Usefulness and accuracy of segmental adrenal venous sampling on localisation and functional diagnosis of various adrenal lesions in primary aldosteronism.

AIM: To clarify the usefulness and accuracy of segmental adrenal venous sampling (sAVS) on localisation and functional diagnosis of various adrenal lesions in primary aldosteronism. MATERIALS AND METHODS: Consecutive patients (n=162) who underwent adrenalectomy and 138 patients indicated for medication following sAVS were analysed retrospectively. Based on immunohistopathological diagnosis, the positive predictive value (PPV) of computed tomography (CT)-detectable aldosterone-producing adenoma (APA) was calculated. Moreover, endocrinological and sAVS characteristics were analysed quantitatively and qualitatively among APA, CT-undetectable aldosterone-producing nodules (APNs), multiple aldosterone-producing micronodules (MAPM), and medication groups. RESULTS: The PPV of APA by sAVS was 137/141 (97.1%; 95% confidence interval, 92.9-99.2%). Compared to the medication cases, the APA group showed stronger disease activity clinically and significant differences in adrenal hormones, such as a higher aldosterone level and aldosterone-to-cortisol ratio, and lower cortisol levels in the adrenal central vein and aldosterone maximum tributaries on the dominant side after cosyntropin stimulation. The APA group shows focal aldosterone hypersecretion, such as mean number of aldosterone elevated segments (1.7 ± 0.7 versus 2 ± 0.9, p=0.003) and presence of aldosterone-not-elevated segments (93% versus 41%, p<0.001). Clinically and in terms of sAVS, APN and MAPM showed similar characteristics to APA and to the medication cases, respectively. CONCLUSION: sAVS can localise functionally active tissues of CT-detectable and CT-undetectable lesions enabling decisions on surgical or medical treatment.

Effects of preceding endoscopic treatment on laparoscopic surgery for early rectal cancer.

AIM: Endoscopic treatment for rectal cancer, such as endoscopic mucosal resection and endoscopic submucosal dissection, causes inflammation, oedema and fibrosis in the surrounding tissue. However, little is known about the effect of these endoscopic therapies on salvage laparoscopic rectal surgery. The objective of this retrospective cohort study was to analyse the effect of preceding endoscopic treatment on the outcomes of laparoscopic surgery for rectal cancer. METHOD: We analysed 53 patients who underwent laparoscopic surgery for rectal cancer with clinical Tis or T1 at our department between May 2011 and June 2019. Data from 30 patients who underwent laparoscopic surgery after preceding endoscopic treatment (Group E + S) were compared with those of 23 patients who underwent laparoscopic surgery alone (Group S). RESULTS: There was no significant difference between the groups with respect to preoperative details. The mean operative time tended to be longer in Group E + S, and the volume of intra-operative blood loss was greater in Group E + S than in Group S (median 63 ml vs 10 ml, P = 0.049). There were no significant differences between the groups in other surgical parameters or oncological outcomes. CONCLUSION: Laparoscopic surgery after endoscopic treatment for rectal cancer may be difficult due to an increased risk of intra-operative bleeding. Long-term prognosis after surgery was not affected by preceding endoscopic treatment in rectal cancer.

Incidence of and risk factors for lymphocele formation after lateral pelvic lymph node dissection for rectal cancer: a retrospective study.

AIM: Pelvic lymphocele is a common complication that develops after pelvic lymph node dissection. The incidence of pelvic lymphocele formation has been reported to be 10.5-51% after gynaecological or urological procedures. However, no evidence has been reported thus far with regard to the development of pelvic lymphocele following lateral pelvic lymph node dissection (LPND) for low rectal cancer. The aim of this study was to investigate the incidence of and risk factors for lymphocele formation after LPND for low rectal cancer and to examine its clinical management. METHOD: We retrospectively analysed the incidence of and risk factors for pelvic lymphocele formation after LPND for rectal cancer in our hospital between January 2012 and December 2017. We also compared the size of the lymphocele between asymptomatic and symptomatic patients by using CT volumetry and examined its clinical management. RESULTS: A total of 30 out of 98 patients (30.8%) developed pelvic lymphocele after rectal LPND. The number of resected nodes was significantly higher in patients with a pelvic lymphocele (P < 0.01). The median volume was significantly higher in patients with symptomatic pelvic lymphocele (P = 0.011). Among the nine symptomatic patients, two underwent CT-guided drainage, one underwent transurethral ureteral stent placement and one underwent laparoscopic marsupialization. CONCLUSION: It is essential to keep in mind the possibility of pelvic lymphocele formation during follow-up of patients who undergo LPND, and to consider an appropriate treatment when these patients are symptomatic.

