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A 44-year-old man with alcohol-induced chronic pancreatitis was referred to our institute for evaluation of severe anemia. The hemoglobin was 2.6g/dl. The results of upper gastrointestinal and colonic examination were negative. Computed tomography and ultrasound examination revealed a pseudocyst in the head of the pancreas. A pseudoaneurysm of the anterior superior pancreaticoduodenal artery shown by angiography appeared to have caused gastrointestinal bleeding by rupturing into the pancreatic cyst connected to the main pancreatic duct. A pyrorus-preserving pancreaticoduodenectomy was performed successfully.

The effects of centrally administered interleukin-1 beta (IL-1) or platelet activating factor (PAF) on adrenocorticotropin (ACTH) and catecholamine secretion, blood pressure and heart rate were examined to determine if these agents stimulate similarly the hypothalamic-pituitary-adrenal (HPA) axis or the sympathetic-adrenomedullary system. Intra-third ventricular administration of IL-1 (50, 200 ng) evoked significant ACTH secretion. Centrally administered IL-1 (50 ng) elevated plasma noradrenaline and adrenaline levels, systolic blood pressure and heart rate. Plasma ACTH, noradrenaline and adrenaline levels were also increased by the higher dose (200 ng) of IL-1 while systolic blood pressure and heart rate were not affected. Intra-third ventricular administration of 9 micrograms of PAF elevated the plasma ACTH level while 3 micrograms of PAF did not stimulate ACTH secretion. Neither dose of centrally administered PAF affected any plasma catecholamine level or systolic blood pressure. These results suggest that central IL-1 stimulates both the HPA axis and the sympathetic-adrenomedullary system, that a higher dose of IL-1 stimulates a mechanism to antagonize the elevation of blood pressure and heart rate and that central PAF is not involved in the control of the sympathetic-adrenomedullary system. Thus, IL-1 and PAF do not interact in the brain, although they interact peripherally.

Lymphokine activated killer (LAK) cells can destroy not only tumor cells but also syngeneic liver cells. In this study, the effects of passive transfer of LAK cells on liver regeneration were examined by the 3H-thymidine uptake and bromodeoxyuridine (BrdU) labeling methods after resection of 70% of the volume of the liver. LAK cells were infused 12h after hepatectomy and the effects on regeneration of liver cells were examined 36 h later. The transfusion of LAK cells induced significant inhibition of liver regeneration at a dose of 5-10 x 10(7) cells. Neuraminidase treatment of lymphocytes is desirable to enhance the selective entrapment of LAK cells into the liver. When LAK cells were treated with neuraminidase (0.5 units/ml), and transfused into hepatectomized mice, more potent suppression of liver regeneration was induced in comparison with the same dose of LAK cells. The intraperitoneal injection of recombinant interleukin 2 (rIL-2) after partial hepatectomy also inhibited the regeneration of remnant liver. From these results, lymphocytes such as LAK cells appear to regulate liver regeneration.

The distribution of lectin receptors in the human tonsil was studied using 16 biotinylated lectins. The avidin-biotin-peroxidase complex (ABC) method was used on frozen and paraffin-embedded tissue sections. Cell suspensions were also analysed by dual flow cytometry using respective fluorescein isothiocyanate-conjugated lectins and phycoerythrin-labeled anti-CD3 and anti-human immunoglobulin. Frozen sections fixed with acetone and paraffin-embedded materials fixed in three solutions were compared for lectin affinity; ethanol-fixed sections gave best results followed by frozen and buffered formalin-fixed ones, then nonbuffered formalin. Con-A, RCA-1, LcH, WGA, MPA, PHA, PSA, PNA, SJA and GSA-1 reacted with all tissue components of the tonsil in immunohistochemical studies, but binding intensity was fixative dependent. Binding of Lotus and BPA to lymphocytes was limited to germinal center lymphocytes. Other tissue components were also reactive but staining intensity was weaker in Lotus compared with BPA. SBA and DBA did not react with lymphocytes, but reacted with macrophages/histiocytes, vascular endothelia, and epithelial cells. LBA and LPA were constantly negative with all tissue components irrespective of fixatives. Flow cytometric analyses showed that all but three (DBA, LBA and LPA) partially or totally stained lymphocyte surfaces. Lotus receptors were expressed exclusively on B-lymphocytes.

Ten radiograph signs were assessed by two experts for their usefulness in the diagnosis of small solitary peripheral pulmonary nodules less than 3 cm. The ten categories included notching, spicula formation, pleural indentation, vascular convergence, contour, paleness, homogeneity, cavitation, air bronchogram, and calcification. The cases included 134 lung cancers and 44 benign lung lesions resected between 1972 and 1988 at the Second Department of Surgery, Okayama University Medical School. Notching, spicula formation, pleural indentation, vascular convergence, contour, and air bronchogram were useful signs in differentiating lung cancer from benign lung lesions. However, since the radiograph signs exhibited great variation in both lung cancer and benign lung lesions, a diagnostic operation is sometimes inevitable.

We recently reported that epidermal growth factor (EGF) levels in the first urine to be voided by intrauterine growth retardation (IUGR) and heavy-for-dates (HFD) infants were lower than control infants (8). In this study, we analyzed EGF receptors to reveal the mechanisms controlling EGF levels. EGF binding to fetal rat liver increased markedly from day 19-21 of gestation. Fetal rats were divided into IUGR, control and HFD groups. EGF binding to the liver in each group was as follows, IUGR; 380 +/- 57 fmol/mg protein, control; 258 +/- 47, and HFD; 545 +/- 112. The binding to IUGR and HFD rat liver was significantly greater than in the control group (p < 0.05). These data suggest that IUGR rats compensate for a lack of EGF by increased receptor expression and that HFD rats consume more EGF and have decreased urinary EGF excretion. These data also suggest that EGF is closely related to fetal growth and may play some important roles in fetal growth.

