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Background Blood pressure (BP) variability has reportedly been a risk factor for various clinical events. To clarify the influence of BP visit‐to‐visit variability on adverse events in patients with nonvalvular atrial fibrillation, a post hoc analysis of the J‐RHYTHM Registry was performed. Methods and Results Of 7406 outpatients with nonvalvular atrial fibrillation from 158 institutions, 7226 (age, 69.7±9.9 years; men, 70.7%), in whom BP was measured 4 times or more (14.6±5.0 times) during the 2‐year follow‐up period or until occurrence of an event, constituted the study group. SD and coefficient of variation of BP values were calculated as BP variability. Thromboembolism, major hemorrhage, and all‐cause death occurred in 110 (1.5%), 121 (1.7%), and 168 (2.3%) patients, respectively. When patients were divided into quartiles of systolic BP‐SD (P =0.015 for thromboembolism; HR, 2.60, 95% CI, 1.36–4.97, P =0.004 for major hemorrhage; and HR, 1.85, 95% CI, 1.11–3.07, P =0.018 for all‐cause death) after adjusting for components of the CHA 2 DS 2 ‐VASc score, warfarin and antiplatelet use, atrial fibrillation type, BP measurement times, and others. These findings were consistent when BP‐coefficient of variation was used instead of BP‐SD. Conclusions Systolic BP visit‐to‐visit variability was significantly associated with all adverse events in patients with nonvalvular atrial fibrillation. Further studies are needed to clarify the causality between BP variability and adverse outcomes in patients with nonvalvular atrial fibrillation. Registration URL: https://www.umin.ac.jp/ctr/ ; Unique Identifier: UMIN000001569.

Background To clarify the influence of hypertension and blood pressure ( BP ) control on thromboembolism and major hemorrhage in patients with nonvalvular atrial fibrillation, a post hoc analysis of the J‐ RHYTHM Registry was performed. Methods and Results A consecutive series of outpatients with atrial fibrillation was enrolled from 158 institutions. Of 7937 patients, 7406 with nonvalvular atrial fibrillation (70.8% men, 69.8±10.0 years) were followed for 2 years or until an event occurred. Hypertension was defined as a systolic BP ≥140 mm Hg, a diastolic BP ≥90 mm Hg, a history of hypertension, and/or antihypertensive drug use. Hypertension was an independent risk factor for major hemorrhage (hazard ratio 1.52, 95% CI 1.05–2.21, P =0.027) but not for thromboembolism (hazard ratio 1.05, 95% CI 0.73–1.52, P =0.787). When patients were divided into quartiles according to their systolic BP at the time closest to the event or at the end of follow‐up (Q1, CI 1.75–4.74, P CI 1.02–2.53, P =0.041) after adjustment for components of CHA 2 DS 2 ‐ VAS c score, warfarin use, and antiplatelet use. A systolic BP of ≥136 mm Hg was an independent risk factor for thromboembolism and major hemorrhage. Conclusions BP control appears to be more important than a history of hypertension and baseline BP values at preventing thromboembolism and major hemorrhage in patients with nonvalvular atrial fibrillation. Clinical Trial Registration URL : http://www.umin.ac.jp/ctr . Unique identifier: UMIN 000001569.

Although abdominal perforator flaps based on a cutaneous branch of the deep inferior epigastric artery (DIEP flaps) have many advantages, preparing these flaps is technically difficult and requires great skill, especially as the portion of the artery running under the anterior rectus abdominis sheath must be operated upon "blind". To allow easier preparation and elevation of a DIEP flap pedicle, we propose that the arterial perforator should: 1) be more than 1.0 mm large; 2) run a straight intramuscular course, parallel to the rectus abdominis m. fibers, with no large muscular branches; and 3) have only a short portion running immediately under the anterior rectus abdominis sheath. We examined 329 perforators (more than 0.5 mm in diameter at the anterior sheath) in 66 rectus abdominis mm. from 33 cadavers among them: 1) 52 "large" perforators were over 1.0 mm in diameter; 2) 107 "suitable" perforators ran parallel to the muscle fibers without giving off large muscular branches; and 3) 35 "ideal" perforators combined these characteristics. The ideal perforators were usually located in the mid-abdominal region, 10-30 mm lateral to the umbilicus. The suitable perforators were usually present, often in combination with the ideal perforator(s), in a restricted area 20 mm cranial and 40-50 mm lateral to the umbilicus. We classified the course and ramification pattern of the deep inferior epigastric a. into six patterns, depending on whether the anastomosis was sited in the medial or lateral branch and the level at which the branches originated.

Decreasing susceptibility to zidovudine (ZDV) has been described in persons infected with human immunodeficiency virus (HIV) type 1 who are receiving ZDV therapy. However, the clinical significance of decreased ZDV susceptibility remains unclear. In this study, HIV isolates obtained from children with symptomatic HIV infection treated with ZDV were monitored for their susceptibility to the antiretroviral agent and correlated with disease progression. Using a peripheral blood mononuclear cell-based assay to measure ZDV susceptibility, we evaluated HIV isolates from 19 children (mean age, 6.8 years; range, 5 months to 12 years) during ZDV therapy for susceptibility to ZDV. Of the 19 children studied, 10 continued to have susceptible HIV strains during ZDV treatment, and 9 acquired resistant viruses. All eight isolates from children without previous exposure to ZDV were initially susceptible. After a median of 11 months of ZDV therapy, three (38%) of these eight children had acquired resistant HIV strains (defined as ZDV susceptibilityor = 10 mumol/L). Children with resistant strains had worse clinical outcomes than children whose viruses remained susceptible, as determined by a 50% decline in absolute CD4+ cell counts after 1 year of treatment, failure to thrive, or death. Children with resistant viruses who were given alternative antiretroviral therapy frequently responded to the new treatment with improved growth and stabilization of their HIV-related disease. These data suggest that, in HIV-infected children, ZDV-resistant HIV strains are associated with diminished drug efficacy and more rapid disease progression.

