CD24, not CD47, negatively impacts upon response to PD-1/L1 inhibitors in non-small-cell lung cancer with PD-L1 tumor proportion score < 50.

CD24, a heavily glycosylated glycosylphosphatidylinositol-anchored surface protein, inhibits phagocytosis as potently as CD47. The relationship between such anti-phagocytic factors and the immune response with immune-checkpoint inhibitors (ICI) remains unexplored. We evaluated CD24 and CD47 tumor proportion scores (TPS) in 68 of the 106 patients with advanced non-small-cell lung cancer who participated in a prospective observational study of ICI treatment. We also explored the impact of CD24 TPS and CD47 TPS on ICI efficacy and serum cytokine changes. CD24 positivity (TPS ≥ 1) was negatively associated with progression-free survival (PFS) of ICI when PD-L1 TPS was < 50 (median PFS; 37 vs 127 d, P = .033), but there was no association when PD-L1 TPS was ≥ 50 (median PFS; 494 vs 144 d, P = .168). CD24 positivity was also related to significantly higher increase of CCL2 from baseline to 4-6 wk later, and such increase was notably observed only when PD-L1 TPS < 50 (P = .0004). CCL2 increase after ICI initiation was negatively predictive for survival after initiation of ICI (median survival time; not reached vs 233 d; P = .028). CD47 TPS high (≥60) significantly suppressed the increase in vascular endothelial growth factor (VEGF)-A, D and PDGF-AB/BB after ICI initiation. There was no association, however, between CD47 tumor expression and the efficacy of ICI. In conclusion, CD24, not CD47, is a candidate negative predictive marker of ICI in advanced, non-small-cell lung cancer with PD-L1 TPS < 50. Tumor expression of both CD24 and CD47 was associated with changes in factors related to monocytes and angiogenesis after ICI initiation (UMIN000024414).

The increased frequency of methicillin-resistant Staphylococcus aureus with low MIC of beta-lactam antibiotics isolated from hospitalized patients.

Methicillin-resistant Staphylococcus aureus (MRSA) causes severe infectious diseases and can be life-threatening in healthcare-settings. MRSA is classified into health-care associated (HA)-MRSA strains and community acquired (CA)-MRSA strains based on genotype and phenotype. CA-MRSA has been reported to show the lower minimal inhibitory concentration (MIC) of some antibiotics as compared to HA-MRSA. Recently, the prevalence of CA-MRSA has been increased in worldwide. CA-MRSA is isolated not only from the healthy individuals in a community but also from the patients in healthcare settings. However, the changing trend in frequency of HA-MRSA and CA-MRSA in the hospital setting is not clear. Therefore, we analyzed the trend of MIC to speculate the frequency of HA-MRSA and CA-MRSA in the facility. Moreover, gene mutations were evaluated on resistant gene loci with next generation sequencer. The frequency of strains with low MIC of beta-lactam antibiotics was gradually increased in isolated MRSA strains from the hospitalized patients. Whole genome analysis revealed the frequency of gene mutation was also decreased in some resistant loci, such as blaZ and blaR1. These findings highlight the changing trend of MRSA strains isolated from hospitalized patients.

Erythropoietin signal protected human umbilical vein endothelial cells from high glucose-induced injury.

AIM: High glucose (HG) induces endothelial injury in vasculature, leading to tissue injury in diabetic condition. Therefore, diabetes is one of the major cause of end-stage kidney disease as well as cardiovascular diseases. Chronic inflammation is involved in the progression of HG-induced cell injury. Recently, it has been reported that erythropoietin (EPO) protects the tissues from some kind of injury, such as hypoxia and mechanical stress. However, the contribution of EPO to HG-induced tissue injury remains to be explored. Therefore, we hypothesized that EPO protects endothelial cells from HG-induced injury via the regulation of inflammatory and anti-inflammatory balance. METHODS: We performed genome-wide transcriptome profiling in human umbilical vein endothelial cells (HUVEC), which were stimulated by HG with/without EPO treatment and detected the expression of inflammation associated genes. RESULTS: The expression pattern of mRNA expression in HG stimulated HUVEC with/without EPO were different in hieralchial clustering analysis. While inflammatory cytokines/chemokines mRNA expression were increased by the HG stimulation in HUVEC, Th2-related cytokine receptors and intracellular signaling molecules showed the reduced mRNA expression levels. EPO treatment reduced inflammatory cytokines/chemokines mRNA expression and increased Th2-related cytokine mRNA expression levels. Moreover, EPO stimulation increased mRNA expression of EPO receptor and ß-common receptor. CONCLUSION: EPO signaling protects HG-induced cell injury by the regulation of immune balance.

