Determining an optimal dose of linaclotide for use in Japanese patients with irritable bowel syndrome with constipation: A phase II randomized, double-blind, placebo-controlled study.

BACKGROUND: Clinical testing to determine a suitable dose of linaclotide for Japanese patients with irritable bowel syndrome with constipation (IBS-C) was needed. METHODS: This was a randomized, double-blind, placebo-controlled, dose-finding trial. Japanese patients with IBS-C diagnosed using Rome III criteria (n = 559, men/women: 49/510) were randomly assigned to 1 of 4 linaclotide doses (0.0625, 0.125, 0.25, or 0.5 mg) or placebo for the 12-week treatment period. The primary endpoint was responder rate of global assessment of relief of IBS symptoms during 12 weeks. The secondary endpoints included responder rates of complete spontaneous bowel movement (CSBM), SBM and abdominal pain/discomfort relief and others. KEY RESULTS: The primary endpoint was 23.2%, 36.2%, 38.7%, 34.8%, and 38.3% in placebo (n = 112), 0.0625 (n = 116), 0.125 (n = 111), 0.25 (n = 112), and 0.5 (n = 107) mg of linaclotide groups with the difference from the placebo group in each linaclotide group (13.0%, 15.5%, 11.6%, 15.1%, P > .05). Monthly responder rate of global assessment of relief of IBS symptoms at month 3 (48.6%), responder rate of CSBM during 12 weeks (45.8%), and responder rate of abdominal pain/discomfort relief during 12 weeks (32.7%) in the 0.5 mg were significantly higher than those in placebo group (29.5%, P < .01; 25.9%, P < .01; and 18.8%, P < .05 respectively). The most frequent adverse event in the linaclotide groups was diarrhea. CONCLUSIONS & INFERENCES: This study suggests that a linaclotide dose of 0.5 mg may be appropriate in Japanese patients with IBS-C.

Clinical Features and Outcomes of Diffuse Alveolar Hemorrhage During Antithrombotic Therapy: A Retrospective Cohort Study.

PURPOSE: Antithrombotic therapy could trigger diffuse alveolar hemorrhage (DAH), and there are several case reports of DAH that occurred during antithrombotic therapy (DAH-AT). However, little is known about the clinical features and outcomes of DAH-AT. The purpose of this study was to clarify the features and mortality of DAH-AT. METHODS: 76 consecutive patients with DAH who were admitted to our hospital between January 2003 and April 2014 were retrospectively reviewed to identify the clinical features and outcomes of DAH-AT. The primary outcome was 90-day mortality. RESULTS: Of the 76 patients with DAH, 39 patients (51 %) had DAH-AT, and 37 patients (49 %) had DAH that occurred with no antithrombotic therapy (DAH-NAT). Of the patients with DAH-AT, 25 (64 %) were taking aspirin, 14 (36 %) were taking warfarin, 5 (13 %) were taking clopidogrel sulfate, and 4 (10 %) were taking cilostazol. Pre-existing cardiac disease was present in 23 (59 %) DAH-AT cases and 5 (14 %) DAH-NAT cases. Logistic regression analysis was used to assess the effect of antithrombotic therapy on the mortality of DAH patients, and no significant difference in survival was seen with antithrombotic therapy (OR 1.18, 95 % CI 0.38-3.78). CONCLUSIONS: Antithrombotic therapies had no effect on the 90-day mortality of DAH patients.

Measurement and analysis of internal stress distributions created in gelatin simulated-brain tissue by a pulsed laser-induced liquid jet.

Transsphenoidal surgery is currently employed to treat complex lesions beyond the sella turcica; however, the procedure can be limited by difficulties encountered in dealing with small blood vessels, deep and narrow working spaces, and awkward working angles. To overcome these problems, we have developed a pulsed laser-induced liquid jet system that can dissect tumor tissue while preserving fine blood vessels within deep and narrow working spaces. We have previously evaluated the utility and safety of this procedure. However, the effects of the pulsejet after being injected into the brain are not yet well understood. Especially, the behavior of the stress distribution created by the jet is important because it has recently been reported that high acoustic pressures can affect the brain. In this study, we measured internal stress distributions in a gelatin simulated-brain using photoelasticity experiments. We used a high-speed camera with an image sensor on which an array of micropolarizers was attached to measure the stresses and the shear wave created when the pulsejet enters the simulated brain.

Analysis of liquid reservoir effect induced by pulsed laser liquid jet.