Vascular anatomy of the splenic flexure, focusing on the accessory middle colic artery and vein.

AIM: Recently, the accessory middle colic artery (AMCA) has been recognized as the vessel that supplies blood to the splenic flexure. However, the positional relationship between the AMCA and inferior mesenteric vein (IMV) has not been evaluated. Herein, we aimed to evaluate the anatomy of the AMCA and the splenic flexure vein (SFV). METHOD: Two hundred and five patients with colorectal cancer who underwent enhanced CT preoperatively were enrolled in the present study. The locations of the AMCA and IMV were evaluated, focusing on the positional relationship between the vessels and pancreas - below the pancreas or to the dorsal side of the pancreas. RESULTS: The AMCA was observed in 74 (36.1%) patients whereas the SFV was found in 177 (86.3%) patients. The left colic artery (LCA) was the major artery accompanying the SFV in 87 (42.4%) of patients. The AMCA accompanied the SFV in 65 (32.7%) patients. In 15 (7.8%) patients, no artery accompanied the SFV. The origin of the AMCA was located on the dorsal side of the pancreas in 15 (20.3%) of these 74 patients. Similarly, the destination of the IMV was located on the dorsal side of the pancreas in 65 (31.7%) of patients. CONCLUSION: The SFV was observed in most patients, and the LCA or AMCA was the common accompanying artery. In some patients these vessels were located on the dorsal side of the pancreas and not below it. Preoperative evaluation of this anatomy may be beneficial for lymph node dissection during left-sided hemicolectomy.

Utility of computed tomography and 18 F-fluorodeoxyglucose with positron emission tomography/computed tomography for distinguishing appendiceal mucocele caused by mucinous adenocarcinoma from other pathologies.

AIM: Differentiating appendiceal mucocele with mucinous adenocarcinoma from other pathologies before surgery is difficult. The objective of this study was to evaluate the utility of CT and 18 F-fluorodeoxyglucose (FDG) with positron emission tomography (PET)/CT for differentiating mucinous adenocarcinoma of appendiceal mucocele from other pathologies. METHOD: The study included 25 patients who underwent surgery for clinically diagnosed appendiceal mucoceles detected on CT at the University of Tokyo Hospital. Among these patients, 19 underwent FDG-PET/CT preoperatively. We compared features of the CT imaging findings and maximum standard uptake values (SUVmax ) detected by FDG-PET/CT between mucocele with mucinous adenocarcinoma and other pathologies. RESULTS: A total of 13 men (52%) and 12 women (48%) were included in this study, with a median age of 65 years (range 34-83). There were six patients (24%) with pathologically confirmed mucinous adenocarcinoma, 15 patients (60%) with appendiceal mucinous neoplasm and four patients (16%) with simple mucocele caused by chronic inflammation. On the CT findings, wall irregularity was the only significant feature for the two groups in this study (83.3% vs 0.0%, P < 0.01). There was a significant difference in the SUVmax levels on PET/CT between the two groups (100.0% vs 20.0%, P < 0.01). CONCLUSION: Distinguishing between mucocele with mucinous adenocarcinoma and other pathologies using imaging modalities is challenging. Our results suggest that wall irregularity on CT and elevated SUVmax on PET/CT are useful factors that can be employed for such discrimination.

Obstruction is associated with perineural invasion in T3/T4 colon cancer.

AIM: Perineural invasion (PNI) is a risk factor for recurrence and metastasis and consequently leads to decreased survival in patients with various malignancies. Recent studies showed that stent placement in obstructive colon cancer increases the frequency of PNI. We hypothesized that mechanical stress including obstruction itself may be associated with PNI. METHOD: We retrospectively reviewed 496 patients with pathological T3 or T4 colon cancer who did not receive preoperative treatment. Data were collected from medical charts and pathological findings. The relationships between PNI and other clinicopathological factors were analysed using univariate and multivariate analyses. RESULTS: PNI was observed in 239 (48%) patients. Obstruction was markedly more frequent in PNI-positive cancer (39%) than in PNI-negative cancer (24%, P = 0.0003). Multivariate analyses identified obstruction as one of the significant factors associated with PNI (OR 1.68, P = 0.028). Moreover, in 414 patients without distant metastasis who underwent complete resection, PNI was an independent factor associated with poor recurrence-free survival (hazard ratio 2.35, P = 0.003). The coexistence of PNI and obstruction resulted in greater decreases in recurrence-free survival than PNI-negative and/or non-obstructive cases. CONCLUSION: Our results suggest that obstruction is associated with PNI and consequently contributes to an increased postoperative recurrence in colon cancer.