Constitutional lipid peroxidation in randomly selected 32 cases of clinically advanced carcinoma from human gastrointestinal tract (20 cases), breast (8 cases) and kidney (4 cases) was examined histochemically in frozen sections using cold Schiff's reagent. Only two cases of gastrointestinal carcinoma were positive by the reagent. Non-cancerous parenchymal cells were negative. These findings suggest that detectable constitutional lipid peroxidation seldom occurs in either cancerous or normal tissues. The capacity for normal and neoplastic tissues to undergo lipid peroxidation was also studied by incubation with an iron-NADPH pro-oxidant system. Normal parenchymal cells showed, to various degrees, a positive reactivity. In gastrointestinal carcinoma, 6 out of 7 cases of well differentiated adenocarcinoma reacted positively, whereas 2 out of 8 cases of moderately to poorly differentiated adenocarcinoma disclosed weakly positive reactions. Mucinous adenocarcinomas (4 cases) were all negative. Signet-ring cell carcinoma (1 case) was positive. One out of 8 cases of breast cancer also showed positive reaction. Four renal cell carcinomas were all negative. Cancer cells have lower capacity to undergo lipid peroxidation than normal cells, when the iron-NADPH pro-oxidant system was employed. In gastrointestinal carcinoma, the ability to undergo lipid peroxidation by the iron-NADPH pro-oxidant seems to be correlated with their histological differentiation. This fact may suggest that differences in lipid composition or the NADPH enzyme system exist between well differentiated and poorly differentiated gastrointestinal malignancies.

Liver regeneration after surgical resection is important. The present study was designed to understand the effect of background liver damage on the rate of liver tissue regeneration after hepatectomy and the mechanism of any defective regeneration.The subjects were 40 patients who underwent liver resection. They comprised 22 patients with chronic viral hepatitis-hepatocellular carcinoma (liver damage group) and 18 patients with hepatic metastases from colorectal cancer (normal liver group). Liver regeneration was evaluated by histopathological and immunohistochemical examination of the surgically resected tissue and by CT-scanning of the regenerated liver mass. The resected liver specimens were stained for c-met, gp-130 and nuclear factor-kappaB (NF-kappaB) proteins.Liver regeneration was significantly less in the liver-damage group than in the normal-liver group. Histopathological examination showed marked inflammatory cell infiltration in the liver-damage group. Expression of c-met, but not gp-130, was significantly higher on parenchymal cells of the liver-damage group than the normal-liver group. NF-kappaB expression in parenchymal liver cells was significantly higher than in non-parenchymal cells of the normal-liver group. In the liver-damage group, liver regeneration correlated negatively with the staining intensity of NF-kappaB protein in non-parenchymal cells. These findings suggest that non-parenchymal cells are constitutively activated in the damaged liver, probably explaining the refractoriness of hepatocytes to cytokine-induced proliferation after hepatectomy, in spite of increased receptor (c-met) expression.The refractory response of injured hepatocytes to cytokines may explain the impaired postoperative liver regeneration in patients with damaged liver.

Three different polypeptides capable of stimulating histamine release from mast cells were isolated from human whole saliva, using heparin-gel chromatography followed by reversed-phase HPLC. The amino acid sequences of these peptides were shown to be identical to those of histatins 1, 3 and 5.

A number of studies have indicated that cholecystokinin type A receptor (CCK-AR) plays a crucial role in postnatal pancreatic proliferation and blood glucose regulation through stimulating insulin secretion. The Otsuka Long-Evans Tokushima Fatty (OLETF) rat has been shown to possess poor pancreatic proliferation (PPP) capability after pancreatectomy (Px). Here we have constructed a congenic strain which introgressed an OLETF-derived 18.5 cM genomic fragment identified in our previous quantitative trait locus (QTL) analysis as a locus responsible for PPP into normoglycemic F344 genetic background The introgressed region includes CCK-AR null mutation. After Px, the congenic rat showed weak pancreatic proliferation equivalent to that of the OLETF rat. Furthermore, post-surgery non-fasting blood glucose levels for the congenic rats are significantly higher in comparison with the F344 rats. At 28 days after Px, the congenic rats also showed lower blood insulin levels than the F344 rats. These results further provide the genetic evidence that 1) CCK-AR is essential for pancreatic regeneration; 2) impaired pancreatic proliferation mediates the development of hyperglycemia.

