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Contains fulltext : 249977.pdf (Publisher’s version ) (Closed access) BACKGROUND: It is important to evaluate whether a new treatment for heart failure with reduced ejection fraction (HFrEF) provides additive benefit to background foundational treatments. As such, we aimed to evaluate the efficacy and safety of empagliflozin in patients with HFrEF in addition to baseline treatment with specific doses and combinations of disease-modifying therapies. METHODS: We performed a post-hoc analysis of the EMPEROR-Reduced randomised, double-blind, parallel-group trial, which took place in 520 centres (hospitals and medical clinics) in 20 countries in Asia, Australia, Europe, North America, and South America. Patients with New York Heart Association (NYHA) classification II-IV with an ejection fraction of 40% or less were randomly assigned (1:1) to receive the addition of either oral empagliflozin 10 mg per day or placebo to background therapy. The primary composite outcome was cardiovascular death and heart failure hospitalisation; the secondary outcome was total heart failure hospital admissions. An extended composite outcome consisted of inpatient and outpatient HFrEF events was also evaluated. Outcomes were analysed according to background use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs) or angiotensin receptor neprilysin inhibitors (ARNIs), as well as β blockers and mineralocorticoid receptor antagonists (MRAs) at less than 50% or 50% or more of target doses and in various combinations. This study is registered with ClinicalTrials.gov, NCT03057977. FINDINGS: In this post-hoc analysis of 3730 patients (mean age 66·8 years [SD 11·0], 893 [23·9%] women; 1863 [49·9%] in the empagliflozin group, 1867 [50·1%] in the placebo group) assessed between March 6, 2017, and May 28, 2020, empagliflozin reduced the risk of the primary outcome (361 in 1863 participants in the empagliflozin group and 462 of 1867 in the placebo group; HR 0·75 [95% CI 0·65-0·86]) regardless of background therapy or its target doses for ACE inhibitors or ARBs at doses of less than 50% of the target dose (HR 0·85 [0·69-1·06]) and for doses of 50% or more of the target dose (HR 0·67 [0·52-0·88]; p(interaction)=0·18). A similar result was seen for β blockers at doses of less than 50% of the target dose (HR 0·66 [0·54-0·80]) and for doses of 50% or more of the target dose (HR 0·81 [0·66-1·00]; p(interaction)=0·15). Empagliflozin also reduced the risk of the primary outcome irrespective of background use of triple therapy with an ACE inhibitor, ARB, or ARNI plus β blocker plus MRA (given combination HR 0·73 [0·61-0·88]; not given combination HR 0·76 [0·62-0·94]; p(interaction)=0·77). Similar patterns of benefit were observed for the secondary and extended composite outcomes. Empagliflozin was well tolerated and rates of hypotension, symptomatic hypotension, and hyperkalaemia were similar across all subgroups. INTERPRETATION: Empagliflozin reduced serious heart failure outcomes across doses and combinations of disease-modifying therapies for HFrEF. Clinically, these data suggest that empagliflozin might be considered as a foundational therapy in patients with HFrEF regardless of their existing background therapy. FUNDING: Boehringer Ingelheim and Eli Lilly and Company.

A cross-sectional study. Neuropathic pain (NP) after spinal cord injury (SCI) tends to be hard to treat, and its heterogeneous properties make it difficult to identify and characterize. This study was conducted to assess the characteristics of SCI-related NP in detail. A single hospital for SCI rehabilitation. This study included 72 patients who were seen at our hospital in 2012 and 2013 and who had sustained SCI at least 3 months before enrollment. The patients completed the Neuropathic Pain Symptom Inventory (NPSI) and the Short Form (SF)-36 Health Inventory. The NPSI score was analyzed for correlations with clinical presentations of SCI and SF-36 subitems. Paresthesia/dysesthesia was the most common subtype of NP after SCI. With regard to location, below-level superficial NP was significantly more intense than at-level pain. Patients who underwent surgery showed significantly less evoked pain compared with patients with non-surgery. Patients reported significantly more severe pain if >1 year had elapsed after the SCI. Patients with an American Spinal Injury Association Impairment Scale grade of B for completeness of injury reported more intense NP than those with other grades. Among the SF-36 subitems, NP correlated significantly with bodily pain, general health and mental health. NP in SCI patients was significantly associated with the location of pain, the time period since the injury, surgery and quality-of-life factors. A more detailed understanding of the characteristics of NP may contribute to better strategies for relieving the pain associated with SCI.