Evaluation of the vascular anatomy of the left-sided colon focused on the accessory middle colic artery: a single-centre study of 734 patients.

AIM: Surgery for colorectal cancer located in the splenic flexure is difficult to perform because of the complex anatomy. Recently, in addition to the middle colic artery and left colic artery (LCA), the accessory middle colic artery (AMCA) has been recognized as a feeding artery for the left-sided colon. This study aimed to evaluate the vascular anatomy of the splenic flexure focusing on the AMCA in a large number of patients. METHOD: A total of 734 patients who underwent CT before surgery for colorectal cancer were enrolled. We retrospectively evaluated the vascular anatomy using both two- and three-dimensional CT angiography. RESULTS: The AMCA existed in 36.4% of the cases (n = 267). In many cases, it originated from the superior mesenteric artery (n = 228, 85.4%). The AMCA had a common trunk with the transverse pancreatic artery in 54 patients (20.2%). The frequency of the presence of the AMCA was associated with the branching pattern of the LCA, and was more frequent when the LCA was absent (P < 0.001). CONCLUSION: The presence of the AMCA is not rare and the AMCA has some branching patterns; therefore, recognizing it preoperatively and intra-operatively is important, being especially careful when the LCA is absent.

Cryopreservation of in vitro Shoot Tips of Ulluco (Ullucus tuberosus Cal.) Using D Cryo-Plate Method.

　　BACKGROUND: Maintenance of in vitro collections of ulluco (Ullucus tuberosus Cal.) is cumbersome and costly in an ex-situ genebank. An alternative method for long term preservation which is safe and cost-effective is required. OBJECTIVE: To apply a novel cryopreservation procedure using the cryo-plate system to improve the long-term conservation of ulluco. MATERIALS AND METHODS: Initially V and D cryo-plate methods were tested, subsequently the D cryo-plate method was selected for ulluco cryopreservation. The D cryo-plate procedures were optimized for post-LN regrowth procedures including cold-hardening, sucrose addition in alginate gel, and duration of LS treatment. Optimized procedures were tested with 11 ulluco lines. RESULTS: Shoot tips were isolated from cold-hardened shoots for 3-4 weeks at 5 degree C were excised to 1.0-1.5 mm long and 0.5 mm wide and precultured for 16h at 25 degree C on MS with 0.3 M sucrose. The shoot tips were attached on the cryo-plates by alginate gel with 0.4M sucrose. The cryo-plates with attached shoot tips were treated with 2.0 M glycerol and 1.0 M sucrose solution for 90 min at 25 degree C and dehydrated on filter paper in a Petri dish by air current flow at 25 degree C for 45 min before direct immersion in LN. This optimized procedure was applied to shoot tips of 11 ulluco lines, resulting regrowth ranging from 73 % to 97 %, with an average of 90 % post-LN regrowth. CONCLUSION: D cryo-plate is a practical and simple procedure for cryo-storage of in vitro grown ulluco shoot tips in an ex situ genebank.

Clear-cell carcinoma of the ovary.

Clear-cell carcinoma of the ovary (CCCO) is a distinct entity of epithelial ovarian cancer in terms of clinical, histopathological, or genetic features. The incidence of CCCO is different by ethnicity but the reason is not clear yet. Overall prognosis of CCCO is good because most CCCO is found in stage I. However, advanced disease is associated with a very poor prognosis and resistance to standard treatment. The same is true for recurrent disease. Therefore, genetic analysis of CCCO is important to find the right target(s) and better therapeutic approaches. Because of its rarity, international collaboration is necessary to conduct randomized clinical trials for CCCO.

Significance of histologic pattern of carcinoma and sarcoma components on survival outcomes of uterine carcinosarcoma.