Liver metastasis is a common progression of pancreatic carcinoma, but an effective chemotherapy has not been established. The purpose of this study was to examine the efficacy and safety of a hepatic arterial infusion of 5-FU in patients with liver metastasis from pancreatic carcinoma.Thirteen patients were enrolled in a pilot study of a hepatic arterial infusion of 5-FU therapy. They received 5-FU for 5 days at a dose of 500 mg/m2/day by continuous hepatic arterial infusion every 4 weeks.One patient showed a partial response, while 6 showed no change. Of these 6 patients, 2 showed a minor response. The overall response rate was 8% (95% confidence interval: 0-22%). Nausea and vomiting were the most common types of toxicity. Three patients (23%) had hepatic arterial occlusion. There were no life-threatening toxicities or complications. The overall median survival time was 15.9 weeks.Hepatic arterial infusion of 5-FU in patients with liver metastasis from pancreatic carcinoma is tolerable but is minimally effective at this dose and schedule. The schedule of administration should be modified.

Chemoradiation therapy is widely indicated to patients with locally advanced pancreatic carcinoma, though the capability of radiotherapy alone is not assessed enough. The purpose of this study is to clarify the efficacy and safety of a more intensive radiotherapy for those patients.Fifteen patients were enrolled in a feasible phase II study of treatment with intraoperative radiation therapy (25 Gy), followed by conformal external-beam radiation therapy (40 Gy in 20 fractions, 5 times/week). The antitumor effect was evaluated on the early phase of dynamic computed tomography image.The full irradiation dose was feasible in 12 of 15 patients. The overall response rate was 40% (1 complete and 5 partial responses). Grade 3 toxicity was observed in 2 patients (13%) with nausea/vomiting or anorexia. One patient developed gastric ulcer and died of gastrointestinal bleeding 12 months after intraoperative radiation therapy. The median survival time was 11.1 months, and the 2-year survival rates were 13%. Survival for more than 2 years was observed in 2 of the 6 responders.The above radiotherapy is considered to be active for the locally advanced pancreatic cancer with acceptable toxicity, when the gastrointestinal tract is excluded from the radiation field. This should be further assessed in late phase II studies involving a large number of patients.

To evaluate morphologically and immunohistochemically the role of IgM rheumatoid factor (RF) immune complexes and complement activation in rheumatoid nodule vascular injury, a typical extraarticular manifestation of rheumatoid arthritis.Histological features such as cellular infiltration, endothelial alteration, fibrinoid degeneration, and basement membrane alterations were observed in the small vessels in rheumatoid nodules. An immunohistochemical study was also carried out.Distinct colocalization of IgM RF and terminal complement complexes (TCC: C5b-9) was observed on the luminal surface in some of the damaged endothelial cells. Immuno-electron microscopy revealed endothelial vesiculation, typical of the in vitro protective mechanism against complement attack, with deposition of not only TCC but also IgM RF. Most TCC positive endothelial cells simultaneously expressed the major complement regulatory factor, CD59.These data suggest that, in rheumatoid nodules, vascular injury mediated by complement activation involves the assembly of IgM RF on the endothelial cell surface.

To clarify a macrophage-colony stimulating factor (M-CSF) related mechanism of aseptic loosening of artificial hip joints.Synovium-like interface tissues between bone and prosthesis, regenerated pseudocapsular tissues, and synovial fluid (SF) were collected from 9 patients with loose artificial hip joint at revision surgery. Tissue distribution, production site, and SF level of M-CSF in loose hip joints were investigated by immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR), and ELISA, respectively. For a comparative assessment of the M-CSF level in loose hip joints, SF of active rheumatoid arthritis (RA) and mild osteoarthritis (OA) also were analyzed by ELISA.Immunohistochemical analysis showed the presence of M-CSF immunoreactive cells mainly in the interface tissues between bone and prosthesis and inner pseudocapsular tissues, both of which were in contact with joint fluid. RT-PCR analysis confirmed the local production of M-CSF in these periprosthetic tissues. Significantly higher M-CSF level in loose hip joint fluid than in active RA and mild OA fluid was revealed by ELISA.High M-CSF level in loose hip joint fluid suggests transportation of M-CSF from production sites to joint fluid. This indicates that not only polyethylene wear particles (reported to induce foreign body reaction at the bone-prosthesis interface), but also M-CSF, abundant in joint fluid, are transported to and affect the interface. Thus, M-CSF is locally produced in periprosthetic tissues of loose hip joints and possibly contributes to periprosthetic weakening and osteolysis via joint fluid, leading to prosthetic loosening.

We report two cases of retroperitoneal functioning paraganglioma. Case 1: A 52-year-old male patient was admitted to our hospital for further examination of pulsating abdominal pain with chest pain and headache. Overfist-size smooth-surfaced hard mass was palpated at the right upper abdominal quadrant. Catecholamine levels in serum and urine showed marked elevation. Computed tomographic (CT) scan, magnetic resonance imaging (MRI) and angiography revealed a large tumor between the right kidney and aorta. He underwent surgical removal of the tumor and histological examination revealed paraganglioma. His chief complaints disappeared postoperatively. Case 2: A 68-year-old female patient was admitted to our hospital for control of diabetes. An abnormal mass was shown ultrasonically at the left renal region by routine screening examination. A marked increase of noradrenaline in serum and urine was observed. Abdominal CT scan, MRI and angiography revealed a retroperitoneal tumor which was located adjoining to the lower pole of the left kidney. The tumor was removed transabdominally. Histopathological studies showed paraganglioma. After the operation her blood sugar and noradrenaline levels decreased to the normal range.