A pulsed-laser-induced liquid jet (LILJ) is a new device used in neurosurgery to simultaneously crush, incise, and aspirate tissues and tumors, preserving blood vessels and nerves. In addition, a feature of a pulsed LILJ is its ability to excavate tissue at constant depth while a liquid jet is being repeatedly focused at the same point. To clarify the mechanisms of constant depth of excavation, we employed a gelatin phantom and extracted brain tissue using a high-speed camera, and we then confirmed that the liquid-reservoir-induced LILJ played an important role in enabling the safe usage of an LILJ.

Real-time monitoring of liver damage during experimental ischaemia-reperfusion using a nitric oxide sensor.

BACKGROUND: Hepatic ischaemia-reperfusion (IR) injury may lead to liver damage during liver surgery, and intrahepatic nitric oxide (NO) levels may play a role in this context. The aim of this study was to demonstrate real-time changes in intrahepatic NO concentration during IR and to correlate potential hepatic NO production with liver damage using a selective NO sensor. METHODS: Wistar rats were exposed to 15 min of hepatic ischaemia followed by reperfusion, after which changes in intrahepatic NO levels were measured using an NO sensor. Additionally, rats were exposed to five successive periods of IR, each consisting of 15 min ischaemia followed by 5 or 15 min reperfusion, and hepatic damage was evaluated by blood tests and histological examination. Hepatic expression of Akt, phosphorylated Akt, endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS was examined at different time points during and after IR by western blot and immunohistochemical analysis. RESULTS: During ischaemia, intrahepatic NO levels increased and reached a plateau at approximately 10 min. Repeated 15 min ischaemia-5 min reperfusion cycles reduced the maximum amount of NO produced during ischaemia gradually, and almost no NO production was observed during the fifth period of ischaemia. NO production following repeated ischaemia was proportional to the degree of hepatic viability. Phosphorylated eNOS was upregulated and correlated with the level of NO production during hepatic ischaemia. CONCLUSION: Intrahepatic NO levels decrease during repeated IR in rats. Real-time monitoring of intrahepatic NO levels is useful for the prediction of IR-related liver injury during experimental liver surgery.

Bmi1 is a MYCN target gene that regulates tumorigenesis through repression of KIF1Bbeta and TSLC1 in neuroblastoma.

Recent advances in neuroblastoma (NB) research addressed that epigenetic alterations such as hypermethylation of promoter sequences, with consequent silencing of tumor-suppressor genes, can have significant roles in the tumorigenesis of NB. However, the exact role of epigenetic alterations, except for DNA hypermethylation, remains to be elucidated in NB research. In this paper, we clarified the direct binding of MYCN to Bmi1 promoter and upregulation of Bmi1 transcription by MYCN. Mutation introduction into an MYCN binding site in the Bmi1 promoter suggests that MYCN has more important roles in the transcription of Bmi1 than E2F-related Bmi1 regulation. A correlation between MYCN and polycomb protein Bmi1 expression was observed in primary NB tumors. Expression of Bmi1 resulted in the acceleration of proliferation and colony formation in NB cells. Bmi1-related inhibition of NB cell differentiation was confirmed by neurite extension assay and analysis of differentiation marker molecules. Intriguingly, the above-mentioned Bmi1-related regulation of the NB cell phenotype seems not to be mediated only by p14ARF/p16INK4a in NB cells. Expression profiling analysis using a tumor-specific cDNA microarray addressed the Bmi1-dependent repression of KIF1Bbeta and TSLC1, which have important roles in predicting the prognosis of NB. Chromatin immunoprecipitation assay showed that KIF1Bbeta and TSLC1 are direct targets of Bmi1 in NB cells. These findings suggest that MYCN induces Bmi1 expression, resulting in the repression of tumor suppressors through Polycomb group gene-mediated epigenetic chromosome modification. NB cell proliferation and differentiation seem to be partially dependent on the MYCN/Bmi1/tumor-suppressor pathways.

[Experience of chest wall reconstruction with newly developed material].

After the chest wall resection, its reconstruction is often needed. A 45-year-old male lung adenocarcinoma patient with chest wall invasion underwent upper lobectomy of the right lung with partial resection of 4-6th ribs. The size of the removed chest wall was 11 x 6.5 cm. We reconstructed the chest wall with Bard Composix E/X Mesh. This prosthesis is consisted of a polypropylene mesh and an expanded polytetrafluoroethylene sheet This material is seems to be useful in the reconstruction of chest wall in both preventing pulmonary adhesion and enabling good wound healing.