BACKGROUND: To examine the effect of the histology of carcinoma and sarcoma components on survival outcome of uterine carcinosarcoma. PATIENTS AND METHODS: A multicenter retrospective study was conducted to examine uterine carcinosarcoma cases that underwent primary surgical staging. Archived slides were examined and histologic patterns were grouped based on carcinoma (low-grade versus high-grade) and sarcoma (homologous versus heterologous) components, correlating to clinico-pathological demographics and outcomes. RESULTS: Among 1192 cases identified, 906 cases were evaluated for histologic patterns (carcinoma/sarcoma) with high-grade/homologous (40.8%) being the most common type followed by high-grade/heterologous (30.9%), low-grade/homologous (18.0%), and low-grade/heterologous (10.3%). On multivariate analysis, high-grade/heterologous (5-year rate, 34.0%, P = 0.024) and high-grade/homologous (45.8%, P = 0.017) but not low-grade/heterologous (50.6%, P = 0.089) were independently associated with decreased progression-free survival (PFS) compared with low-grade/homologous (60.3%). In addition, older age, residual disease at surgery, large tumor, sarcoma dominance, deep myometrial invasion, lymphovascular space invasion, and advanced-stage disease were independently associated with decreased PFS (all, P < 0.01). Both postoperative chemotherapy (5-year rates, 48.6% versus 39.0%, P < 0.001) and radiotherapy (50.1% versus 44.1%, P = 0.007) were significantly associated with improved PFS in univariate analysis. However, on multivariate analysis, only postoperative chemotherapy remained an independent predictor for improved PFS [hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.27-0.43, P < 0.001]. On univariate analysis, significant treatment benefits for PFS were seen with ifosfamide for low-grade carcinoma (82.0% versus 49.8%, P = 0.001), platinum for high-grade carcinoma (46.9% versus 32.4%, P = 0.034) and homologous sarcoma (53.1% versus 38.2%, P = 0.017), and anthracycline for heterologous sarcoma (66.2% versus 39.3%, P = 0.005). Conversely, platinum, taxane, and anthracycline for low-grade carcinoma, and anthracycline for homologous sarcoma had no effect on PFS compared with non-chemotherapy group (all, P > 0.05). On multivariate analysis, ifosfamide for low-grade/homologous (HR 0.21, 95% CI 0.07-0.63, P = 0.005), platinum for high-grade/homologous (HR 0.36, 95% CI 0.22-0.60, P < 0.001), and anthracycline for high-grade/heterologous (HR 0.30, 95% CI 0.14-0.62, P = 0.001) remained independent predictors for improved PFS. Analyses of 1096 metastatic sites showed that carcinoma components tended to spread lymphatically, while sarcoma components tended to spread loco-regionally (P < 0.001). CONCLUSION: Characterization of histologic pattern provides valuable information in the management of uterine carcinosarcoma.

The identification of raft-derived tau-associated vesicles that are incorporated into immature tangles and paired helical filaments.

AIMS: Neurofibrillary tangles (NFTs), a cardinal pathological feature of neurodegenerative disorders, such as Alzheimer's disease (AD) are primarily composed of hyper-phosphorylated tau protein. Recently, several other molecules, including flotillin-1, phosphatidylinositol-4,5-bisphosphate [PtdIns(4,5)P2] and cyclin-dependent kinase 5 (CDK5), have also been revealed as constituents of NFTs. Flotillin-1 and PtdIns(4,5)P2 are considered markers of raft microdomains, whereas CDK5 is a tau kinase. Therefore, we hypothesized that NFTs have a relationship with raft domains and the tau phosphorylation that occurs within NFTs. METHODS: We investigated six cases of AD, six cases of other neurodegenerative diseases with NFTs and three control cases. We analysed the PtdIns(4,5)P2-immunopositive material in detail, using super-resolution microscopy and electron microscopy to elucidate its pattern of expression. We also investigated the spatial relationship between the PtdIns(4,5)P2-immunopositive material and tau kinases through double immunofluorescence analysis. RESULTS: Pretangles contained either paired helical filaments (PHFs) or PtdIns(4,5)P2-immunopositive small vesicles (approximately 1 µm in diameter) with nearly identical topology to granulovacuolar degeneration (GVD) bodies. Various combinations of these vesicles and GVD bodies, the latter of which are pathological hallmarks observed within the neurons of AD patients, were found concurrently in neurons. These vesicles and GVD bodies were both immunopositive not only for PtdIns(4,5)P2, but also for several tau kinases such as glycogen synthase kinase-3ß and spleen tyrosine kinase. CONCLUSIONS: These observations suggest that clusters of raft-derived vesicles that resemble GVD bodies are substructures of pretangles other than PHFs. These tau kinase-bearing vesicles are likely involved in the modification of tau protein and in NFT formation.

Measurement of small fibre pain threshold values for the early detection of diabetic polyneuropathy.