Non-insulin-dependent diabetes mellitus (NIDDM) is a prototypical multifactorial disease. Genetic predisposition and obesity are major risk factors for NIDDM development and the interactions between these factors are likely to be important in the etiology of this disease. The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is one of the best animal models of NIDDM, since the OLETF rat develops NIDDM with mild obesity that is very similar to human NIDDM. Therefore, the OLETF rat is a powerful model for investigating the interaction between genetic susceptibility to NIDDM and obesity. In this study, our goal was to clarify the relationship between an individual NIDDM susceptibility locus and obesity in the OLETF using a molecular genetics approach. We identified four novel quantitative trait loci (QTLs) that contribute to the susceptibility to NIDDM, none of which shows significant linkage with body weight. However, Nidd1/of on chromosome 7 and Nidd2/of on chromosome 14 have an interaction with body weight. In contrast, one locus was mapped to chromosome 10 for body weight, but not to fasting or postprandial glucose levels. These data illustrate that NIDDM and body weight are under separate genetic control in the OLETF yet interact to yield the final disease phenotype in the two Nidd/of loci. In addition, body weight could be used in place of body mass index as an indicator of obesity in our experimental system of genetic study. This study will facilitate the understanding of the complex interaction between genetic susceptibility to NIDDM and obesity.

The causes and management of postoperative fever were studied.During a four-year-period beginning in January of 1991, high fever over 38.5 degrees C max occurred in twenty-five (6%) out of 395 patients who underwent cardiovascular surgery.Nine of the patients (28%) evidenced bacteriological infections as follows; 3 cases of mediastinitis, 2 cases of respiratory tract infection, 1 case of MRSA colitis and a wound infection in one case. The three patients with mediastinitis died and the two cases of MRSA were detected from the culture of pacemaker leads. Bacteriological infection was not detected in other 18 (72%) patients with fever. However, we speculated that the clinical causes of fever in 9 out of 18 patients were as follows; catheter fever in 3 patients, acalculous cholecystitis in 2, fungus infection in 2, aseptic meningitis in one and viral myelitis in one patient. Two patients with acalculous cholecystitis recovered after percutaneous transhepatic gallbladder drainage. The causes of fever were not apparent in nine patients, however the source might be related to artificial prostheses used intraoperatively in five patients. C-reactive protein (CRP) was elevated beyond 10 mg/dl in 13 (52%) of the 25 patients. CRP increased in all seven bacteriologically positive patients and in six (32%) of the bacteriologically negative patients.Precise and prompt bacterial examinations are necessary in patients with CRP elevation because the origins of fever were bacteriological in only 28% of the patients with a high fever. Good prognoses may be obtained by suitable management in bacteriologically negative patients.

Pediatric cardiac care is costly and requires extensive resources. We studied the effect of clinical pathways on practice patterns and patient care outcomes in infants and children hospitalized for cardiac surgery.In consecutive patients admitted for selected cardiac surgical procedures before (n = 69) and after (n = 173) implementation of clinical pathways, outcomes including hospital length of stay, days in the ICU, time to extubation, ordering of blood studies, costs, and readmissions were compared. Data were analyzed for each of five cardiac surgical procedures: repair of an atrial septal defect, repair of a ventricular septal defect, division of a patent ductus arteriosus, repair of tetralogy of Fallot, and neonatal arterial switch operation to correct transposition of the great arteries.A significant reduction in length of hospital stay, including days in the ICU (decreased 1 to 2 days per admission), was achieved after the clinical pathway was implemented. Reductions in average duration of mechanical ventilation ranged from 28% for repair of a ventricular septal defect to 63% for repair of tetralogy of Fallot. The number of blood studies ordered decreased 20% to 30%. A significant reduction in hospital costs for each procedure, ranging from 16% to 29%, was also achieved with no adverse effects on patients' outcomes.Use of clinical pathways with children hospitalized for cardiac surgery can shorten length of stay in the hospital, reduce use of resources, and improve cost-effectiveness with beneficial outcomes for patients.

Five patients presenting with chronic dorsal wrist pain and diagnosed as distal posterior interosseous nerve syndrome are reported. Clinical examination revealed point tenderness of the fourth extensor compartment. The symptoms were reproduced by extreme wrist extension in all patients and by extreme flexion in three of the patients. The pain was relieved in all patients by a selective lidocaine block of the terminal branch of the posterior interosseous nerve at the wrist joint. All the patients failed to respond to nonoperative treatment and underwent surgical exploration of the nerve. The operative findings were an enlarged nerve in three patients and adhesion of the nerve to the joint capsule in five patients. A 2 cm section of the nerve proximal to the extensor retinaculum was resected. Four of the five patients had excellent pain relief and returned to full asymptomatic activity. One patient had improvement in pain and was satisfied with the outcome. A diagnosis of distal posterior interosseous nerve syndrome should be considered if the usual sources of dorsal wrist pain are eliminated.

A 32-year-old man was admitted to our hospital because a cardiac tumor had been pointed out by a physician. CT scans showed a mass lesion with irregular patterns in the right atrium. The patient had the diagnosis of a malignant cardiac or pericardial tumor and an operation was performed. The mass originated from the right atrium included massive coagulated blood, and was resected with the pericardium and the right pleura. The histological diagnosis was malignant hemangioendothelioma. We present this case because only 35 patients with cardiac malignant hemangioendothelioma were reported in Japan.

