Comparison between dexmedetomidine and midazolam as a sedation agent with local anesthesia in inguinal hernia repair: randomized controlled trial.

PURPOSE: In Japan, inguinal hernia repair is widely performed with local anesthesia. The objective of this study was to evaluate safety and efficacy of intravenous dexmedetomidine as a sedation agent with local anesthesia in inguinal hernia repair. METHODS: We performed this randomized, single-blind study for 200 patients who were scheduled to undergo inguinal hernia repair with local anesthesia. Patients were randomly divided into two groups (dexmedetomidine group: Group D, midazolam group: Group M). The primary outcome was to evaluate the safety of intravenous dexmedetomidine. Secondary outcomes were to analyze results of operators' surveys and patients' questionnaires and evaluate implementation of conscious sedation. RESULTS: Incidence of respiratory depression was significantly higher in Group M than Group D (p = 0.03). Other adverse events examined did not differ significantly. All three operators' questionnaires indicated that results were better in Group D than Group M. More than 70% of patients in both groups were satisfied with the surgery. More than 80% of Group D patients and 74% of Group M patients achieved a state of conscious sedation. CONCLUSION: This study demonstrated that intravenous dexmedetomidine during hernia repair with local anesthesia is safe and the results were satisfactory to both operators and patients.

Early results of multicenter phase II trial of perioperative oxaliplatin and capecitabine without radiotherapy for high-risk rectal cancer: CORONA I study.

BACKGROUNDS: Perioperative introduction of developed chemotherapy into the treatment strategy for locally advanced rectal cancer (LARC) may be a promising option. However, the most prevalent treatment for high-risk LARC remains preoperative chemoradiotherapy (CRT) in Western countries. PATIENTS AND METHODS: A phase II trial was undertaken to evaluate safety and efficacy of perioperative XELOX without radiotherapy (RT) for patients with high-risk LARC. Patients received 4 cycles of XELOX before and after surgery, respectively. Primary endpoint was disease-free survival. RESULTS: We enrolled 41 patients between June 2012 and April 2014. The completion rate of the preoperative XELOX was 90.3%. Twenty-nine patients (70.7%) could start postoperative XELOX, 15 of these patients (51.7%) completed 4 cycles. Allergic reaction to oxaliplatin was experienced by 5 patients (17.2%) during postoperative XELOX. One patient received additional RT after preoperative XELOX. Consequently, the remaining 40 patients underwent primary resection. Major complications occurred in 6 of 40 patients (15.0%). Pathological complete response (pCR) rate was 12.2%, and good tumor regression was exhibited in 31.7%. N down-staging (cN+ to ypN0) and T down-staging were detected in 56.7% and 52.5%, respectively. Clinical T4 tumor was a predictor of poor pathological response (p < 0.001). CONCLUSIONS: We could show the favorable pCR rate after preoperative XELOX alone. However, the T and N down-staging rate was likely to be insufficient. When tumor regression is essential for curative resection, the use of preoperative CRT is likely to be recommended. For patients with massive LN metastasis, the additional Bev to NAC might be a promising option.

Mesenteric phlebosclerosis associated with long-term oral intake of geniposide, an ingredient of herbal medicine.

BACKGROUND: Idiopathic mesenteric phlebosclerosis (IMP) is a rare disease, characterised by thickening of the wall of the right hemicolon with calcification of mesenteric veins. However, the aetiology remains unknown. AIM: To investigate the possible association of herbal medicines with IMP. METHOD: The clinical data of four of our own patients were collected. Furthermore, we searched for previous reports about similar patients with detailed descriptions of herbal prescriptions that they had taken. We compared herbal ingredients to identify the toxic agent as a possible aetiological factor. RESULTS: Clinical data on a total of 25 patients were summarised. Mean age was 61.8 years and there was female predominance (6 men and 19 women). The used Kampo prescription, the number of cases, and the mean duration of use were as follows: kamisyoyosan in 12 cases for 12.8 years, inshin-iseihaito in 5 cases for 13.4 years, orengedokuto in 4 cases for 14.3 years, inchinkoto in 1 case for 20 years, kamikihitou in 1 case for 19 years, seijobofuto in 1 case for 10 years and gorinsan in 1 case for an unknown duration. Only one ingredient, sansisi, was common to the herbal medicines of all 25 patients. This crude drug called geniposide in English is a major constituent of the Gardenia fruits. CONCLUSION: The long-term use of geniposide in herbal medicines appears to be associated with mesenteric phlebosclerosis.

Psychophysiological correlates of social skills deficits in persons with schizophrenia.