AIM: To investigate whether Aδ and C fibre pain threshold values, measured using intra-epidermal electrical stimulation (IES), in people with and without Type 2 diabetes are useful in evaluating diabetic polyneuropathy (DPN) severity. METHODS: Aδ and C fibre pain threshold values were measured in Japanese people with (n = 120) and without (n = 76) Type 2 diabetes by IES. Nerve conduction studies and other tests were performed to evaluate diabetic complications. RESULTS: Aδ and C fibre pain threshold values were high in people with diabetes compared with control subjects (Aδ fibre: 0.050 vs. 0.030 mA, P < 0.01; C fibre: 0.180 vs. 0.070 mA, P < 0.01). Participants with diabetes and neuropathy had significantly higher Aδ and C fibre pain threshold values than participants without neuropathy (Aδ fibres 0.063 vs. 0.039 mA, P < 0.01; C fibres 0.202 vs. 0.098 mA, P < 0.05). C fibre pain threshold values were significantly higher in participants with diabetes and diabetic microvascular complications than in participants without complications. Threshold values increased with complication progression. When DPN was diagnosed according to the Diabetic Neuropathy Study Group in Japan criteria, the cut-off for the C fibre pain threshold values was 0.125 mA (area under the curve 0.758, sensitivity 81.5%, specificity 61.5%). The IES test took less time (P < 0.01) and was less invasive (P < 0.01) than the nerve conduction studies. CONCLUSIONS: Intra-epidermal electrical stimulation is a non-invasive and easy measurement of small fibre pain threshold values. It may be clinically useful for C fibre measurement to diagnose early DPN as defined by the Diabetic Neuropathy Study Group in Japan criteria.

Appendiceal orifice inflammation is associated with proximal extension of disease in patients with ulcerative colitis.

AIM: Ulcerative colitis (UC) is considered to be a disease of continuous mucosal inflammation extending proximally from the rectum. However, appendiceal orifice inflammation (AOI) is a skip lesion with segments of continuous involvement from the rectum. The aim of this study was to examine the clinical characteristics and clinical course, particularly focused on proximal extension, of UC in patients with AOI. METHOD: A retrospective evaluation of patients with UC who underwent total colonoscopy at the Department of Surgical Oncology, The University of Tokyo, from 2004 to 2014. The degree of AOI was graded endoscopically as follows: 0 (no inflammation); 1 (slight oedema); 2 (moderate inflammation); and 3 (marked inflammation). A total of 189 patient records were reviewed retrospectively. The presence of AOI was analysed with regard to the clinical information of each patient, and its association with proximal extension of proctitis or left-sided colitis was evaluated. RESULTS: Of 189 patients with UC who underwent total colonoscopy at our institution, 92 were diagnosed with pancolitis, 50 with left-sided colitis and 47 with proctitis. Endoscopic findings of AOI were observed in 26 patients, including 11 (12.0%) with pancolitis, six (12.0%) with left-sided colitis and nine (19.1%) with proctitis. During follow up, proximal extension of the disease occurred in all nine patients with proctitis AOI. CONCLUSION: AOI is more frequently observed in patients with proctitis. Our results showed correlations between AOI and subsequent proximal extension of mucosal inflammation in patients with proctitis.

Clinical pattern and progression of ulcerative proctitis in the Japanese population: a retrospective study of incidence and risk factors influencing progression.

AIM: The rate of extension of proctitis in Western countries has been reported, but no data regarding long-term follow-up have been described for the Japanese population. Additionally, patients with long-standing or extensive ulcerative colitis have an increased risk for developing colorectal cancer. This study evaluated both the rate of extension of the disease and the development of neoplasia among patients with an initial diagnosis of ulcerative proctitis. METHOD: We retrospectively investigated the medical charts of patients with proctitis from 1979 to 2014. The primary focus of this research was the extension of the inflammatory area. The secondary focus included risk factors for disease extension and the development of neoplasia. RESULTS: Sixty-six patients satisfied the inclusion criteria. Proximal extension of the disease occurred in 34 patients: 19 patients had left-sided colitis and 15 had pancolitis. According to a multivariate analysis, disease extension was significantly higher in patients with disease onset before 25 years of age (P-value = 0.043). The cumulative rates of disease extension at 10 and 20 years were 33.8% and 52.2%, respectively. Three patients were diagnosed with dysplasia during follow-up, all of whom experienced disease extension before the development of dysplasia. CONCLUSION: The rate of extension of ulcerative colitis in the Japanese population was comparable to that in Western countries. A younger age of disease onset was associated with disease extension. Extension of proctitis may be associated with an increased risk of colorectal cancer.