N-MYC promotes cell proliferation through a direct transactivation of neuronal leucine-rich repeat protein-1 (NLRR1) gene in neuroblastoma.

Neuronal leucine-rich repeat protein-1 (NLRR1) gene encodes a type I transmembrane protein with unknown function. We have previously described that NLRR1 gene is highly expressed in unfavorable neuroblastomas as compared with favorable tumors and its higher expression levels correlate significantly with poor clinical outcome. In this study, we have found that NLRR1 gene is one of direct target genes for N-MYC and its gene product contributes to N-MYC-dependent growth promotion in neuroblastoma. Expression levels of NLRR1 were significantly associated with those of N-MYC in various neuroblastoma cell lines as well as primary neuroblastoma tissues. Indeed, enforced expression of N-MYC resulted in a remarkable induction of the endogenous NLRR1. Consistent with these results, we have identified two functional E-boxes within the promoter region and intron 1 of NLRR1 gene. Intriguingly, c-myc also transactivated NLRR1 gene. Enforced expression of NLRR1 promoted cell proliferation and rendered cells resistant to serum deprivation. In support with these observations, small-interfering RNA-mediated knockdown of the endogenous NLRR1-reduced growth rate and sensitized cells to serum starvation. Collectively, our present findings provide a novel insight into understanding molecular mechanisms behind aggressive neuroblastoma with N-MYC amplification.

Experience with ultrasonographically guided vacuum-assisted resection of benign breast tumors.

AIM: To evaluate the feasibility and safety of vacuum-assisted resection of benign breast tumours using an 8 G handheld device. MATERIALS AND METHODS: Over a 2-year period, 22 patients with 26 breast tumours diagnosed as benign using aspiration biopsy cytology were enrolled. The mean patient age was 38 years, and the mean maximal diameter of the tumour was 13 mm. A handheld Aloka SSD 6500 ultrasonography device with a linear-type 7.5 MHz transducer was inserted into the posterior aspect of the tumour with the patient under local anaesthesia, and the tumour was resected under ultrasonographic guidance. RESULTS: This method was employed successfully in all patients, and the mean operation time was 33 min. Post-procedure complications included subcutaneous bleeding in 12 cases and haematoma in one. The pathological diagnoses were fibroadenoma in 16 cases, mastopathy in six, and tubular adenoma and pseudoangiomatous stromal hyperplasia in two cases each, respectively. Follow-up ultrasonography revealed residual tumours in four cases (15.4%). CONCLUSIONS: Although this method is feasible and safe without severe complications, it is necessary to select appropriate patients, and to obtain informed consent regarding the possibility of recurrence or residual tumour.

Securing the coronoid process during a coronoidotomy.

Sagittal application of a titanium mini screw in the coronoid process at the time of coronoidotomy is a very efficient method for easy removal.

Pulsed laser-induced liquid jet microcatheter system for rapid and reliable fibrinolysis in acute cerebral embolisms: experiments on safety and preliminary application in porcine cranial vessels.

OBJECTIVE: The authors have incorporated a holmium: YAG laser-induced liquid jet (LILJ) within a microcatheter for rapid, safe, and reliable fibrinolysis, and reported its effectiveness in vitro. The purpose of this study is to evaluate an appropriate operation mode to minimize debris size and to apply the system in in vivo experiments using a porcine cranial artery model. MATERIALS: Evaluation of debris size: The relationships between laser energy and the size of the debris have been evaluated in in vitro experiments. Pulsed LILJ (3 Hz for 60 seconds) were applied to the artificial thrombi (made out of human blood taken from healthy volunteers) in a teflon tube (internal diameter: 4 mm) in the following operation modes: firstly, the laser energy was set at 0.6, 0.8, 1.0, 1.2, 1.4 W, and urokinase (UK) solution (12000 IU/mL) was supplied at rate of 40 mL/hour. In the 0.8 W operation, the concentrations of UK were changed between 0, 1200, 6000, and 12000 lU/mL. Immediately after application of LILJ, the remnant debris were collected and fixed with formaldehyde, and the size and numbers of debris were evaluated under a light microscope. Application in a porcine cranial artery model: The acute embolic models were made using four pigs: the artificial thrombi were made of porcine blood and 1 mL of embolus was used to occlude the left lingual artery via a catheter. After occlusion of lingual artery for 30 minutes, the LILJ microcatheter system was brought to the occlusion site via a guiding catheter and with the assistance of guide-wire. After every 2.5 minutes application of LILJ, angiographies were performed to evaluate the recanalization of the occluded vessels. Cold UK (1200 IU/mL) solution (4 degrees C) was supplied at the rate of 40 mL/hour with laser operation (2 pigs) and without laser operation (2 pigs: control). The pigs were decapitated, and vessels at the laser irradiation sites were obtained to evaluate the damage to the vessel wall. RESULTS: Evaluation of debris size: After application of UK solution by the LILJ (12000 lU/mL), 48.7 (1.0 W) to 72.0% (0.8 W) of debris were under 200 microm in size, while 3.7 (0.8 W) to 17.0% (1.2 W) of them exceeded 600 microm, and the 0.8 W operation mode had a tendency to be the better operation mode. During the 0.8 W operation mode, 58 (without UK) to 72% (12000 lU/mi) of debris were under 200 microm in size, while 3.5 (12000 lU/mL) to 8.5% (without UK) of them exceeded 600 microm. Application in a porcine cranial artery model: Recanalization of the occluded vessels was obtained at 15 and 20 minutes in the treatment group. Histological specimens showed neither apparent mechanical nor thermal damage. CONCLUSION: Although an additional system to collect debris, which cannot be dealt with in the pharmacological effect of fibrinolytics in the short-term, should be developed, the present results show the possibility of the LILJ microcatheter system to become a useful assistant device for the mechanical fragmentation of embolus and the enhancement of fibrinolytics.