The hemorheological effects of autologous blood storage with or without the use of erythropoietin were examined before surgery for valvular disease. There was no rheological difference between patients with aortic (16 cases) or mitral (10 cases) valve disease. Before storage, the levels of hematocrit, whole blood viscosity, and especially coefficient of rheology, were lower (p0.05) in the blood stored with erythropoietin, but this difference disappeared after storage. The plasma viscosity of both groups did not change before and after storage. The viscosity of blood was equalized after the storage of blood, irrespective of the use of erythropoietin.

We treated 12 shoulders in ten patients with irreparable rotator-cuff tears by transfer of the latissimus dorsi. There were nine men and one woman. Their average age was 64.0 years and the average follow-up was 35.6 months (26 to 42). The results were excellent in four shoulders, good in four, fair in one, and poor in three. Active forward flexion improved from a preoperative average of 99 degrees to a postoperative average of 135 degrees. Osteoarthritic changes appeared in five shoulders and proximal migration of the humeral head progressed in six. EMG revealed that nine of the 12 transferred muscles showed activity which was synergistic with the supraspinatus on external rotation with abduction. We conclude that latissimus dorsi transfer can be effective in restoring shoulder function after massive irreparable tears of the rotator cuff.

A case of bilateral synchronous multilocular cystic renal cell carcinoma is reported. A 52-year-old man was admitted to our hospital for further examination of right renal mass which was found incidentally by ultrasonography. After he was examined by intravenous pyelography (IVP), computerized tomographic (CT) scan, magnetic resonance imaging (MIR) and angiography, right nephrectomy was performed under the diagnosis of right renal cancer. Histological diagnosis was multilocular cystic renal cell carcinoma. CT scan revealed a small left renal cystic lesion at that time. Ten months later enhanced CT scan revealed irregular septum in the cystic lesion. Under the diagnosis of left renal cancer, we carried out simple enucleation. Histological diagnosis was multilocular cystic renal cell carcinoma as in the right kidney. The patient has been followed up carefully. This is the third case of bilateral multilocular cystic renal cell carcinoma, which is regarded as the first synchronous one, reported in Japan.

Herbivorous voles, Microtus arvalis, have characteristics similar to herbivores in that their hepatic glycolytic enzyme activities are relatively low. The effects of a single low dose (100 mg/kg body weight) of streptozotocin (STZ) in voles were studied and the difference in sensitivity to or toxicity of STZ in voles and C57BL/6 mice was compared. In voles which received STZ, the cumulative incidence of glycosuria reached 53% by 4 weeks after administration. The diabetic voles showed marked increases in their blood glucose and plasma free fatty acid concentrations and a significant decrease in plasma immunoreactive insulin concentrations. Their hepatic hexokinase, glucokinase, glutathione peroxidase and glutamate dehydrogenase activities decreased significantly and lesions were widely observed in the liver, kidney and pancreas. The activities of glutathione peroxidase, a scavenger of H2O2, decreased significantly in their liver and pancreas. These changes were not observed in C57BL/6 mice which received STZ. The higher sensitivity to and toxicity of STZ in voles than in mice are considered to be caused by the characteristically low activities of glycolytic enzymes and glutathione peroxidase in the tissues of voles. Voles may be a good model for studying the mechanisms of cytotoxicity by STZ in herbivorous animals.

On the basis of previous studies showing an association between hepatitis B surface antigen (HBsAg) positivity and radiation exposure in atomic bomb (A-bomb) survivors, we investigated further the active state of hepatitis B virus (HBV) infection by incorporating tests for hepatitis B e antigen (HBeAg) and hepatitis B e antibody (anti-HBe) and HBsAg subtypes into our biennial health examinations. Among 6548 A-bomb survivors for whom HBsAg was assayed between July 1979 and July 1981, 129 persons were HBsAg positive. HBeAg and anti-HBe were measured in 104 of these persons and subtypes of HBsAg in 98 persons. Among those exposed to radiation (average liver dose 0.58 Sv), the odds ratio of HBsAg positivity tended to increase with radiation dose (P for trend = 0.024). The P values for association between the prevalence of HB e antigen and radiation dose and between the prevalence of anti-HBe and radiation dose were 0.094 and 0.17, respectively. The HB antigen subtype adr was predominant over other subtypes in both Hiroshima and Nagasaki, but the distribution of subtypes did not seem to differ in relation to radiation dose. These results suggested that A-bomb survivors remain in an active state of HBV infection and that the mechanism(s) of seroconversion may be impaired.

The ultrastructure of lens fiber cytoskeleton was studied by quick-freezing and deep-etching. Lenses of 5 Wistar male rats were divided into lens cortex and lens nucleus. Filamentous structures were clearly observed in the cortical fiber cells, which had diameters in 10 approximately 15 nm or about 5 nm. They showed a meshwork structure. On the other hand, the filamentous structures showed a linear, dense, and laminar pattern in the nuclear fiber cells. These ultrastructural changes of cytoskeletons may be related to the elongation and differentiation of lens fiber cells and may be important for maintaining transparency of the lens.

To clarify the role of postoperative radiotherapy for adenoid cystic carcinoma of the tracheobronchial system (ACC), we analyzed patients treated at the National Cancer Center Hospital, Tokyo. Seven patients with ACC were treated with resective surgery and postoperative radiotherapy from 1962-1990. None of the primary lesions was completely surgically resected. Postoperative irradiation was delivered by standard fractionation at a dose range of 49.2-72 Gy. Four of seven patients lived more than 5 years, up to 21 years, without local recurrence. In contrast, three other patients who showed recurrence within 2 years died of disease before 5 years. Three of four patients who received postoperative irradiation of 60 Gy or more attained local control. One of three patients who received less than 60 Gy failed locally. A high dose of postoperative radiotherapy for patients with a positive surgical margin of ACC seems to improve local control and result in long-term survival.