Usefulness of laparoscopic subtotal cholecystectomy with operative cholangiography for severe cholecystitis.

PURPOSE: Cholecystectomy can become hazardous when inflammation develops, leading to anatomical changes in Calot's triangle. We attempted to study the safety and efficacy of laparoscopic subtotal cholecystectomy (LSC) to decrease the incidence of complications and the rate of conversion to open surgery. METHODS: Patients who underwent LSC between January 2005 and December 2008 were evaluated retrospectively. The operations were performed laparoscopically irrespective of the grade of inflammation estimated preoperatively. However, patients with severe inflammation of the gallbladder underwent LSC involving resection of the anterior wall of the gallbladder, removal of all stones and placement of an infrahepatic drainage tube. To prevent intraoperative complications, including bile duct injury, intraoperative cholangiography was performed. RESULTS: LSC was performed in 26 elective procedures among 26 patients (eight females, 18 males). The median patient age was 69 years (range 43-82 years). The median operative time was 125 min (range 60-215 min) and the median postoperative inpatient stay was 6 days (range 3-21 days). Cholangiography was performed during surgery in 24 patients. One patient underwent postoperative endoscopic sphincterotomy for a retained common bile duct stone that was found on cholangiography during surgery. Neither complications nor conversion to open surgery were encountered in this study. CONCLUSIONS: LSC with the aid of intraoperative cholangiography is a safe and effective treatment for severe cholecystitis.

Intra-Brain and Plasma Levels of L-Serine Are Associated with Cognitive Status in Patients with Chronic Kidney Disease.

Introduction: The number of patients with chronic kidney disease (CKD) is increasing worldwide. Cognitive impairment is one of the comorbidities of CKD. With the increased number of aged population, novel biomarkers of impaired cognitive function are required. Intra-body profile of amino acid (AA) is reportedly altered in patients with CKD. Although some AAs act as neurotransmitters in the brain, it is not clear whether altered AA profile are associated with cognitive function in patients with CKD. Therefore, intra-brain and plasma levels of AAs are evaluated with respect to cognitive function in patients with CKD. Methods: Plasma levels of AAs were compared between 14 patients with CKD, including 8 patients with diabetic kidney disease, and 12 healthy controls to identify the alteration of specific AAs in CKD. Then, these AAs were evaluated in the brains of 42 patients with brain tumor using non-tumor lesion of the resected brain. Cognitive function is analyzed with respect to intra-brain levels of AAs and kidney function. Moreover, plasma AAs were analyzed in 32 hemodialyzed patients with/without dementia. Results: In patients with CKD, plasma levels of asparagine (Asn), serine (Ser), alanine (Ala), and proline (Pro) were increased as compared to patients without CKD. Among these AAs, L-Ser, L-Ala, and D-Ser show higher levels than the other AAs in the brain. Intra-brain levels of L-Ser was correlated with cognitive function and kidney function. The number of D-amino acid oxidase or serine racemase-positive cells was not correlated with kidney function. Moreover, the plasma levels of L-Ser are also decreased in patients with declined cognitive function who are treated with chronic hemodialysis. Conclusion: The decreased levels of L-Ser are associated with impaired cognitive function in CKD patients. Especially, plasma L-Ser levels may have a potential for novel biomarker of impaired cognitive function in patients with hemodialysis.

Acute respiratory distress syndrome after gastrointestinal surgery.