The palisade vessels present at the distal end of the esophagus are considered to be a landmark of the esophagogastric junction and indispensable for diagnosis of columnar-lined esophagus on the basis of the Japanese criteria. Here we clarified the features of normal palisade vessels at the esophagogastric junction using magnifying endoscopy. We prospectively studied palisade vessels in 15 patients undergoing upper gastrointestinal endoscopy using a GIF-H260Z instrument (Olympus Medical Systems Co., Tokyo, Japan). All views of the palisade vessels were obtained at the maximum magnification power in the narrow band imaging mode. We divided the area in which palisade vessels were present into three sections: the area from the squamocolumnar junction (SCJ) to about 1 cm orad within the esophagus (Section 1); the area between sections 1 and 3 (Section 2); and the area from the upper limit of the palisade vessels to about 1 cm distal within the esophagus (Section 3). In each section, we analyzed the vessel density, caliber of the palisade vessels, and their branching pattern. The vessel density in Sections 1, 2, and 3 was 9.1 ± 2.1, 8.0 ± 2.6, and 3.3 ± 1.3 per high-power field (mean ± standard deviation [SD]), respectively, and the differences were significant between Sections 1 and 2 (P= 0.0086) and between Sections 2 and 3 (P0.0001). The palisade vessel caliber in Sections 1, 2, and 3 was 127.6 ± 52.4 µm, 149.6 ± 58.6 µm, and 199.5 ± 75.1 µm (mean ± SD), respectively, and the differences between Sections 1 and 2, and between Sections 2 and 3, were significant (P0.0001). With regard to branching form, the frequency of branching was highest in Section 1, and the 'normal Y' shape was observed more frequently than in Sections 2 and 3. Toward the oral side, the frequency of branching diminished, and the frequency of the 'upside down Y' shape increased. The differences in branching form were significant among the three sections (P0.0001). These results indicate that the density of palisade vessels is highest near the SCJ, and that towards their upper limit they gradually become more confluent and show an increase of thickness. Within a limited area near the SCJ, observations of branching form suggest that palisade vessels merge abruptly on the distal side. We have demonstrated that palisade vessels are a useful marker for endoscopic recognition of the lower esophagus.

There are many suicide-attempted patients admitted to the critical care medical center of the Kitakyushu General Hospital. Suicide-attempted patients need psychosocial intervention from the beginning of their hospitalization, because they have their own psychosocial problems. Accordingly, medical social workers (MSW) give psychosocial assistance to the patients in our critical care medical center. In 1997, we participated in the treatment of 53 patients out of 64 suicide-attempted patients. Forty-four patients committed suicide by ingesting some drugs or poisons, and 9 patients committed suicide by jumping from a height or by self-burning. Kinds of drugs or chemicals used for suicide were medicinal drugs (55.3%), household medicines (14.9%), agricultural chemicals (10.7%), insecticides (8.5%), detergents (4.3%), household chemicals (4.3%) and others (2.0%). The largest number of male patients was in their fifties (6 out of 15 male patients). Patients with alcoholism held the first place in male patients. The largest number of female patients was in their twenties (11 out of 29 female patients). There were many female patients with mood disorder, drug dependence or psychopathy. If the patients are discharged without receiving psychosocial measures, it may be every possibility that the patients commit suicide again. MSW make the cause of suicide clear and assess the mental status, and also have interview with patient's families. If both MSW and the doctors in charge judge that there is high possibility of repeated suicide, MSW introduce the patient to the special hospital under the consent of the patient and families. Thirty-five patients out of 44 patients transferred to the psychiatric hospitals. It is important that MSW join the treatment of suicide-attempted patients in order to prevent repeated suicide.

