Combination therapy of cyclosporine with steroid inhibits γ-interferon and interleukin-1 gene expression at the level of mRNA synthesisin vivo

The present study examined the effect of cyclosporine (CsA) administered with steroidin vivo on the capacity of peripheral blood mononuclear cells (PBMC) from kidney transplant recipients to generate cytokines and their gene expression at the level of messenger RNA (mRNA). PBMC from CsA-prednisolone (Pred)-treated recipients displayed 66.9% inhibition (54.3±12.4 IU/ml;N=42;P<0.01) of -interferon (-IFN) production compared with normal individuals (134.6±18.6 IU/ml;N=23). Azathioprine (Az)-Pred-treated recipients displayed significantly less inhibition of -IFN generation (96.0±16.1 IU/ml;N=22;P<0.05) than CsA-treated patients. Macrophages (m) from CsA-Pred-treated recipients displayed 60.0% inhibition (5.1±0.7 U/ml;N=20;P<0.01) of interleukin-1 (IL-1) production compared with normal individuals (13.0±2.9 U/ml;N=21). These results were confirmed by the experiments using cDNA probe for -IFN or IL-1 (, ). High levels of -IFN mRNA in phytohemagglutinin (PHA)-stimulated PBMC or IL-1() mRNA in lipopolysaccharide (LPS)-stimulated m were present in normal individuals but not in CsA-treated recipients as judged by hybridization to a cloned human -IFN or IL-1() cDNA probe. These studies demonstrated that combination therapy of CsA with steroid inhibits both -IFN and IL-1 gene expression at the level of mRNA at physiological concentrations.     

Analysis of acute-phase toxicities of intensity-modulated proton therapy using a model-based approach in pharyngeal cancer patients

Pharyngeal cancer patients treated with intensity-modulated proton therapy (IMPT) using a model-based approach were retrospectively reviewed, and acute toxicities were analyzed. From June 2016 to March 2019, 15 pharyngeal (7 naso-, 5 oro- and 3 hypo-pharyngeal) cancer patients received IMPT with robust optimization. Simulation plans for IMPT and intensity-modulated X-ray therapy (IMXT) were generated before treatment. We also reviewed 127 pharyngeal cancer patients with IMXT in the same treatment period. In the simulation planning comparison, all of the normal-tissue complication probability values for dysphagia, dysgeusia, tube-feeding dependence and xerostomia were lower for IMPT than for IMXT in the 15 patients. After completing IMPT, 13 patients completed the evaluation, and 12 of these patients had a complete response. The proportions of patients who experienced grade 2 or worse acute toxicities in the IMPT and IMXT cohorts were 21.4 and 56.5% for dysphagia (P < 0.05), 46.7 and 76.3% for dysgeusia (P < 0.05), 73.3 and 62.8% for xerostomia (P = 0.43), 73.3 and 90.6% for mucositis (P = 0.08) and 66.7 and 76.4% for dermatitis (P = 0.42), respectively. Multivariate analysis revealed that IMPT was independently associated with a lower rate of grade 2 or worse dysphagia and dysgeusia. After propensity score matching, 12 pairs of IMPT and IMXT patients were selected. Dysphagia was also statistically lower in IMPT than in IMXT (P < 0.05). IMPT using a model-based approach may have clinical benefits for acute dysphagia.     

Dose-response relation and time course of

The dose-response relation of pipecuronium, the time course of its neuromuscular blocking effects, and the reversibility of the residual block by neostigmine have been investigated in patients under sevoflurane/N₂O Anesthesia using a neuromuscular transmission analyzer (Accelograph^®, Biometer, Denmark). After an initial dose of pipecuronium (0.04mg·kg^–1, i.v.), the maximum block rate, onset time, the time from administration until 25% recovery and 50% recovery of control twitch height of the first response to train-of-four nerve stimulation and the interval time of administration of maintenance dose (0.005mg·kg^–1, i.v.) were 93.7 ± 7.68%, 5.0 ± 1.84, 55.4 ± 23.92, 73.0 ± 29.44 and 38.7 ± 15.50 minutes, respectively. The average intubation score (excellent; 0, good; 1 fair; 2, poor; 3) was 0.63 ± 0.56 at the level of 95.88 ± 5.06% block. Neostigmine (1.5mg) promptly reversed the residual neuromuscular blockade induced by pipecuronium (reversal time: 10.1 ± 2.98 minutes). No side effects attributable to pipecuronium was seen in this study.In conclusion, pipecuronium is a very useful nondepolarizing neuromuscular blocking agent especially for moderately long surgical procedure over 4–5 hours.(Ueda N, Masuda Y, Muteki T, et al.: Does-response relation and time course of action of pipecuronium in patients anesthetized with nitrous oxide and sevoflurane. J Anesth 7: 151–156, 1993)     

Interleukin-6 and granulocytic elastase levels following laparoscopic cholecystectomy