BACKGROUND/AIMS: Acute respiratory distress syndrome (ARDS) occasionally occurs after gastrointestinal surgery involving severe inflammation such as diffuse peritonitis. Management of this condition has been difficult and effective therapies have not yet been established. In the present study the management for ARDS after gastrointestinal surgery was evaluated. METHODOLOGY: A total of 15 patients developed ARDS after gastrointestinal operations performed in our institution. The mean patient age was 75.4±11.1 years. Onset of ARDS occurred ≤24 hours postoperatively in 12 patients and 3- 11 days postoperatively in 3 patients. Treatment for ARDS comprised continuous hemodiafiltration (CHDF), high-dose glucocorticoid therapy or administration of a neutrophil elastase inhibitor (sivelestat). RESULTS: Four patients died 3-45 days after onset of ARDS (mortality rate, 26.6%). CHDF was performed in 12 patients, 8 patients received highdose glucocorticoid therapy and 11 patients received sivelestat. No differences in severity scores and clinical data were noted between survivors and non-survivors. PaO2/FiO2 ratio was significantly lower in non-survivors than in survivors from 5 days after starting treatment, whereas no difference was apparent at the onset of ARDS. CONCLUSIONS: Multimodal therapies for ARDS were effective. Longitudinal fluctuation in PaO2/ FiO2 ratio after starting treatment appears to offer a prognostic factor for ARDS.

Continuous irrigation with gabexate mesilate around pancreaticojejunostomy after pancreaticoduodenectomy.

UNLABELLED: BACKGOUND/AIMS: The aim of this study is to present the new method of continuously irrigated around the pancreaticojejunostomy to reduce postoperative complications after pancreaticoduodenectomy. METHODOLOGY: Twenty-seven patients underwent pancreaticoduodenectomy in our institution between 2002 and 2007. Pancreaticojejunostomy was performed with the external pancreatic duct stent tube, and continuous irrigation around the pancreaticojejunostomy was started on the operative day with physiological saline solution containing gabexate mesilate. RESULTS: Mean duration of irrigation was 7.1 +/- 4.4 days, mean duration of drainage tube placement was 14.2 +/- 9 days, and mean duration of pancreatic duct drainage tube placement was 24.9 +/- 4.7 days. Pancreatic fistula was diagnosed in 8 patients. Three cases were classified as grade A and 5 cases were grade B. These pancreatic fistulae were closed by non-invasive treatment and the in-hospital death rate was 0%. CONCLUSIONS: External total drainage of the main pancreatic duct and continuous irrigation around pancreaticojejunostomy appears to avoid severe postoperative complications.

Delayed laparoscopic subtotal cholecystectomy in acute cholecystitis with severe fibrotic adhesions.

BACKGROUND: Conversion rate to open surgery is higher for patients with acute cholecystitis than in those without acute cholecystitis. We attempted to develop a laparoscopic subtotal cholecystectomy to decrease this conversion rate. METHODS: From 2000 to 2005, laparoscopic cholecystectomy for acute cholecystitis was performed in 60 patients (22 women, 38 men). Patients were divided into two groups: group A (2000 to 2002, n = 22) and group B (2003 to 2005, n = 38). When significant difficulty was encountered dissecting the gallbladder from its bed, we incised the gallbladder wall leaving the posterior wall and cauterizing the remnant mucosa (subtotal cholecystectomy, SC-1). When dissection of the gall bladder neck and triangle of Calot was difficult, the neck of the gallbladder was sutured despite clipping (SC-2). RESULTS: Mean duration from onset of symptoms to operation was 55.3 +/- 52.0 days. SC-1 was performed in 8 patients in group A and 18 patients in group B. SC-2 was performed in three patients in Group B. Conversion rate was 18.1% (4/22) in group A and 0% (0/38) in group B, compared to 0.4% (1/221) for patients without acute cholecystitis. No complications were associated with ablated gallbladder mucosa. CONCLUSION: Laparoscopic subtotal cholecystectomy offers safe and effective treatment for acute cholecystitis. The conversion rate in group B is decreased by avoiding hazardous dissection of the cystic duct.

Gut microbiota-derived D-serine protects against acute kidney injury.

Gut microbiota-derived metabolites play important roles in health and disease. D-amino acids and their L-forms are metabolites of gut microbiota with distinct functions. In this study, we show the pathophysiologic role of D-amino acids in association with gut microbiota in humans and mice with acute kidney injury (AKI). In a mouse kidney ischemia/reperfusion model, the gut microbiota protected against tubular injury. AKI-induced gut dysbiosis contributed to the altered metabolism of D-amino acids. Among the D-amino acids, only D-serine was detectable in the kidney. In injured kidneys, the activity of D-amino acid oxidase was decreased. Conversely, the activity of serine racemase was increased. The oral administration of D-serine mitigated the kidney injury in B6 mice and D-serine-depleted mice. D-serine suppressed hypoxia-induced tubular damage and promoted posthypoxic tubular cell proliferation. Finally, the D-serine levels in circulation were significantly correlated with the decrease in kidney function in AKI patients. These results demonstrate the renoprotective effects of gut-derived D-serine in AKI, shed light on the interactions between the gut microbiota and the kidney in both health and AKI, and highlight D-serine as a potential new therapeutic target and biomarker for AKI.