Acquired dermal melanocytosis of the face and extremities.

Acquired dermal melanocytosis (ADM) is a relatively rare, but well-described disease among adolescent to middle-aged East Asian women, particularly those of Japanese and Chinese descent. Clinically, ADM manifests as multiple punctate and greyish-brown pigmented areas 1-3 mm in diameter occurring on both sides of the forehead and zygomatic region. The subtype of ADM affecting the face and extremities is extremely rare even in East Asian women. We describe three patients with ADM of the face and extremities (ADMFE) and their characteristic clinical features. All patients were Japanese women, and showed multiple greyish-brown pigmentations on both nasal wings and on the extensor surface of the extremities. We found that the clinical features were strikingly uniform, and that a pigmented lesion on the nasal wing can be an important clue to distinguish ADMFE from other hyperpigmented diseases of the hands and feet. One patient was treated with Q-switched ruby laser with excellent outcome. Increased awareness of ADMFE can lead to earlier diagnosis and potential treatment.

Long-term effects of post-ischaemic oestrogen on brain injury in a rat transient forebrain ischaemia model.

BACKGROUND: The current study was conducted to compare the effects of post-treatment with oestrogen on histological and neurological outcomes after short (7-day) and long (28-day) recovery periods in rats subjected to transient forebrain ischaemia. METHODS: Male Sprague-Dawley rats were randomly assigned to one of five groups: vehicle (7-day recovery period), vehicle (28-day recovery period), oestrogen (17ß-estradiol 200 µg/kg, 7-day), oestrogen (17ß-estradiol 200 µg /kg, 28-day), or sham surgical (n = 8 in each group). After forebrain ischaemia was induced with bilateral carotid artery occlusion and haemorrhagic hypotension (mean arterial pressure = 40 mmHg) for 10 min, the brain was reperfused for 7 or 28 days. Either 17ß-estradiol or vehicle was injected intravenously during the initial 2 min of reperfusion. To evaluate histological damage, the number of intact neurons per 1 mm in the hippocampal CA1 subfield was counted at 7 or 28 days after transient forebrain ischaemia. RESULTS: At 7 days after ischaemia, the number of intact neurons in the hippocampal CA1 subfield was significantly greater in the oestrogen group [57.5 (46.5)/mm: median (interquartile range)] than in the vehicle group [10 (19.5) /mm; P = 0.014]. However, there was no difference between groups at 28 days after ischaemia [vehicle: 11 (20)/mm vs. oestrogen: 6 (11)/mm]. The neurological deficit scores in the oestrogen and vehicle groups were not different from the sham group at any point post-ischaemia. CONCLUSION: The current study indicates that post-ischaemic administration of oestrogen provided short-term but not long-term neuroprotective effects in transient forebrain ischaemia in rats.

Long-term and spatial memory effects of selective ß1-antagonists after transient focal ischaemia in rats.

BACKGROUND: Although various reports have shown that ß-antagonists provide neuroprotective effects after cerebral ischaemia, their effect on spatial memory after transient focal ischaemia is not known. We investigated the treatment of ß1-antagonists on neurological outcome spatial memory for 1 month after focal cerebral ischaemia in rats. METHODS: Male rats randomly received an i.v. infusion of saline 0.5 ml h(-1), esmolol 200 µg kg(-1) min(-1), or landiolol 50 µg kg(-1) min(-1). Infusion was initiated 30 min before middle cerebral artery occlusion and continued for 24 h. The infarct areas in the hippocampus and striatum were measured after the final retention trial and neurological examinations. RESULTS: Neurological deficit scores in the landiolol- and esmolol-treated rats were significantly lower than in the control rats at 1, 4, 7, and 11 days after ischaemia (P<0.05). Using the Morris water maze to assess spatial memory, we found that escape latency and swimming path length to the platform were significantly shorter in the landiolol-treated rats, compared with the saline-treated rats at 4 and 11 days after ischaemia (P<0.05). The mean (SD) infarct area was 19.1 (8.0)% in the striatum and 18.6 (10.0)% in the hippocampus of the landiolol-treated rats, and 16.8 (14.0)% and 16.8 (15.0)% in the striatum and hippocampus, respectively, of esmolol-treated rats. This was significantly less than in control rats [striatum 31.7 (14.0)% and hippocampus 29.8 (13.0)%, P<0.05]. CONCLUSIONS: The current study indicates that although esmolol and landiolol provided long-term neuroprotection in terms of histological outcome, they had no effect on neurological outcome and spatial memory retention.