.Analysis was made for all patients who were treated with FOLFIRI or modified FOLFOX6 for metastatic colorectal cancer. Regimen of FOLFIRI was compared with modified FOLFOX6 under consideration from clinical and economic standpoints. Progression free survival, response, toxicity and cancer care cost in patients with metastatic colorectal cancer was analyzed. Direct costs based on the fee schedule of the Japanese national health insurance were calculated.Median progression free survival was 7.7 months for FOLFIRI versus 8.4 months for modified FOLFOX6 (P = 0.48). Overall cost for first four cycles was yen756 284 for FOLFIRI and yen1 081 162 for modified FOLFOX6 (P0.0001). All grade alopecia was significantly more frequent with FOLFIRI than with modified FOLFOX6 (P = 0.04). All grade neuropathy was more observed with modified FOLFOX6 than FOLFIRI (P = 0.0002).FOLFIRI is inexpensive in the initial stage of treatment which a number of patients can receive chemotherapy than modified FOLFOX6 as first-line therapy for metastatic colorectal cancer in Japanese national insurance system.

Wandel A, Jorgensen HS, Nakayama H, Raaschou HO, Olsen TS. Prediction of walking function in stroke patients with initial lower extremity paralysis: the Copenhagen Stroke Study. Arch Phys Med Rehabil 2000;81:736-8. Objectives: The majority of stroke patients with initial leg paralysis do not regain independent walking. We characterize the minority who, despite initial leg paralysis, regained independent walking. Design: Consecutive and community based. Setting: A stroke unit receiving all stroke patients from a well-defined community. Patients: A total of 859 acute stroke patients; 157 (15%) initially had leg paralysis. Main Outcome Measures: Scandinavian Stroke Scale (SSS) and Barthel index (BI) on admission and weekly during rehabilitation. Univariate and multivariate statistics were considered. Results: Of the 157 patients with initial leg paralysis, 84 (60%) died; 73 (40%) survived. Fifteen (21%) survivors regained walking function (the walking group), and 58 (79%) did not (the nonwalking group). The BI on admission was the only factor of significant predictive value ( p p p Conclusion: Only 10% of stroke patients with initial leg paralysis regained independent walking. In these patients, BI on admission was high and leg strength improved quickly in the first week. © 2000 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation

610 Background: Systemic chemotherapies can convert irresectable liver metastases (LM) to resectable in some cases of metastatic colorectal cancer (mCRC). Secondary surgical resection is now considered to be a worthwhile therapeutic aim in mCRC with LM. There is a clear correlation between radiological response and secondary resection rate (SRR) (Jones RP et al. Eur J Cancer 2014). However, it remains unclear which monoclonal antibodies contribute the improvement of SRR, Bmab or anti-EGFRs. Methods: We performed a systematic review of literature published between Jan 1998 and Aug 2015 to analyze the relationship between SRR and antibodies in mCRC treated with 1st-line chemotherapy. Phase II or III trials which obtained the information of response rate (RR) and resection of LM were included in this analysis. The RR, SRR, and R0 SRR were compared between Bmab- and anti-EGFR (cetuximab or panitumumab)-containing regimen groups using Mann–Whitney U test. The correlation between RR and R0 SRR was assessed by Spearman's rank correlation coefficient. Results: A total of 40 studies were enrolled: 33 treatment arms from 16 trials for liver-limited disease (LLD) and 31 arms from 24 trials for non-LLD. The result is shown below. No difference was observed in SRR and R0 SRR between Bmab and anti-EGFR groups. In addition, a preliminary analysis showed that RR had significantly positive association with R0 SRR in anti-EGFR group (R2 0.74, P=0.027 for non-LLD; R2 0.88, P=0.018 for LLD) but not in Bmab group (P=0.27 for non-LLD, P=0.12 for LLD). Conclusions: The SRR and R0 SRR were comparable between Bmab and anti-EGFRs, even in mCRC with LLD, while RR correlated with R0 SSR in anti-EGFRs but not in Bmab. These findings warrant validation in ongoing trials to compare the targeted-agents. [Table: see text]