Evaluation of prognostic factors and scoring system in colonic perforation.

AIM: To study the significance of scoring systems assessing severity and prognostic factors in patients with colonic perforation. METHODS: A total of 26 patients (9 men, 17 women; mean age 72.7+/-11.6 years) underwent emergency operation for colorectal perforation in our institution between 1993 and 2005. Several clinical factors were measured preoperatively and 24 h postoperatively. Acute physiology and chronic health evaluation II (APACHE II), Mannheim peritonitis index (MPI) and peritonitis index of Altona (PIA II) scores were calculated preoperatively. RESULTS: Overall postoperative mortality rate was 23.1% (6 patients). Compared with survivors, non-survivors displayed low blood pressure, low serum protein and high serum creatinine preoperatively, and low blood pressure, low white blood cell count, low pH, low PaO2/FiO2, and high serum creatinine postoperatively. APACHE II score was significantly lower in survivors than in non-survivors (10.4+/-3.84 vs 19.3+/-2.87, P=0.00003). Non-survivors tended to display high MPI score and low PIA II score, but no significant difference was identified. CONCLUSION: Pre- and postoperative blood pressure and serum creatinine level appear related to prognosis of colonic perforation. APACHE II score is most associated with prognosis and scores>or=20 are associated with significantly increased mortality rate.

[A case of non-small cell lung cancer accompanied with hemorrhage after chemotherapy including gemcitabine].

A 51-year-old man underwent left upper lobectomy due to pulmonary adenocarcinoma (cT2N1M0, stage IIB) in August, 2003. Since he turned out pT2N3M0 stage IIIB, he received combination chemotherapy with carboplatin and gemcitabine. During a second course chemotherapy, he was admitted again because of dyspnea and the deterioration of diffuse interstitial shadows in both lungs. He was treated with various antibiotics and corticosteroids. Unfortunately, he could not recover. An autopsy was performed. Microscopic features of the lung revealed diffuse alveolar damage and pulmonary hemorrhage. In this case, pulmonary hemorrhage should be considered as a complication of gemcitabine-induced lung injury.

Successful closure of spontaneous esophageal rupture (Boerhaave's syndrome) by endoscopic ligation with snare loops.

INTRODUCTION: Spontaneous esophageal rupture is a rare condition with a high mortality rate, and it is generally treated by surgery. In the present report, successful non-surgical closure of spontaneous esophageal rupture by endoscopic ligation with snare loops in a patient with pyopneumothorax and septicemia is presented. CASE DESCRIPTION: The case of an 80-year-old man patient with spontaneous esophageal rupture who was cured by endoscopic ligation with snare loops is reported. The patient was admitted with severe chest pain. Chest CT scan revealed pneumomediastinum, and an upper gastrointestinal series using gastrografin showed leakage of contrast medium from the lower esophagus. Therefore, a diagnosis of spontaneous esophageal rupture to the thorax was made. Since the family refused surgery, the patient was treated conservatively. Since extensive blood in the stool was noted on day 5, an emergency endoscopic examination was performed. Clipping was performed around the perforation, and the clips were ligated with snare loops. The patient was discharged on day 83 without recurrence. DISCUSSION AND EVALUATION: We suggest that endoscopic ligation with snare loops should be chosen for elderly people and high-risk cases.

Vasodilator signals from the ischemic myocardium are transduced to the coronary vascular wall by pertussis toxin-sensitive G proteins: a new experimental method for the analysis of the interaction between the myocardium and coronary vessels.