Social skill deficits in schizophrenia profoundly affect patients' life-long outcome, although the profile of the underlying cognitive dysfunction still remains a matter of debate. In the present study, we investigated the relationship between social skills and event-related potentials (ERPs) in an auditory selective attention task, in addition to the neurocognitive indices obtained from the degraded-stimulus continuous performance test (CPT) and clinical indices, such as Brief Psychiatric Rating Scale (BRPS) and global assessment of function (GAF) scores. Social skills were assessed using a Japanese version of the structured role play test. Fourteen persons with schizophrenia participated in the study. Non-verbal skills showed a positive correlation with GAF, the performance level, N1 and N2b amplitude in the ERP task, and hit rate in the CPT, and a negative correlation with reaction time in the CPT. Verbal communication skills showed a positive correlation with GAF, the performance level and N2b amplitude in the ERP task, and hit rate in the CPT, and a negative correlation with reaction time in the CPT. Processing skills showed a positive correlation with the performance level and N1 amplitude in the ERP task and a negative correlation with reaction time in the CPT. These findings suggested that the social skill deficits of persons with schizophrenia were related to the vigilance level and controlled stimulus detection processing.

Vancomycin-intermediate Staphylococcus aureus in Korea.

Recent reports on some methicillin-resistant Staphylococcus aureus (MRSA) with reduced susceptibility to vancomycin have been a major concern in Korea because of the widespread use of vancomycin due to a high prevalence of MRSA in the country. We describe a 45-year-old man with long-standing pelvic abscess due to MRSA. In spite of vancomycin and teicoplanin treatment for a long period of time, the patient died from MRSA sepsis. The blood culture isolate of MRSA exhibited reduced susceptibility to vancomycin (MIC, 8 microg/ml). This is the first report of a vancomycin-intermediate S. aureus case from Korea.

Preoperative systemic 5-fluorouracil does not increase the risk of liver resection.

BACKGROUND/AIMS: The majority of patients who underwent surgery for colorectal liver metastases have been previously treated with 5-FU either as adjuvant chemotherapy or as a primary treatment. We have performed a retrospective study to assess whether this chemotherapy increases the risk of liver resection. METHODOLOGY: Mortality, morbidity and histology of the resected liver of two groups of patients having colorectal liver metastases who underwent major resection were studied. The first group included 17 patients who had received at least 2 courses of 5-FU chemotherapy within 3 months prior to liver resection. The second group included 18 patients who had received no chemotherapy and who were used as controls. RESULTS: Perioperative mortality was nil. Intraoperative blood loss during liver resection (1 +/- 2.5 vs. 1.2 +/- 2 units) was similar in the two groups. Changes of liver function tests on days 2 and 5 were similar in the two groups. Morbidity rate was similar in the two groups (29 vs. 22%) with a mean duration of postoperative hospital stay of 19 +/- 9 days in the 5-FU group and 16 +/- 6 days in the control group. Although 7 (41%) patients in the 5-FU group had an abnormal parenchyma consistency as compared to only 3 (17%) in the control group, the pathological findings within the resected specimen were not different. CONCLUSIONS: 5-FU based systemic chemotherapy does not increase the risk of liver resections.

Bronchopulmonary arterial anastomosis at the precapillary level in human lung. Visualization using CT angiography compared with microangiography of autopsied lung.

PURPOSE: To investigate the interrelationships between the bronchial and pulmonary circulations including the existence of precapillary bronchopulmonary arterial anastomoses. MATERIAL AND METHODS: CT of bronchial arteriography (BAG-CT) was performed in 10 patients and BAG-CT during a pulmonary artery block test (PA-block) in 5 patients with lung cancer. Bronchial and pulmonary circulations were evaluated in 5 autopsied normal lungs by injecting silicone rubber with different colors into the bronchial and pulmonary arteries. RESULTS: BAG-CT correlated well with the findings at silicone rubber injection into lung autopsy samples. BAG-CT demonstrated inflow of contrast medium into the pulmonary artery during PA-block in all cases, while no inflow was observed before and following reversal of PA-block. Mixed silicone rubber was observed in the lobar to subsubsegmental bronchial arteries in all cases and in the subsubsegmental pulmonary artery in one case. CONCLUSION: Precapillary bronchopulmonary arterial anastomoses may exist at the level of the lobar bronchi to the periphery. If either the pulmonary or bronchial circulation is disturbed, flow occurs inside the anastomoses to supplement the other flow, especially flow from the bronchial to the pulmonary arteries via the anastomoses, which occurs within 30 min.

Multiple generators in the auditory automatic discrimination process in humans.