We examined pp60c-src protein kinase activity in human gastric carcinoma cell lines and gastric carcinoma tissues as well as normal mucosa. pp60c-src kinase activity was detected in all 5 carcinoma cell lines at various levels. Of 16 gastric carcinoma tissues, 8 showed higher pp60c-src kinase activity in tumor tissues than in corresponding normal mucosa. However, the levels of expression of pp60c-src detected by Western blotting were not always consistent with the activities of pp60c-src protein kinase. These findings suggest that the increase in pp60c-src protein kinase activity might be brought about by post-translational changes.

Gastric cancer (GC) is one of the most common malignancies worldwide. Genes whose expression is down-regulated in GC may be tumour suppressor genes. In the present study, genes with decreased expression in GC were screened for by serial analysis of gene expression (SAGE) data analysis and reverse transcription (RT)-polymerase chain reaction (PCR), and CLDN18 (encoding claudin-18) was identified. Quantitative RT-PCR revealed that expression of CLDN18 was down-regulated in 13 (56.5%) of 23 GCs. Immunostaining showed that normal gastric mucosa and Paneth cells of the duodenum expressed claudin-18 on cell membranes. Expression of claudin-18 was reduced in several intestinal metaplasias of the stomach. Of 20 samples of gastric adenoma, 18 (90.0%) showed decreased claudin-18 expression. Down-regulation of claudin-18 was observed in 84 of 146 GCs (57.5%) and correlated with poor survival in 65 advanced GCs (p = 0.0346). In addition, expression of the gastric and intestinal phenotypes of GC was examined by immunostaining for MUC5AC, MUC6, MUC2, and CD10. Of 38 GCs showing only the intestinal phenotype, down-regulation of claudin-18 was observed in 28 (73.7%), whereas in the remaining 108 GC cases, down-regulation of claudin-18 was observed in 56 (51.9%) (p = 0.0224). These results indicate that claudin-18 is a good marker of poor survival in GC. Down-regulation of claudin-18 may be involved in GCs with an intestinal phenotype, and may be an early event in gastric carcinogenesis.

Gastric cancer (GC) is one of the most common malignancies worldwide. Genes expressed only in cancer tissue will be useful molecular markers for diagnosis and may also be good therapeutic targets. However, little is known about cancer-specific genes, at least in GC. In this study, we searched for GC-specific genes by serial analysis of gene expression (SAGE) data analysis and quantitative reverse transcription (RT)-PCR. Comparing GC SAGE libraries with those of various normal tissues in the SAGEmap database, we identified 54 candidate GC-specific genes. Quantitative RT-PCR analysis of these candidates revealed that APin protein (APIN), taxol resistance-associated gene 3 (TRAG3), cytochrome P450, family 2, subfamily W, polypeptide 1 (CYP2W1), melanoma inhibitory activity (MIA), matrix metalloproteinase-10 (MMP-10), dickkopf homolog 4 (DKK4), GW112, regenerating islet-derived family, member 4 (REGIV), and HORMA domain-containing 1 (HORMAD1) were expressed much more highly in GC than in 14 kinds of normal tissues. Immunohistochemical staining for MIA, MMP-10, and DKK4 was found in 47 (31.1%), 68 (45.0%), and two (1.3%) of 151 GCs, respectively, and staining for both MIA and MMP-10 was correlated with poor prognosis in advanced GC (P=0.0001 and 0.0141, respectively). Moreover, enzyme-linked immunosorbent assay showed high levels of MMP-10 (65/69, 94.2%) in serum samples from patients with GC. Levels of MIA were raised in a small proportion of serum samples from patients with GC (4/69, 5.8%). In Boyden chamber invasion assays, MIA-transfected GC cells were up to three times more invasive than cells transfected with empty vector. Taken together, these results suggest that MMP-10 is a good marker for the detection of GC and that MIA and MMP-10 are prognostic factors for GC. As expression of MIA and MMP-10 is narrowly restricted in cancer, these two molecules may be good therapeutic targets for GC.