Between 1983 and 1992, 38 patients with 44 tumors of bone and soft tissue sarcoma were treated by hyperthermia combined with radiotherapy or chemotherapy. The overall response rate in this series was 48% (21/44). The average time for heating to 42 degrees C and the average maximum temperature did not correlate with the local effect. The percentage of the low density area on CT images and the average maximum temperature were well correlated. When 100% necrosis was evaluated as CR and up to 50% necrosis as PR, the local response rate was elevated from 42% to65%. Bone and soft tissue sarcomas are good targets for hyperthermia combined with radiotherapy and chemotherapy. Some tumors indicated for this study were too large to heat with the present heating apparatus. Percent low density and percent necrosis were correlated to some degree, but adoption of this phenomenon as a criterion for evaluation should be considered carefully.

Human immunodeficiency virus type 1 (HIV-1) isolates from perinatally infected infants and children were examined for syncytium-inducing (SI) capacity. All isolates from 14 infants1 year old had non-syncytium-inducing (NSI) HIV-1 phenotypes. Within their first year, 10 infants progressed to AIDS and 3 died. Of isolates from 26 children2 years old, 13 had SI HIV-1 phenotypes and 13 had NSI strains. Children with SI virus had significantly lower CD4+ cell counts standardized for age and were significantly older than those with NSI strains (P = .008 and .001, respectively); the effect of viral phenotype on CD4+ lymphocytes could not be detected independent of age. In another group, children with SI strains were more likely to show in vitro zidovudine resistance. Results suggest a biphasic response to HIV infection in children. Progression to AIDS may occur rapidly in infants with NSI HIV-1, but older children tend to have SI phenotypes and lower CD4+ lymphocyte counts and more often show zidovudine resistance.

Phospholipid antibodies (lupus anticoagulant, cardiolipin) are associated with a syndrome of repeated fetal loss. Mothers with phospholipid antibodies are currently being treated with either prednisone, aspirin, or heparin to prevent fetal death. We describe a neonate whose mother had cardiolipin antibody and recurrent fetal loss and was treated with prednisone and aspirin. Thrombosis was noted in placental fetal vessels. Thromboses developed in the infant's aorta, left renal artery, middle cerebral artery, and superior sagittal sinus. Infants of phospholipid-positive mothers may have vascular thrombosis and should be carefully monitored for signs of thromboembolism.

Chemotherapy with a combination of synthetic ACTH (ACTH-Zn) and valproic acid (VPA) induced remarkable hypofibrinogenemia in three children (5 months, 8 months, and 5 years and 10 months old) with intractable epilepsy. The lowest blood fibrinogen (Fbg) levels by this combination therapy were 22, 51 and 64 mg/dl (mean 45.7 mg/dl), respectively. These levels occurred, when ACTH-Zn was administered at an average dose of 0.33 mg/day (0.03 mg/kg/day) and the mean blood concentration of VPA was 59.7 micrograms/ml. With the administration of VPA without ACTH-Zn, the lowest blood Fbg levels were 232, 108 and 170 mg/dl (mean 170 mg/dl), respectively. The mean blood concentration of VPA was 109.0 micrograms/ml. The inadvertent-effects associated with this combination therapy consisted of thrombocytopenia (59,000/microliters) in one case and a mild GPT increase (65-109 IU/l) in three cases. However, all these changes were transient. No bleeding tendency was detected clinically, when this hypo-Fbg-emia appeared. The concentration of VPA and the blood level of Fbg were found inversely correlated with a correlation coefficient of -0.22 (p0.01) in 150 serum samples from 91 patients with childhood epilepsy treated with VPA without ACTH-Zn. In the three cases presented, the combination with ACTH-Zn resulted in considerably lower blood Fbg levels than those predicted from the blood VPA concentrations. This indicates that the combination of ACTH-Zn and VPA induces a further decrease of Fbg in blood. The reason why hypo-Fbg-emia results from this combination therapy is unknown.(ABSTRACT TRUNCATED AT 250 WORDS)

This paper presents our preliminary experience with three-dimensional (3-D) treatment planning using the cine mode display of magnetic resonance imaging (MRI) for brain tumors. MRI images, viewed from the direction of the source of radiation, are reconstructed at consecutive 5 mm intervals and superimposed on the 3-D skin surface image. Tumors and normal structures can be visualized as is, without delineating them. Limitations of the technique are also discussed.

Clinicopathologic study of six cases of early invasive colorectal carcinoma metastatic to lymph node was performed in order to elucidate possible characteristics relating to the risk of metastasis, with particular attention to the growth pattern of the primary tumor. All of the cases had at least one of the well-known risk factors for lymph node metastasis, including moderately or poorly differentiated histologic characteristics, considerable degree of submucosal invasion, and lymphatic invasion. An interesting finding of the present study was the identification of a nonpolypoid growth pattern with no concomitant adenomatous tissue, which seemed to be different from that of "malignant polyps" of previously reported cases showing adenoma-carcinoma sequence. This unique growth feature was found in all of the cases. Therefore, in addition to the accepted risk factors, nonpolypoid growth pattern and absence of adenomatous component may be risk factors predictive of nodal metastasis in patients with early invasive colorectal carcinoma.