Development of shock wave assisted therapeutic devices and establishment of shock wave therapy.

In order to exploit systems for shock wave therapy, we are working for the development of clinical devices that are based on the concept of shock waves or related phenomena. The paper describes these new therapeutic devices designed for the minimally invasive approach to vascular thromboloysis, selective dissection of tissues, and drug or DNA delivery. To investigate the response of cells to shock loading, a precise method of shock waves generation in space and time has been developed. This method has been studied for application in cardiovascular therapy, cancer treatment, and cranioplasty in close vicinity of the brain. A laser ablation shock wave assisted particle acceleration device has been developed for delivering drug and DNA into soft targets in the human body. The penetration depth of microparticles observed in the experimental targets is believed to be sufficient for pharmacological treatments. In order to achieve an efficient method for rapid revascularization of cerebral thrombosis, a laser induced liquid jet (LILJ) system has been developed. The LILJ has been successfully applied for selective dissection of soft tissue preserving nerve and blood vessels. The system has been further improved by using piezoelectric actuators to drive the liquid jets, as an alternative to pulse laser.

Energy expenditure during walking in amputees after disarticulation of the hip. A microprocessor-controlled swing-phase control knee versus a mechanical-controlled stance-phase control knee.

We have compared the energy expenditure during walking in three patients, aged between 51 and 55 years, with unilateral disarticulation of the hip when using the mechanical-controlled stance-phase control knee (Otto Bock 3R15) and the microprocessor-controlled pneumatic swing-phase control knee (Intelligent Prosthesis, IP). All had an endoskeletal hip disarticulation prosthesis with an Otto Bock 7E7 hip and a single-axis foot. The energy expenditure was measured when walking at speeds of 30, 50, and 70 m/min. Two patients showed a decreased uptake of oxygen (energy expenditure per unit time, ml/kg/min) of between 10.3% and 39.6% when using the IP compared with the Otto Bock 3R15 at the same speeds. One did not show any significant difference in the uptake of oxygen at 30 m/min, but at 50 and 70 m/min, a decrease in uptake of between 10.5% and 11.6% was found when using the IP. The use of the IP decreased the energy expenditure of walking in these patients.

Cyclooxygenase-2 is a possible target of treatment approach in conjunction with photodynamic therapy for various disorders in skin and oral cavity.