OBJECTIVES: We sought to detect cross-talk between the beating heart and coronary vascular bed during myocardial ischemia and to test the hypothesis that the cross-talk is mediated by pertussis toxin (PTX)-sensitive G proteins (G(PTX)) in vessels. BACKGROUND: Coronary flow is closely related to the myocardial metabolic state, indicating the existence of a close interaction between cardiac muscle and coronary vascular beds. Experimental methods for the analysis of the interaction, however, have not been established. METHODS: Coronary detector vessels (DVs) were isolated from rabbit hearts. One end of the vessel was cannulated to a micropipette, and the other end was ligated. After the DV was pressurized (60 cm H(2)O), it was gently placed on the myocardium, which was perfused by the left anterior descending coronary artery (LAD) of anesthetized, open-chest dogs (n = 23). The LAD was occluded, and the DV diameter was observed using an intravital microscope with a floating objective system. To evaluate the involvement of G(PTX), the DV was pre-incubated with PTX (100 ng/ml). RESULTS: The LAD occlusion of the beating heart produced significant dilation of DVs (241 +/- 25 microm) by 10%. The DVs pretreated with PTX (250 +/- 27 microm) did not dilate in response to myocardial ischemia. N(omega)-nitro-L-arginine (100 micromol/l), but not glibenclamide (5 micromol/l), abolished the ischemia-induced DV dilation. CONCLUSIONS: We have established experimental methods for direct analysis of the interaction between the myocardium and coronary microvessels. We conclude that the ischemic myocardium releases transferable vasodilator signals that are transduced by means of the G(PTX) located in the vascular walls. The nitric oxide pathway is involved in the signal transduction.

Hypercholesterolemia impairs transduction of vasodilator signals derived from ischemic myocardium: myocardium-microvessel cross-talk.

OBJECTIVE: Coronary microvessels are functionally coupled to the myocardial metabolic state. In hypercholesterolemia, the coronary vascular dysfunction extends to microvascular levels. We hypothesized that the vasodilator signal transduction from ischemic heart is impaired in the coronary microvascular wall of hypercholesterolemia. METHODS AND RESULTS: Rabbits were fed with normal chow (control group) or 2% high-cholesterol diet (hypercholesterolemia group) for 8 weeks. Coronary microvessels isolated from rabbit hearts were pressurized and gently placed on a beating canine heart. Myocardial ischemia was produced in the beating heart and the diameter of the isolated microvessel was observed using an intravital microscope with a floating objective. In control group, the isolated microvessels significantly dilated 2 minutes after the onset of ischemia, and a plateau was observed at 10 minutes. In contrast, the microvessels from hypercholesterolemia group did not dilate during ischemia. Dihydroethidium fluorescence microscopy revealed an elevated superoxide level in the microvessels of hypercholesterolemia group. The application of tiron (free radical scavenger) significantly dilated the isolated microvessels only from hypercholesterolemic animals. CONCLUSIONS: We conclude that the transduction of vasodilator signals derived from ischemic myocardium is impaired in the coronary microvascular wall of hypercholesterolemia. Enhanced oxidative stress in hypercholesterolemia may alter the microvascular function.

Fabrication and Characterization of Electronic and Optical Properties of Polyaniline Nanopatterns.

The authors conducted polyaniline (HA) polymerization on a micro-scale patterned Si water and nano-scale patterned Al surface. Polymerization was performed using a microliter solution droplet made of aniline, HCI and oxidation agent ammonium peroxodisulfate (APS). The droplet was dropped on a flat Si wafer, a micro-patterned Si wafer and a nanostructured Al surface. The SEM image showed that PA was densely polymerized on the circle edge of the dropped 1 mm sized droplet on the flat Si wafer because of large surface tension due to the flat surface. On the other hand, a droplet was broken on a circular trench pattern of 100 µm in diameter fabricated on a Si wafer. The width and depth of the trench were 1 µm and 1 µm, respectively. Tree-like polymer was intensively polymerized along the circular trench. Droplet was also dropped on a lattice trench pattern whose pitch was 10 µm. The width and the depth of the trench were 1 µm and 1 µm, respectively. The SEM image showed that dots of PA were fabricated along the trenches. Far smaller dots of PA were also observed on the flat area of the lattice. Thus, micro-scale structure affects the shape and size of PA in polymerization. Nanoscopic polymerization of PA was conducted locally in a nanoscale highly-oriented line pattern with nanoscale trenches formed on an Al surface. One of the characteristic fabricated patterns was a highly conductive PA line pattern whose pitch was 100 nm. In this case, point-contact IV characteristic measurement, step-like curve was observed. PL spectra of the PA line-pattern exhibited significantly enhanced emission peaks at 380, 450 anc 550 nm due to PA which were overlapped by the rippled PL pattern due to the Al nanostructure.