A rare alpha-fetoprotein (AFP)-producing carcinoma that originated in the rectum of a 54-year-old man is reported. High levels of AFP are found in the serum (5,126 ng/ml) and homogenate of the tumor tissue (2,600 ng/g). Two morphologic patterns were noted in the tumor. One was that of well differentiated tubular adenocarcinoma and the other was more polymorphous, in which the tumor cells grow in a solid-sheet with occasional glandular and papillary structures. Hyaline bodies and Schiller-Duval body-like structures were also found in the polymorphous area. There was a gradual transition between the well differentiated and the polymorphous area. AFP was positive in the polymorphous area and negative in the well differentiated area on immunohistochemical examination. These morphologic and immunohistochemical characteristics may suggest a differentiation toward embryonal carcinoma of the polymorphous component. Moreover, the polymorphous component showed marked vascular invasion and metastasis of liver as well as regional lymph nodes. AFP-producing carcinoma cells may be more aggressive than ordinary adenocarcinoma.

An 8-year-old boy with infected urachal cyst presenting with macroscopic hematuria, pain on urination and high fever attack is reported. He had recurrent episodes of cystitis. At admission, a quail-egg sized solid tumor was palpated in the midline of his lower abdomen. The urine was infected. Ultrasonographic examination revealed an oval tumor 2 x 2.7 cm in diameter at the dome of the bladder with a thin funicular structure running toward the umbilicus. Cystoscopy revealed a round tumor covered with hyperemic epithelia. Transurethral biopsy revealed no malignant lesions of the epithelia. Partial cystectomy with excision of the funicular urachal ligament was performed. The pathological findings were consistent with persistent urachus with chronic inflammation. We reviewed 210 cases of infected urachal cysts reported in the Japanese literature.

Thirteen cases of ulnar nerve neuropathy at the wrist are presented. They include four cases of pure motor paresis affecting the ulnar-innervated intrinsic muscles, one case of pure sensory deficit and eight cases of mixed motor and sensory deficiency. A cyst was revealed by preoperative ultrasonography in two cases and by computerized tomography in one of them. The cause of ulnar nerve neuropathy was a tumor or tumor-like mass in six cases, long-time cycling in three cases and unknown in three cases. Surgery was performed in ten cases. Recovery of the nerve palsy was obtained in all except one case.

Sixty-eight patients with endobronchially invading recurrence of esophageal cancer after resective surgery were treated with radiotherapy from 1966 to 1988. The mean interval between resective surgery and diagnosis of recurrence was 11.1 months, that was significantly shortened in a3 group. The dose of radiation for recurrence ranged from 2 to 70.3 Gy, with a mean dose of 42.6 Gy. The mean survival time after treatment of recurrence was 4.9 months. The dose of radiation was found to have a positive correlation with survival time. The cause of death was bleeding in 20 patients, and respiratory failure in 36. High dose of radiation was thought to induce high incidence of bleeding. The results indicated that external beam radiotherapy with conventional fractionation was not so much effective for the recurrence.

A case of epithelial myoepithelial carcinoma is reported. Histologically, this tumor shows tubular and solid growth pattern. The inner layer of the tubules is composed of cells with an eosinophilic cytoplasm that is surrounded by cells with clear cytoplasms. Clear cells also manifest a solid growth pattern. Immunohistochemical and electron microscopic examinations has revealed that the cells with an eosinophilic cytoplasm have the characteristics of the ductal epithelium and that the clear cells have the characteristics of the myoepithelium. Immunohistochemically, keratin positive clear cells and S-100 protein positive ductal cells were found in our case. This suggests the existence of cells having both ductal and myoepithelial characteristics and this inspected tumor had derived from multipotential cells of intercalated ducts.

We have studied the effect of intraarteric infusion chemotherapy with missile chemotherapy, induced hypertensive chemotherapy and/or two-route infusion chemotherapy in 14 liver tumors (7 cases with liver metastasis from gastric cancer, 3 cases with liver metastasis from colonic cancer, 4 cases with hepatoma). Results indicated that PR in 6 (46.1%) out the 13 evaluated cases. The toxicity was not evident except for slight bone marrow depression with 5 cases and a low grade fever with 2 cases. These results indicate that intraarterial infusion chemotherapy with drug delivery system can be considered one of the treatment therapies available for a nonresectable tumor.

In cases of treating a pancreatic cancer, an aneurysm and thrombus of the abdominal aorta, necrosis of the vertebral body, and damage to the peripheral nerves can be caused by intraoperative radiotherapy (IORT). These aftereffects have been observed in tests conducted in experimental animal reported by Colorado State University. Similarly, our clinical experiences have led us to set safety guidelines to prevent damage due to IORT. The safety level of a radiation dose for IORT alone is limited to 30 Gy, and for IORT combined with external beam radiotherapy, from 20 Gy (IORT) plus 50 Gy (EBRT). Using these parameters, among 58 cases of a pancreatic tumor treated by IORT, only one case subsequently developed a pseudoaneurysm at the stump of splenic artery.