Interleukin-6 (IL-6) levels have been shown to correlate well with the magnitude of surgical stress. Serum IL-6 and plasma granulocytic elastase levels, 24 h after surgery, were determined in 12 patients who underwent open major surgery [MS group; esophageal carcinoma (n=5), gastric carcinoma (n=3), colorectal carcinoma (n=4) 5 patients who had open cholecystectomy [OC group] and 17 patients who had laparoscopic cholecystectomy [LC group]. IL-6 levels correlated significantly with the duration of surgery (r=0.685,P < 0.01) and with intraoperative blood loss (r=0.583,P < 0.02). However, there was no significant correlation between granulocytic elastase and the duration of surgery or blood loss. Plasma IL-6 levels in the LC group (21±3 pg/ml) were significantly lower than those in the OC group (47±5 pg/ml) and the MS group (186±36pg/ml) (P<0.05;P<0.01). However, there was no significant difference in granulocytic elastase levels between the LC group (318±8g/l), the OC group (360±130 gmg/ml), and the MS group (701±344 g/l). Increased IL-6 levels correlated well with increased duration of surgery. The lower IL-6 levels following laparoscopic cholecystectomy may therefore be indicative of lower surgical stress associated with laparoscopic cholecystectomy.     

The role of an operating microscope in medico-legal practice

This article describes our experience in the use of a binocular surgical microscope at autopsy for the in situ forensic examination of various types of mechanical skin wounds. The microscopic image was visualised on a closed-circuit television monitor, and colour photographs and video recordings were simultaneously obtained from the monitor. With abrasions, small epidermal tags, which play a key role in the determination of external force direction, were clearly observed. With lacerations, crushing of the epidermis was observed at the wound margin, and continuous bridges of connective tissue and/or blood vessels were also found within the wound cavity. With incised wounds, the epidermis was intact up to the wound margin, and there was no continuous bridge within the wound cavity. Using these differences, it was, therefore, simple to distinguish lacerations from incised wounds. Ligature marks due to hanging were clearly observed, with petechial haemorrhages and minute abrasions readily seen in the lesion. For stab wounds caused by a single-edge knife, the morphological difference between the two ends of the wound caused by the sharp blade and the blunt side could be distinguished. It was also possible to confirm the identification of unknown cadavers by observing old wound scars using the operating microscope. Abnormal lesions of the blood vessels, such as a mechanical tear of the vertebral artery (the origin of a subarachnoid haemorrhage) and the atherosclerotic stenosis of the coronary artery, were detectable. In addition, the microscope was useful as a teaching aid to colleagues and medical students to study the nature of the wounds during or after the autopsy. We believe that this system presents advantages in terms of education and training of forensic pathologists and physicians as well as crime investigation officers.     

Postoperative mediastinitis after the coronary artery bypass grafting using internal thoracic artery graft

It has been pointed out in general that the resistance against infection is decreased in the diabetic patients. This problem is very important in patients undergoing major surgery. In cardiovascular surgery, the median wound infection may result in life threatening sequelae. We have used the internal thoracic artery as the appropriate graft for its excellent long-term patency. In this series of the diabetic patients who underwent coronary artery bypass grafting with bilateral internal thoracic artery grafts, the incidence of postoperative mediastinitis was significantly higher than other cases. Therefore the use of bilateral internal thoracic artery grafts should be avoided, if possible in the diabetic patients.     

Midterm results of bilateral enlargement of the aortic valve ring for valve replacement

From 1989, 4 patients underwent bilateral enlargement of the aortic valve ring for valve replacement. Age at the operation ranged from 2 to 8 (mean 6) years; body weight ranged from 14.9 to 25.4 (mean 19.0) kg. This procedure enabled us to implant a prosthesis 3 to 4 sizes larger (19 to 23 mm) than that measured with the native aortic annulus (13 to 17 mm). There was no late death and no cardiac event over a mean follow-up period of 6.2 years. Pressure gradient across the prosthesis measured by echocardiography was 40 mmHg in 1 patient who underwent aortic valve replacement with the use of 19 mm St. Jude Medical valve at 2 years of age. There was no significant pressure gradient in other 3 patients. All patients showed normal left ventricular function. We conclude that bilateral enlargement of the aortic valve ring for valve replacement has provided good midterm results with no mortality and no cardiac event.     

Immunocytochemical localization of aromaticl-amino acid decarboxylase and catechol-O-methyltransferase in blood vessel wall of the human dental pulp

Relatively large amounts of DOPA as compared with the concentration of norepinephrine are found in human dental pulp. AADC and COMT are localized in blood vessel walls of human dental pulp. This localization suggests a functional relationship between COMT and AADC with regard to the metabolism of DOPA.     

Vergence disorders in patients with spinocerebellar ataxia 3/Machado-Joseph disease: a synoptophore study

Diplopia, a common symptom in spinocerebellar ataxia 3/Machado-Joseph disease (SCA3/MJD) cases, is not always due to asymmetric ophthalmoplegia. We found a Japanese SCA3/MJD family, in which three patients clearly had an impairment of divergence eye movement. We thus quantitatively examined the vergence ranges in eight Japanese SCA3/MJD cases using the synoptophore test. An impairment of the vergence eye movements was found in all patients, and the vergence impairment pattern, but not the ophthalmoplegia pattern, was found to be compatible with the diplopia pattern. The diplopia in SCA3/MJD cases is, therefore, attributed, at least in part, to the impairment of the vergence eye movements.