Fiberoptic colonoscopy has been a routine therapeutic modality for colorectal polyps in pediatric patients. Methods of bowel preparation, anesthesia, area of investigation and treatment depending on histopathology are still controversial. In order to clarify the rationale of pediatric colonoscopy the present study was performed.We analyzed the results of colonoscopic examination in 21 patients with colorectal polyps. Mean patient age was 3.7 years, with a range of 1--7 years. Rectal polyps were seen in 10 cases: seven had a solitary polyp (juvenile in six and adenoma in one) and three had multiple polyps (juvenile, lymphoid and Peutz--Jeghers coexisting with hyperplastic polyps). Sigmoid colon polyps were seen in 10 cases: all were solitary juvenile polyps, but one had adenomatous change. Another had multiple Peutz-- Jeghers polyps located in the entire colon. Flexible colonoscopic polypectomy was performed in 16 patients and transanal polypectomy was performed in four patients. Autoamputation was seen in two cases of juvenile polyp (resection was ultimately performed in a case having repeated autoamputation). After removing the polyps, all patients have had no recurrence for a period ranging from 6 months to 15 years, except for one case with Peutz--Jeghers syndrome.Most polyps are located in the rectum or the sigmoid colon. Although the majority are solitary or juvenile polyps, because histopathologic variety is seen in pediatric colon polyps, histopathologic examination of each polyp is important to detect any dysplastic or adenomatous element with malignant potential and to make a suitable follow-up schedule. Symptomatic polyps should be removed by fiberoptic colonoscopy or transanal resection with total colon endoscopic examination under general anesthesia. Polypectomy using the electrocautery snare and clip is effective and safe and bowel preparation using polyethylene glycol electrolyte solution is sufficient for the procedure.

Activated immediate early genes (IEGs) play key roles in mediating cellular response after ischemia/reperfusion (I/R) injuries in some organs such as liver, heart and kidney. However, there is no report investigating an association between the activation of IEGs and cellular regeneration or programmed cell death after I/R in small intestine.We examined a sequential expression of c-fos and c-jun after I/R in rat small intestine using reverse transcription-polymerase chain reaction and Northern blot analysis, and compared the patterns with coexistent two parameters: (1) regeneration determined by immunohistochemical detection of proliferating cell nuclear antigen, (2) programmed cell death determined with the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end-labeling (TUNEL) method and DNA fragmentation.The expression of c-fos and c-jun mRNA increased markedly 15 min after reperfusion and was, respectively, 6.3 and 4.4 times higher than in controls. Proliferating cell nuclear antigen expression was significantly elevated between 5 min and 4 hr, peaking at 30 min after reperfusion. Apoptosis showed a peak 60 min after reperfusion. Apoptosis after I/R was detected in the nuclei of absorptive epithelial cells by the TUNEL method, and these apoptotic signals were consistent with the expression of c-Fos and c-Jun proteins using an immunohistochemical method.These results suggest that overexpression of c-fos and c-jun after I/R in the small intestine correlates with programmed cell death and subsequent cellular regeneration.

Recent studies have demonstrated that human neuroblastoma (NB) cell lines have at least two morphological appearance of neuroblastic (N-type) and substrate-adhesive (S-type) cells. Our previous study revealed that S-type cells expressed alpha-smooth muscle actin and/or desmin, suggesting the smooth muscle cell characteristics of S-type cells. In the present study, a new human NB cell line, KP-N-YS, was established from bone marrow metastasis of a four-year-old boy with advanced NB, originating from the left adrenal gland. Subsequently N-type cell clone (YS1n) and S-type cell clone (YS2s) was isolated from the parent cell line. Parent and clones cell lines were identified as NB by surface membrane antigen and cytoskeletal protein analysis, and these cell lines were demonstrated as common progenitors by chromosomal analysis. Furthermore the presence of basic calponin were determined by indirect immunofluorescence, Western blot, as well as by RT-PCR (reverse transcriptase-polymerase chain reaction). Our demonstration of basic calponin not in N-type cells, but in S-type cells supports the plausible smooth muscle cell characteristics of this NB cell line.

The purpose of our study was to identify risk factors for low birthweight (LBW; birthweight2500 g) in Japanese infants. The data was collected from questionnaires completed by the parents of 23132 infants who underwent a standardized well baby check-up for 1-month-old infants, conducted by the Fukuoka City Medical Association from 1987 to 1995. The following eight factors and their second-order interaction terms were examined as potential risk factors for LBW: maternal age at delivery, history of live-born LBW infant, history of abortion in previous pregnancies, maternal smoking, coffee and alcohol consumption during pregnancy, prenatal training and live birth order. The results of multiple logistic regression analysis showed that the following three factors and one interaction term significantly contributed to LBW: history of live born LBW infant, maternal smoking, live birth order and the interaction between maternal smoking and live birth order. The smoker-related risk for LBW was quite different in each of the three groups stratified by live birth order. Efforts should be made, for example, to increase the accessibility of early, high-quality prenatal care for the high-risk groups with previous LBW babies and to implement smoking intervention, ranging from specific medical procedures to broad-scale public health and health-related educational programs in schools.