Considering a high potential of biological malignancies of Borrmann 4 type carcinoma (abbr., Borr. 4) of the stomach, preoperative induction (neoadjuvant) chemotherapy was applied to patients with Borr. 4 as an initial therapy. Anticancer drugs used in this study were FAM-OK432, sequential MTX-5Fu or UFT-M through aortic infusion or induced hypertension chemotherapy (IHC) in order to obtain selective enhancement of drug delivery into tumor tissue. These trials were carried out on 24 patients who had Borr. 4 type carcinoma. The response to neoadjuvant chemotherapy showed CR in 1 case, PR in 3 cases and MR in 4 cases. The objective improvement except the primary gastric lesion showed shrinking of distant metastatic lymph nodes along paraaorta or Virchow of 50% (5/10), disappearance of pleural or peritoneal fluids 85. 7% (6/7) and marked decrease of tumor marker such as CEA, CA19-9 or CA125 100% (12/12). In one of 5 cases showing morphological improvement of primary gastric lesion, no viable cancer cells were seen in the stomach associated with multiple foci of granulofibromatous lesion of regional nodes. In 17 cases of 24 total gastrectomy was done with extended lymphadenectomy (R2-R3). While there was no difference in the median survival time (MST) among curable resection group, MST of non-curable resection group with neoadjuvant chemotherapy showed a fairly good prognosis for 14 months as compared to that of 4 months without chemotherapy. As for disease-free survival, patients whose tumor showed a high response to neoadjuvant chemotherapy had a good prognosis in non-curable resection group (p less than 0.01). In conclusion our results demonstrated that patients whose tumor were effectively destroyed by neoadjuvant chemotherapy against Borr. 4 carcinoma of stomach had an improved prognosis.

Ultrasonographic imagings of non-tumor disorders in extremities were reviewed and discussed. All cases underwent surgery. In our retrospective evaluation, US was found to be effective in cases of tendon injuries, articular osteochondritis, tenosynovitis and the displacement of chondral navicula in infantile club foot, etc.

In approximately seven years, 134 patients with 161 tumors were treated by hyperthermia combined with radiation or chemotherapy at our department. The primary tumors were breast cancer, head and neck cancer, and soft tissue tumors in most patients. Adenocarcinoma was the most frequent, followed by squamous cell carcinoma and soft tissue sarcoma. The local response rates for primary inoperable advanced, metastatic, and local recurrence of breast cancer were 88% (7/8), 50% (10/15), and 86% (18/21), respectively. The local response rate of 39 tumors of neck lymph nodes was 49% (19/39). A total of 26 tumors of bone and soft tissue were treated. Five tumors showed CR and six PR, for a total response rate of 42%. Among 20 patients with malignant melanoma, CR and PR were 25% (5/20) and 30% (6/20), respectively. The local response rate for all patients with superficial and shallow-seated tumors was 58% (94/161). In some tumors classified as showing NR, complete disappearance of tumor cells was demonstrated by a post-treatment histological examination. The efficacy of hyperthermia, when evaluated solely on the basis of tumor size, is likely to be underestimated.

With the purpose to avoid the risk of homologous transfusion, autologous blood transfusion was performed in 26 patients who underwent transurethral resection of the prostate (TUR-P). Autologous blood (200-400 ml/time, 1-3 times, total 200-800 ml, mean 381 ml) was predeposited 4 days to 3 weeks prior to elected TUR-P and was transfused during or just after the operation. Since the start of this program in February 1988, homologous transfusion rate was decreased to 13.1%, whereas it has been 22.3% in 203 cases between January 1984 and January 1988. The mean hemoglobin level fell to 81.6% of the predeposition level. However, the hemoglobin level recovered to 90.1% one month after operation. The circulatory condition of the patients with autologous transfusions was stabler than that of the patients with homologous transfusion or no transfusion. No clinical hemostatic problems occurred. In cases with mild to moderate volume resection of the prostate, this autologous blood transfusion is recommended.

In order to evaluate differences between the initial manifestations of acute myocardial infarction (AMI) in diabetics (DM) and non-diabetics (N-DM), 94 consecutive AMIs (DM 40, N-DM 54) were studied over a four-year period. Cases with abrupt onset associated with chest pain and/or discomfort in the areas of the chest and back were classified as the typical group (I). All other cases were classified as the atypical group (II). In subjects over the age of 60, 12 out of 33 DM had atypical manifestations, but only 3 out of 29 N-DM (p less than 0.05). In subjects aged 59 or less, the incidence of atypical cases was similar in the DM and N-DM groups. The initial symptoms of AMI were not correlated with type or location of infarction, nor with the type of treatment or presence of the ankle jerk reflex. Pre-infarction symptoms were present in 69% of Group I and 74% of Group II DM subjects. In Group II, 5 out of 16 patients had a history of typical angina, but had no chest pain at the onset of infarction. The post-AMI mortality within one month was 15% in the DM and 18% in the N-DM group. It was 14% in Group I and 25% in Group II. Mean CPK did not differ statistically between Group I and Group II. However, the Peel prognostic index was 11.0 +/- 5.1 for Group I and 15.5 +/- 5.0 for Group II (p less than 0.05) in subjects over the age of 60.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of exchange transfusion with fresh whole blood in septic shock infants was evaluated. Endotoxin was positive in 8 of 10 infants and completely removed from 6 by exchange transfusion. All 6 infants with negative endotoxins after exchange transfusions survived, but 2 with positive reactions died despite the exchange transfusion. Staphylococcus aureus was cultured in the blood from 2 infants with negative reactions and one of them survived. These findings suggested that the clearance of endotoxin has an important role in exchange transfusion among septic shock neonates.