To reveal the spatiotemporal characteristics of the auditory automatic discrimination process, mismatch negativity (MMN) generators were assessed with a high-resolution EEG system (128ch) and scalp current density (SCD) analysis. Ten normal volunteers participated in the study. Event-related potentials were recorded during a selective attention task. Sequential SCD mappings revealed that a current sink/source combination in the left temporal regions and a current sink in the right frontotemporal regions appeared around 200 msec irrespective of the ear of stimulation. Moreover, a parietal sink/source combination was demonstrated on the right hemisphere around 240 ms irrespective of the ear of stimulation. These findings demonstrate that the auditory automatic change detection process is, both spatially and temporally, a multiple-generated system.

Mismatch negativity and N2b attenuation as an indicator for dysfunction of the preattentive and controlled processing for deviance detection in schizophrenia: a topographic event-related potential study.

The present study compares the amplitudes and topographic patterns of mismatch negativity (MMN) and N2b in schizophrenic patients and normal controls. Twenty-one schizophrenic outpatients and 19 normal volunteers participated in the study. Event-related potentials (ERPs) were recorded in a selective attention task. During the task, subjects were required to focus on one ear, counting deviant stimuli, those deviating in duration from a sequence of standard stimuli. MMN was significantly attenuated in the schizophrenics as compared with the normals in the frontocentral regions. In addition to MMN, the N2b amplitude was also reduced, which showed a significant correlation with the MMN amplitude in the schizophrenics. The late negativity elicited by the deviant stimuli in the unattended condition showed different topographical features between the groups. Whereas the normals showed a lateralized distribution with an ear-related asymmetry, similar to that of the N2b, the schizophrenics showed a frontal dominance, coinciding with the sustained negativity reported by Näätänen et al. (1982), which reflects the automatic preparation for detecting possible subsequent stimulus changes. The amplitude of the sustained negativity was significantly correlated with the performance level in the schizophrenics. The results indicated that although both preattentive and controlled processings are impaired, schizophrenic patients, presumably due to the deficient controlled processing, owe much to automatic processing in the deviant stimulus detection process.

Effect of antimicrobial agents on the piliation of Pseudomonas aeruginosa and adherence to mouse tracheal epithelium.

The effect of subminimal inhibitory concentrations (sub-MICs) of antimicrobial agents on the adherence of Pseudomonas aeruginosa (pili+) to trachea mucosal cells, the first stage in the development of P. aeruginosa respiratory tract infections, was investigated. The adherence of P. aeruginosa to the cells of the lower respiratory tract using a model of acid-injured trachea in mice was observed by electron microscopy (transmission and scanning). When P. aeruginosa was cultured with 1/4 MIC of erythromycin, minocycline, clindamycin, ofloxacin or tobramycin at 37 degrees C for 4 hours, the number of pili was significantly reduced (P < 0.01), together with a significant reduction in the number of adherent bacteria at 1/4 MIC of erythromycin (P < 0.01). No suppressive effects of piperacillin or ceftazidime were obtained on the piliation and adhesion of P. aeruginosa. These findings indicate that sub-MICs of erythromycin reduce the adherence of P. aeruginosa to the tracheal mucosa, which may prevent the onset of P. aeruginosa respiratory tract infection.

Changes in the basal ganglia and thalamus following reperfusion after complete cerebral ischaemia.

We report specific changes bilaterally in the basal ganglia and thalamus following reperfusion after complete cerebral ischaemia. A 69-year-old man, resuscitated after cardiac arrest, showed symmetrical low-density lesions in the head of the caudate nucleus and lentiform nucleus on CT. MRI revealed methaemoglobin derived from minor haemorrhage in the basal ganglia and thalamus, not evident on CT. We suggest that this haemorrhage results from diapedesis of red blood cells through the damaged capillary endothelium following reperfusion.

Specific changes in human brain following reperfusion after cardiac arrest.