Long-term survivors (or = 5 years) of pancreatoduodenal carcinoma were evaluated. The absence of retropancreatic invasion seemed to be an important factor for long-term survival in carcinoma of the pancreatic head, carcinoma of the intrapancretic bile duct confined within the bile duct wall, and stage II papilla of Vater carcinoma. The mode of infiltration was INF alpha or INF beta, with a low infiltration tendency. Lymph node metastasis, when present, was confined to the pancreatic head. It is noteworthy that two of the patients with intrapancreatic bile duct cancer had perineural infiltration to the pancreatic head plexus. In patients treated by extended resection, postoperative malnutrition and diarrhea was severe, indicating the importance of long-term nutritional management.

It has been suggested that the number of argyrophilic nucleolar organizer regions (AgNORs) correlates with cellular activity and the aggressiveness of malignancy. The mean number of AgNORs per nucleus may, therefore, be a prognostic factor for hepatocellular carcinoma (HCC). The purpose of this study was to evaluate the prognostic significance of the number of AgNORs in HCC. The silver-staining technique was applied to surgically resected specimens to indicate AgNORs. Eighty-nine of the specimens were of HCC, 23 were of normal liver adjacent to HCC, and 32 were of cirrhotic liver adjacent to HCC. The number of AgNORs of HCC (mean +/- SD, 3.26 +/- 1.23) was significantly higher than those of normal liver (1.37 +/- 0.13) and cirrhotic liver (1.49 +/- 0.14). The number of AgNORs was significantly correlated with serum alpha-fetoprotein level, tumor size, portal vein invasion, and Edmondson-Steiner histological grade. In patients undergoing curative resection, the survival rate of those with a high number (3.04) of AgNORs was significantly worse than that of those with a low number (or = 3.04) of AgNORs. Multivariate analysis showed that the number of AgNORs was a significant prognostic indicator in patients without portal vein invasion, and portal vein invasion was the only significant variable when all patients undergoing curative resection were assessed together. The results of this study suggest that the number of AgNORs is useful as an indicator of the grade of malignancy and as a predictor of the prognosis of patients with HCC who do not have portal vein involvement.

A study was designed to determine whether oesophageal carcinomas can be induced through reflux of duodenal contents. Male Wistar rats weighing 230-250 g were divided into three groups according to the surgical procedure performed: (1) the duodenal contents were directed into the forestomach through a stoma (duodeno-forestomach reflux); (2) the duodenal contents were regurgitated into the forestomach through the glandular stomach (duodeno-glandular-forestomach reflux); and (3) a sham operation was performed as a control. Animals were fed standard CRF-1 solid food and tap water that was not exposed to carcinogens and were sacrificed 50 weeks post-operatively. While no neoplasia was observed in any of the 32 control rats, 4/11 (36%) with duodeno-forestomach reflux and 3/18 (17%) animals with duodeno-glandular-forestomach reflux developed carcinomas in the lower oesophagus and forestomach. The incidence in each group was significantly higher than in the controls (P < 0.01 and P < 0.05 respectively). Six of the seven lesions consisted of squamous cell carcinomas, and one was a mucinous adenocarcinoma. Oesophageal columnar epithelial metaplasia was observed in two (18%) of the animals with duodeno-forestomach reflux. Carcinomas were always surrounded by chronic inflammatory changes, including regenerative thickening, basal cell hyperplasia and dysplasia. Additional well-differentiated adenocarcinomas were observed in the prepyloric antrum of 6/18 (33%) animals with duodeno-glandular-forestomach reflux. These findings indicate that chronic reflux of duodenal contents may cause oesophageal carcinoma. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6