BACKGROUND: Anti-cancer effects of cyclooxygenase (COX)-2 inhibitors have been reported, but not fully investigated in skin and oral diseases. 5-aminolaevulinic acid (ALA)-based photodynamic therapy (PDT) for treating those patients with skin and oral lesions is a highly sophisticated procedure, but the incidence of disease recurrence after treatment is rather significant. OBJECTIVE: To confirm that COX-2 could be a molecular target in adjunctive therapy to ALA-based PDT, we investigated (i) COX-2 expression in various skin and oral diseases, and (ii) the inhibitory effects on cellular growth of COX-2 selective inhibitor (nimesulide), ALA-based PDT and their combination on human oral squamous cell carcinoma (SCC) cell lines. METHODS: A total of 129 biopsy samples from the skin and oral mucosal lesions were tested immunohistochemically for COX-2 expression. Then the in vitro effects of nimesulide, ALA-based PDT, and their combination were determined on two SCC cell lines, HSC-2 and HSC-4. Three different methods (MTT assay, double-staining for annexin V and propidium iodide, caspase-3/CPP32 fluorometric protease assay) were applied for evaluation of their inhibitory effects on these two cell lines. RESULTS: Among the skin diseases, a considerable number of COX-2 high expressers were found in actinic keratosis (15 of 25, 60%), Bowen's disease (13 of 17, 76%) and extramammary Paget's disease (15 of 15, 100%). In contrast, only one of 33 (3%) basal cell carcinoma tumours was a COX-2 high expresser. Among the oral mucosal biopsies, the proportion of COX-2 high expressers increased gradually from hyperplasia (one of six, 17%) through mild dysplasia (five of eight, 63%) and moderate dysplasia (20 of 23, 87%) to severe dysplasia (two of two, 100%). Nimesulide had an inhibitory effect in vitro on HSC-2 (proven to be a COX-2 high expresser), but not on HSC-4 (a COX-2 non-expresser). While ALA-based PDT showed an inhibitory effect on both HSC-2 and HSC-4, most importantly the combination of nimesulide and ALA-based PDT demonstrated a significant synergistic effect on the cellular growth inhibition of only HSC-2, but not of HSC-4. CONCLUSIONS: Our study strongly suggests that COX-2 can be one of the molecular targets in treating various skin and oral diseases. The results from our in vitro experiments also prompt us to develop a new protocol with a combination of COX-2 selective inhibitor and ALA-based PDT for more effective treatment of those diseases.

Vestibular function and vasopressin.

OBJECTIVE: To investigate the relation between the vestibular system and vasopressin (AVP). MATERIAL AND METHODS: We examined the effects of electrical and caloric vestibular stimulation on plasma AVP levels in anesthetized rats. Plasma AVP levels of patients with intractable Ménière's disease who were subjected to endolymphatic drainage and steroid instillation surgery (EDSS) or intratympanic gentamicin (GM) injection were measured before and after these interventions. RESULTS: Electrical vestibular stimulation increased plasma AVP levels in a current intensity-dependent manner. Plasma AVP levels were also increased by caloric stimulation with cold water. Plasma AVP levels decreased rapidly after EDSS, and were maintained at a low level even 6-12 months following EDSS or intratympanic GM injection. CONCLUSIONS: Vestibular activation or inhibition-induced imbalance of intervestibular activities increased plasma AVP levels in rats. Therefore, vestibular disorder would seem to increase plasma AVP and thus worsen endolymphatic hydrops. EDSS rapidly decreased plasma AVP and would seem to reduce hydrops. Inhibition of vertigo spells by EDSS or intratympanic GM injection would reduce a possible stress response, resulting in a decrease in plasma AVP levels a long time after the treatments. This resultant decrease in AVP would beneficially inhibit the formation and/or maintenance of hydrops and thus prevent vertigo spells.

Pathology review for paediatric non-Hodgkin's lymphoma patients in Japan; a report from the Japan association of childhood leukaemia study (JACLS).

A central pathology review system with an immunophenotyping laboratory was established in Japan to support the clinical trial, the Japan Association of Childhood Leukaemia Study (JACLS) NHL-98, for patients with paediatric non-Hodgkin's lymphoma (NHL). Pathology samples from 155 clinically-suspected NHL cases were evaluated centrally initially using the Revised European-American Lymphoma (REAL) classification in a rapid review (within 2 weeks after surgery/biopsy) and then later at the consensus review (once a year). The samples were subsequently re-classified according to the new World Health Organisation (WHO) classification. After the pathology review, 96 (62%) patients were eligible for the study, and 58 of them (60%) had extra-nodal primaries. These NHL cases included B-cell lymphomas (precursor B-cell, 11; Burkitt, 18; diffuse large B-cell, 18; not otherwise specified, 3) and T/Natural Killer (NK)-cell lymphomas (precursor T-cell, 23; anaplastic large cell, 20; others, 3). There was excellent concordance in making the diagnoses (95/96, 99%) and typing (93/96, 97%) of NHL between the rapid and consensus reviews. Five cases, initially diagnosed as diffuse large B-cell lymphoma by the review, were re-classified as Burkitt lymphoma according to the immunocytochemical criteria by the WHO classification. A total of 59 (38%) cases were excluded from the study: they were Hodgkin lymphoma (7), leukaemias (11), reactive lymphoid hyperplasia (20), necrotizing lymphadenitis (7), no consensus diagnosis (1), insufficient materials (2), and others (11). This is the first report of the central pathology review from the paediatric NHL group study in Japan. Because various diseases, either neoplastic or reactive, mimicked NHL, clinically and histopathologically, the central pathology review system was critical and essential for patient enrollment and protocol assignment in our clinical trial. Through the two-step review system, highly reliable data were generated to support this study.