Multiple esophagogastric granular cell tumors.

Multiple granular cell tumors of the esophagus and the stomach found in a 53-year-old man are reported. One lesion was detected within the lower thoracic esophagus and seven lesions were detected in the stomach. The esophageal tumor was resected endoscopically, and gastrectomy was performed for the multiple gastric lesions. Histologically, the tumors consisted of spindle or polyhedral cells and the cytoplasm contained punctated eosinophilic granules with positive immunohistochemical staining for S-100 protein. The tumors were mainly located in the submucosal layer. Some tumor cells were seen in the mucosae propria and the muscularis propria. The tumor cells were only slightly positive for p53- and Ki-67-immunohistochemical stainings. Based on these findings, we diagnosed the granular cell tumors as benign. Granular cell tumor is comparatively rare in clinical practice, but a few such tumors have been seen in the digestive tract. A few cases of multiple esophagogastric granular cell tumors have also been reported in the literature.

[Stent-assisted percutaneous transluminal angioplasty for intracranial vertebral and basilar artery stenosis: two case reports].

We report two cases of patients who underwent stent-assisted percutaneous transluminal angioplasty for intracranial vertebral artery (VA) and basilar artery (BA) stenosis. They presented with sudden onset of vertigo and right hemiparesis. Vertebral angiographies revealed severe proximal BA stenosis (case 1) and intracranial VA stenosis (case 2). They underwent angioplasty and stenting, with excellent angiographic results. The availability of new flexible intravascular stents, allowing access to tortuous proximal intracranial vessels, provides a new therapeutic approach for patients with vertebral and basilar artery stenosis.

[Anesthetic management for a patient with Charcot-Marie-Tooth disease using propofol and nitrous oxide].

A 65-year-old woman who had been diagnosed as having Charcot-Marie-Tooth disease (CMTD) 8 years ago and was scheduled to undergo excision of a spinal tumor in the prone position. General anesthesia using propofol was selected as the anesthetic method in order to avoid possible occurrence of malignant hyperthermia due to inhalation anesthetics. The patient was given 80 mg of propofol for anesthetic induction, and then propofol was infused at a rate of 4-5 mg.kg-1.h-1 with intermittent administration of fentanyl (total dose of 0.25 mg) for anesthetic maintenance. Vecuronium 4 mg was injected for intratracheal intubation, and then vecuronium 1 mg was injected at 50 min intervals. The operation proceeded uneventfully. The necessary time for anesthesia was over 460 minutes. There was no delay in wakening, and the patient experienced no problems in the postoperative course. Intravenous anesthesia using propofol is thought to be a safe and effective method of anesthesia for patients with CMTD.

[A patient with metastatic gastrointestinal stromal tumor who responded to STI571].

We report a case of gastrointestinal stromal tumor (GIST) with multiple hepatic metastases that responded to tyrosine kinase inhibitor STI571. A 30-year-old woman underwent total gastrectomy on July 10, 1998, with a diagnosis of submucosal tumor of the stomach. Pathological analysis of the primary lesion revealed strong expression of c-kit, and it was diagnosed as GIST. The patient underwent tumor excision due to peritoneal recurrence on May 1, 2000 and November 13, 2000. On August 8, 2001, multiple liver metastases were detected by abdominal CAT scan. Treatment with STI571 at a dose of 400 mg/day for 28 days was initiated on September 14, 2000. CAT scan showed rapid tumor shrinkage after 3 weeks of treatment (reduction rate of 56%) and the response continued after 7 weeks of treatment (reduction rate of 71%). Thus, we evaluated the response as PR. Leukocytopenia, edema, diarrhea and nausea were observed; however, all toxicities were mild and tolerable. This case suggests the efficacy of STI571 for metastatic GIST.

[Preparation of pamphlets to teach the technique of home parenteral nutrition aiming at timely back home].

The home drip infusion is a stressful procedure for both patients and families under HPN at home. Effective and reliable guidance for drip infusion management should be provided while patients are still at the hospital to realize reliable home care. We revised the HPN Guidance Manual and report the process in this article. We revised the manual according to the principles that "the guidance is subdivided into 3 steps so that the contents of the guidance can be adjusted for individual patients", that "a lot of photos and illustrations for frequently used 2 models are placed" and that "a video is prepared to make the most of the impact motion pictures can give". We want to use the manual in future clinical practices.