The benefits of a school-based fluoride mouth rinsing in a community dental health program were evaluated. In village "M", children from 4 to 14 years old have been participating in a school-based fluoride mouth rinsing program since 1974. In addition, an informal association for dental health of children was inaugurated in 1975 to support the community dental health program. In village "K", there were no fluoride mouth rinsing programs. However, the usual dental health education conducted in all schools was similar in both communities. In order to compare these two communities, dental examinations were carried out in 1990. The total number of subjects from 6 to 14 years old was 331 in village "M" and 408 in village "K". In village "M" for longitudinal comparison, 12-year-olds, 1,054 in total, were examined annually from 1974 to 1990. The DMFT-index in all subjects in village "M" was 76.1% lower than in village "K". In village "M", the DMFT-index in 1990 decreased 79.0% compared to 1974. The economic benefits obtained through the caries reduction were evaluated. In 1990 the mean cost of dental treatment for subjects 14 years old was 27,840 yen per person in village "K" and 4,248 yen in village "M". The cost-benefit ratio was 18.8 and the cost-effectiveness ratio was 137 yen. These remarkable benefits from the prevention of dental caries appears to have been mainly obtained due to the participation of children aged 4 to 14 years old in a school-based fluoride mouth rinsing program.

According to previous reports, branched chain ketoacids (BCKAs) are undetectable in liver and brain. A procedure is described for HPLC analysis of tissue concentrations of BCKA that achieves 80% recovery of labeled 2-ketoisocaproate (KIC) added to frozen powdered liver. In normal overnight-fasted rats, substantial hepatic uptake was demonstrable in the order KIC2-ketoisovalerate (KIV) congruent to 2-keto-3-methylvalerate (KMV). All three BCKAs were very low in freeze-clamped liver. Liver concentrations were only 15% to 22% of the mean of portal vein, hepatic vein, and hepatic artery (aorta) concentrations. In view of the probable contribution to total liver content of extracellular BCKAs, the intracellular concentrations in liver tissue must be vanishingly low. Somewhat higher amounts were present in freeze-clamped kidney and heart tissue, and significant uptake of KIC and KMV by kidney was found. Brain released KIC. Muscle contained concentrations of BCKA that were 35% to 72% of concentrations in plasma, and it released all three BCKAs. Similar results were obtained from tissues in overnight-fasted dogs, except that even lower levels were found in freeze-clamped brain (sampled before circulation ceased) than were found in the liver. Plasma levels in dogs were similar to those of rats. In both species the tissue-to-plasma ratios were higher for KIV than for KMV or KIC. Remarkably low BCKA levels in liver and brain are unexplained, particularly in light of evidence that BCKAs gain access to cells in both organs.

One hundred and thirty-two patients with hepatocellular carcinoma in stages III and IV were studied. Seventy-six patients who underwent hepatectomy were divided into three groups: relative curative resection (RC: n = 30), relative noncurative resection (RNC: n = 30) and absolute noncurative resection (ANC: n = 16). Fifty-six patients were treated by non surgical procedures such as hepatic arterial infusion, transcatheter arterial embolization, ethanol injection and hyperthermia. The cumulative survival rate of hepatectomy patients was significantly better than that of non-surgically treated patients. The most significant prognostic factor was the presence of the portal venous invasion. In the patients without tumor thrombi or with tumor thrombi found microscopically, the cumulative survival rates of both RC and RNC were significantly better than those of ANC and non-surgically treated patients, but in the patients with tumor thrombi found grossly, there was no difference between hepatectomy patients and non-surgically treated patients. These results indicate that surgical treatment for advanced hepatocellular carcinoma improve the prognosis of the patients without tumor thrombi found grossly.

An aim of the present study is to clarify the changes of esophageal function after surgical treatments of the esophageal varices or the congenital esophageal stenosis in children. Esophageal manometric studies were performed in sixteen children undergoing the esophageal transection with paraesophageal devascularization or the esophago-esophagostomy with partial esophagectomy before, within 1 month and over 7 months after the operation. The pressure of lower esophageal sphincter (LES), the length of LES, the LES relaxation test and the gastroesophageal reflux (GER) inducing test were measured. 1) Esophageal transection; The pressure dropped within 1 month and returned to the preoperative level over 11 months after the operation. Temporal deterioration of LES function was observed during the early postoperative days. However, return to the preoperative state was gained over 1 year. 2) Esophago-esophagostomy; The pressure and the length of LES were not changed after the operation. The LES function was disturbed preoperatively and moreover long postoperatively, in the case when congenital stenosis closely existed to the esophago-gastric junction. Degree of the postoperative disturbance of the LES function may be influenced by the distance to the part of the transection or the partial esophagectomy from the E-C junction.