BACKGROUND AND PURPOSE: Very few reports are available on serial changes in human brain after cardiac arrest. The primary objective of this study is to investigate sequential neuroradiological changes in patients remaining in a persistent vegetative state following resuscitation after cardiac arrest. METHODS: We repeatedly studied eight vegetative patients resuscitated from unexpected out-of-hospital cardiac arrest using computed tomographic (CT) scanning and high-field magnetic resonance (MR) imaging at 1.5 T. RESULTS: In seven of the eight patients, CT scans obtained between days 2 and 6 features symmetrical low-density lesions in the bilateral caudate, lenticular, and/or thalamic nuclei. These ischemic lesions were persistently of low density on serial CT scans. In these seven patients, MR images demonstrated what were thought to be hemoglobin degradation products derived from minor hemorrhages localized in the bilateral basal ganglia, thalami, and/or substantia nigra. Diffuse brain edema in the acute stage and diffuse brain atrophy in the chronic stage were consistent neuroradiological findings. No abnormal enhanced lesions were demonstrated by CT scans. CONCLUSIONS: The most characteristic findings on high-field MR images were symmetrical lesions in the bilateral basal ganglia, thalami, and/or substantia nigra with specific changes suggestive of minor hemorrhages that were not evident on CT scans. We speculate that these minor hemorrhages result from diapedesis of red blood cells in these regions during the reperfusion period through the endothelium disrupted by ischemia-reperfusion insult.

Pathological studies on local tissue reactions in guinea pigs and rats caused by four different adjuvants.

We investigated pathological changes at the injection site in guinea pigs and rats for 16 weeks following a single intramuscular injection of one of the following oil adjuvant emulsions; oil adjuvant ISA-70, Freund's incomplete adjuvant, Freund's complete adjuvant, and aluminium phosphate gel. In the animals injected with ISA-70 emulsion prepared by manual shaking, grossly, there was partial thickening of subcutaneous tissue, discoloration of inter-muscular connective tissue, and swelling of the inguinal lymph nodes at 2 and 4 weeks post injection (PI). Histopathologically, ISA-70 injected sites revealed acute inflammatory changes at 72 hrs PI, and peak reactions consisting of macrophage accumulation around oil cysts and fibrosis were observed at 4 weeks PI. These changes were less severe and of shorter duration than those in the other three adjuvants. Guinea pigs and rats injected with materials containing inactivated Newcastle disease virus (NDV) antigen similarly showed an infiltration of plasma cells and lymphocytes in addition to the changes described above. ISA-70 containing NDV antigen induced similar hemagglutination-inhibition titer to that induced by Freund's incomplete adjuvant.

Transcatheter hepatic arterial chemoembolization using epirubicin-lipiodol: experimental and pharmacological evaluation.

The experimental and pharmacological characteristics of various formulations of an anticancer agent (epirubicin, EPI) and lipiodol were evaluated in vitro and in vivo. Three forms of EPI-lipiodol, i.e., an oil-in-water type of emulsion (O/W type), a water-in-oil type of emulsion (W/O type), and a suspension (S type), were prepared and investigated for their stability. An O/W-type emulsion using a stock solution of Iopamidol as the solvent for EPI was the most stable form in the stationary state in vitro. In 16 patients with malignant liver tumors (14 hepatocellular carcinomas and 2 liver metastases), the three forms of EPI-lipiodol were injected into the proper hepatic artery. The plasma EPI level was monitored periodically and analyzed pharmacokinetically. No significant difference in the pharmacokinetics of EPI was detected among the O/W, W/O, and S types.

Increased sensitivity of the thyrotroph to thyrotropin-releasing hormones in rats with hypothalamic hypothyroidism.

The status of TSH secretion in hypothalamic hypothyroidism was evaluated by using rats with anterior medial basal hypothalamic deafferentation as the experimental model of the disorder. In the deafferented rats, the basal serum thyroid hormone concentrations as well as that of TSH was significantly lower than normal and cold exposure failed to increase serum TSH, indicating they were in fact in a hypothalamic hypothyroid state. The minimum effective dose of TRH to elicit an increase in serum TSH was smaller in the deafferented rats than in the controls, whereas the response to the maximum dose of TRH was similar in both groups. Although the radioimmunoassayable TSH of the adenohypophysis was significantly decreased in the deafferented rats, it was qualitatively similar to that of the control rats, since the peak of TSH immunoreactivity was eluted at exactly the same position on the gel filtration column in the pituitaries from normal and deafferented rats. When the adenohypophysis was perifused in vitro with Krebs-Ringer solution buffered with Hepes, the minimum effective dose of TRH was similar in both cases. This finding suggests that the exposure to the perifusion medium completely devoid of thyroid and hypothalamic hormones erased the difference in sensitivity to TRH between the two groups as observed in vivo, although in vivo experiments on deafferented rats with normal thyroid hormone induced by exogenous thyroid hormone were not performed. Our results indicate that in hypothalamic hypothyroid rats: 1) the sensitivity but not the responsiveness of the thyrotroph to TRH is increased; and 2) the readily releasable fraction of pituitary TSH pool in response to exogenous TRH is increased. It is also suggested that the difference in the milieu between the pituitary of normal and deafferented rats in vivo is critically important for the latter to retain hypersensitivity to TRH.