Usefulness of constructive interference in steady state (CISS) imaging for the diagnosis and treatment of a large extradural spinal arachnoid cyst.

We present a rare case of a symptomatic large extradural arachnoid cyst extending from the lower thoracic to sacral region in a 12-year-old boy, who presented with the signs and symptoms of spinal cord compression over 4 years. Since the pedicle of the cyst could not be delineated using conventional magnetic resonance imaging (MRI), cine-mode MRI, and computed tomography scan, partial resection of the cyst was initially performed, which significantly improved motor function. After the first operation, a single pedicle was clearly demonstrated by 3D constructive interference in steady state (CISS) MRI. Thus, additional surgery aimed at closing the dural defect was performed to prevent future enlargement of the cyst. The operative findings were consistent with those of 3D CISS imaging. Clinical and radiological features of this lesion are discussed, focusing on the usefulness of 3D CISS MRI for preoperative evaluation, and especially for delineating the pedicle in cases of large extradural spinal arachnoid cysts.

Intraoperative thermal artery imaging of an EC-IC bypass in beagles with infrared camera with detectable wave-length band of 7-14 microm: possibilities as novel blood flow monitoring system.

OBJECTIVE: In the past, the usefulness of thermal arterial imaging during coronary bypass surgery using an infrared camera has been reported by several investigators. The goal of this study is to apply this novel imaging system for intraoperative arterial imaging, as well as to develop new utilizations for a neurosurgical procedure. MATERIALS: We have attempted real-time imaging of anastomotic and flow status in an external carotid-internal carotid artery (EC-IC) bypass surgery using a new-generation infrared camera (IRIS IV thermographic imaging system) in beagles. No contrast medium or radiation was used to obtain the images. The detectable wave-length band of the infrared lens was 7-14 microm. After completion of bypass monitoring, an additional teflon tube was inserted into a branch of the STA to inject physiological saline of different temperatures to see the changes in cortical images. RESULTS: Anastomotic and flow status were clearly visualized throughout the operation without local surface cooling, which had been an inevitable procedure in coronary imaging to make a pronounced temperature difference between artery and adjacent tissue. In addition, cortical flow territory was visualized after injection of either cold or warm physiologic saline into the artery from an additionally inserted teflon tube into a branch of STA via bypass artery. CONCLUSION: From the present experience, it is considered that infrared imaging using a detectable wave length band of 7-14 microm may be applicable to a wide variety of near surface lesions, providing a non-invasive functional angiography.

Pulsed liquid jet dissector using holmium:YAG laser--a novel neurosurgical device for brain incision without impairing vessels.

BACKGROUND: Neurosurgery has long required a method for dissecting brain tissue without damaging principal vessels and adjacent tissue, so as to prevent neurological complications after operation. In this study we constructed a prototype of such a device and used it in an attempt to resect beagle brain cortex. METHOD: The prototype device consisted of an optical fibre, a Y adaptor, and a nozzle whose internal exit diameter was 100 microm. Cold physiological saline (4 degrees C) was supplied to it at a rate of 40 ml/h. Pulsed liquid jets were ejected from the nozzle by a pulsed Holmium:YAG) (Ho:YAG) laser at an irradiation energy of 300 mJ/pulse. The profile of the liquid jet was observed with a high-speed camera while changing the distance between the optical fibre end and nozzle exit (equivalent to the standoff distance). With this device (3 Hz operation), brain dissection of anaesthetized beagles was attempted while measuring the local temperature of the target. A histological study of the incised parts was also performed. FINDINGS: When the standoff distance was 24 mm, the liquid jet was emitted straight from the nozzle at a maximum initial velocity of 50 m/s. The brain parenchyma was cut with this device while preserving vessels larger than 200 microm in diameter and keeping the operative field clear. The local temperature rose to no more than 41 degrees C, below the functional heat damage threshold of brain tissue. Histological findings showed no signs of thermal tissue damage around the dissected margin. INTERPRETATION: The Ho:YAG laser-induced liquid jet dissector can be applied to neurosurgery after incorporating some minor improvements.