In rats receiving total parenteral nutrition with or without sodium 2-ketoisocaproate (KIC; 2.48 g.kg-1.day-1), L-(1-{sup 13}C)leucine and (1-{sup 14}C)KIC were constantly infused for 6 h. CO{sub 2} production, {sup 14}CO{sub 2} production, {sup 13}CO{sub 2} enrichment, urinary urea nitrogen (N) plus ammonia N and total urinary N were measured. Whole body protein synthesis (S) was calculated in non-KIC-infused rats and also in unfed rats infused with (1-{sup 14}C)leucine from fractional oxidation of labeled leucine (1-F), where F is fractional utilization for protein synthesis, and urea N plus ammonia N excretion (C) as S = C x F/(1-F). Addition of KIC caused a significant reduction in N excretion and a significant improvement in N balance. Fractional oxidation of labeled KIC increased, whereas fractional utilization of labeled KIC for protein synthesis decreased, but the extent of incorporation of infused KIC into newly synthesized protein (as leucine) amounted to at least 40% of the total rate of leucine incorporation into newly synthesized whole body protein. We conclude that addition of KIC spares N in parenterally fed rats and becomes a major source of leucine for protein synthesis.

In rats infused with NaH14CO3, 14CO2 exhalation approached an asymptotic rate equal to 96.0 +/- 1.3 (SD) % of the infusion rate of 14C in a monoexponential manner with a half-time of 20 min. In rats infused with [1-14C]leucine, 14CO2 exhalation (/0.96) approached an asymptotic value, (1-F), of 16-25% of 14C infusion rate (mean 20.4%) in a monoexponential manner with a half-time of approximately 31 min. Whole body protein synthesis (S) was calculated from 1-F and urea N plus ammonia N excretion (C) as S = CF/(1-F). S was a uniform function of body weight in these rats, in six additional rats in which S was measured 6 h after single intravenous injection of [1-14C]leucine and also in previously reported rats given single injections. The relationship was S (mg.100 g-1.h-1) = 11-0.143 body wt (g) +/- 8.3. In six of these rats, S was also estimated from the plateau specific activity of plasma leucine or plasma 2-ketoisocaproate (KIC); the former estimate of S was significantly lower (by an average of 17%), but S was the same when specific activity of KIC was employed. These results support the validity of the expired 14CO2 technique for measuring S.

Two cases of condyloma acuminatum of the male urethra were clearly demonstrated by retrograde urethrogram and endoscopy. Characteristic urethrographic and endoscopic appearances of these cases are presented.

Between 1961 and 1983, eighty-six patients with intrahepatic gall stones were identified from a group of 1,140 patients admitted for cholelithiasis. Surgical procedures performed in this series were 37 choledochotomies with external biliary drainages, 33 transduodenal papilloplasties, 37 bilioenteric anastomosis and 15 hepatectomies. In the long term follow up studies after surgical treatment by each procedures, the favorite results were obtained in 41.2% of cases with choledochotomies with external drainages, in 34.4% of cases with transduodenal papilloplasties, in 82.4% of cases with bilioenteric anastomosis and in 88.7% of cases with hepatectomies. Hepatectomy seemed to be a most effective treatment for the prevention of recurrence of stones. However, if the calculi were in the right or both of hepatic lobes, hepatectomy might be a high risk operation and technical proficiency were required in operation. In such cases, we performed an end to side anastomosis between the common hepatic duct and the jejunum (Roux en Y anastomosis) for the postoperative endoscopic lithotomy. In this operation the jejunal stump was made to be an enterocutaneous fistula for the later percutaneous endoscopic lithotomy. This operation has the following advantages; 1) the time of operation were shortened in the removal of stones because of this operation were performed for the postoperative endoscopic lithotomy, 2) retrograde cholangitis was less likely to develop than other operations, 3) retained stones dropped into bowel easily by making a big anastomotic stoma, 4) the cholangioscope could be inserted into either bile ducts of the right and left hepatic lobes, 5) the fistula would be able to be reused for the endoscopic treatment at later recurrence of intrahepatic gall stones.

This is a rare case of a 57-year-old-male patient with familial, benign and multiple pheochromocytoma recurring 23 years after initial surgery. His 131I-MIBG scintigraphy was false negative, but his son's 131I-MIBG scintigraphy was true positive.

A phase II evaluation of UFT, a mixture of tegafur and uracil, was performed in 13 patients with non-small cell lung cancer (eight patients with adenocarcinoma and five patients with squamous cell carcinoma). UFT at a dose of 600 mg was given per os every day for more than four weeks. Among 12 evaluable patients, one patient with adenocarcinoma of the lung showed partial response. The response rate for UFT was 8.3%. Toxic effects included anorexia (31%), nausea (15%), liver disorder (15%), and pigmentation (8%).

A 64-year-old man with the chief complaint of abdominal fullness was hospitalized on the suspicion of pancreatic tumor. The tumor was thought to be a pancreatic or retroperitoneal tumor, based on examinations of ultrasonography and CT scan of the upper abdomen, angiography of abdominal arteries, and ERCP. Laparotomy revealed that the tumor was inoperable inflammatory fibrous histiocytoma. Combined anti-cancer chemotherapy with doxorubicin, cyclophosphamide, and vincristine induced partial response. The duration of response was six months, and the patient died of tumor growth 18 months after the initial diagnosis.

We have investigated a method of intraoperative monitoring of anesthetic depth using the electroretinogram (ERG). The effects of enflurane on ERG were studied in 12 patients undergoing surgical procedures. Recordings were made at 0%, 0.8%, 1.7% end-tidal enflurane concentrations. There were statistically significant increases in the latencies of the a-waves, b-waves and oscillatory potentials (OP) with increasing concentrations of enflurane. The amplitudes of the a-waves were reduced with increasing concentrations of enflurane, but the amplitudes of the b-waves did not change. The latencies of OP were thought to be the most sensitive indicator of the anesthetic depth among these parameters. To apply this technique to clinical practice, there were many problems to be solved. However, this may be one of useful monitors of anesthetic depth in future.

A 56-year-old man was admitted to our hospital with complaints of dyspnea and right pleural effusion. Malignant pleural mesothelioma was diagnosed, based on the high level of hyaluronic acid in the pleural fluid and manifestation of malignant cells by pleural needle biopsy. Anticancer chemotherapy with cisplatin and intrapleural injections of adriamycin against this mesothelioma was carried out because of the presence of stage III by Butchart's classification. Regression of the tumor, decrease of pleural fluid and decrease of LDH level in effusions were observed after this chemotherapy. Cisplatin was easily transported into the pleural fluid, and its concentration was maintained for a satisfactorily long period.

Restriction endonuclease mapping of the beta-globin genomic region was used for studying the molecular basis of two variants of hereditary persistence of fetal hemoglobin (HPFH): an African G gamma (beta)+ HPFH and a Chinese HPFH variant with predominant synthesis of A gamma chains. HPFH and control DNA samples were digested with a battery of restriction enzymes, and the fragments were identified by hybridization to a family of discrete probes. DNA fragments from the A gamma HPFH (Chinese) and the G gamma (beta)+ HPFH individuals were identical with those of the normal controls. These findings suggest that the two mutants are the result of small structural anomalies of DNA sequences that play a role in the regulation of the expression of gamma-globin genes.

PMU therapy with 75 mg/m2 of CDDP, 10 mg/body of MMC and 400 mg/day of UFT was performed on 57 patients with terminal gastric carcinoma. The treatment resulted in CR in 2, PR in 9, MR in 1, NC in 16 and PD in 9 of 37 patients with evaluable cases, with a response rate of 30% (11/37 patients). In the 11 responders, the mean disease-free interval was 6.6 months with a median interval of 5 months, and the mean survival period was 9.2 months with a median survival period of 6 months, while in the 46 non-responders, the mean survival period was 6.7 months with a median survival period of 5 months. In all patients, the mean survival period was 7.1 months with a median survival period of 6 months. Adverse reactions to the treatment included gastrointestinal disturbance observed in 77%, nephrotoxicity in 14%, and myelotoxicity in 26% of the patients, but all reactions became normalized during the course of observation. These results have led to the conclusion that PMU therapy may be an effective treatment for terminal gastric carcinoma.