A rare case of resectable solitary pancreatic metastasis from a renal cell carcinoma is reported. The patient was a 57-year-old man who presented with epigastralgia. He had undergone a radical nephrectomy of the right side 30 months previously. The diagnosis of pancreatic metastasis was based on the patient's past history and angiographic demonstration of typical hypervascular tumor staining. Histological examination was confirmatory. The patient was successfully treated by pancreaticoduodenectomy followed by alpha-interferon administration. As of 6 months after surgery, he remains well.

Obliteration for gastric or duodenal variceal hemorrhage was performed via transileocoecal or transhepatic portal catheterization in 8 patients with portal hypertension. The patients were 6 men and 2 women, whose average age was 59 years. All of the patients had cirrhosis of the liver. The obliteration was performed as an emergency procedure in 6 cases, and 2 patients were electively treated. Transileocoecal obliteration (TIO) and transhepatic obliteration (PTO) were selected for 6, and 2 patients, respectively. Variceal bleeding was successfully controlled in all patients after completion of the therapy. One patient died after 3 months when duodenal variceal bleeding recurred. Elective surgical operations were performed on 2 patients after the initial therapy, because the vein feeding toward the varices remained. Six of the patients have survived to date without bleeding. Transient oliguria and jaundice after the therapy were noticed in 2 patients. Histological examination revealed cast formation of polymerized cyanoacrylate in the obliterated gastric varices of 2 patients. TIO and PTO seem to be safe, effective procedures to stop bleeding from ectopic varices, gastric or duodenal. This therapy is useful either to obtain accurate information about the varices or to obliterate the collateral veins in patients with ruptured ectopic varices.

<P>Effects of methanol on colony-formation of human hepatoma cells were investigated. Among five human hepatoma cell lines (Hep G2, HLE, HuH-6, HuH-7, and PLC/PRF/5), only HLE cells showed enhanced colony formation due to methanol. The effective concentrations of methanol were around 1%. The enhancement occurred in a greater degree when the cells were seeded in the culture medium containing methanol than when methanol was added 24h after the cells were seeded. Methanol itself, however, did not enhance the cell proliferation.

A case illustrating the value of aggressive respiratory training in improving the prognosis of lung cancer complicated by low pulmonary function is reported. Preoperative and postoperative respiratory training enabled the patient with chronic respiratory failure to survive a lengthy operation and eventually breathe without assistance. The patient has survived more than 71 months, and experiences only exertional dyspnea at the time of publication. Aggressive preoperative and postoperative respiratory management may make more of the growing number of lung cancer patients eligible for standard surgical procedures.

We performed a long-term follow-up of 4 patients with penile cancer who underwent hyperthermotherapy from August 1985 until August 1992. Hyperthermia was applied using a frequency of 350 MHz with a waveguide applicator twice a week for 60 min each for an average of 9.5 times (varying from 6 to 13 times). The total heating time that the temperature of urethra could be kept above 42 degrees C, was 166 min on the average (ranging from 0 to 463 min). Two patients classified as stage I according to the Jackson classification and 1 patient classified as stage IV underwent combined radiotherapy and received an average radiation dose of 53 Gy (range, 40-70 Gy). Among these patients 2 underwent combined chemotherapy with bleomycin or peplomycin. Malignant cells disappeared posttherapeutically and in August 1992, after an average of 5 years and 9 months (varying from 4 years 6 months to 6 years 10 months), the patients were free of recurrences. The one patient on stage IV had extensive invasion of the abdominal wall, but still recovered completely. One patient on stage III underwent combined chemotherapy and hyperthermotherapy, but heating had obviously been insufficient. There was a residue of malignant cells after the treatment and we performed a penectomy. Regarding functional preservation of the penis a multidisciplinary therapy incorporating hyperthermotherapy can be expected to increase the curativity. This indicates that it could induce in an advanced case, where an operation would be difficult, complete remission.

We studied whether a cardiopulmonary bypass (CPB) and a core-cooling technique could resuscitate an arrested heart, and whether this procedure benefited canine cadaveric heart transplantation. Donor dogs were subjected to brain death by an intracranial balloon technique, and then, to cardiac arrest conducted by cutting off ventilatory support. In the control group (Group 1; n = 8), arrested hearts were flushed with cardioplegic solution and harvested thereafter without any resuscitation technique. In the experimental group (Group 2; n = 8), arrested hearts were once resuscitated using CPB, and then harvested using a core-cooling technique and cardioplegia. These hearts were transplanted orthotopically. Seven of eight recipients in Group 1 were weaned from CPB, and five of them finally became independent of dopamine administration. All recipients in Group 2 were successfully weaned from CPB, and also became dopamine free eventually. In Group 2, all post-transplantation hemodynamic values such as cardiac output during the period of dopamine administration were equivalent to those of post-brain death period. Chemical analysis of the serum and myocardial muscle demonstrated no difference between groups. We conclude that CPB combined with a core-cooling technique makes it possible to utilize an arrested heart as a donor organ for transplantation.

Basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) were administered into the rat brain following unilateral fimbria-fornix transection. Both bFGF and NGF stimulated the sprouting of acetylcholinesterase (AChE) positive fibers in the hippocampus on the lesioned side. Furthermore, a small number of AChE-positive fibers were regenerated even when only the vehicle was administered. Rats treated with NGF as well as control group had only thin fibers, whereas those treated with bFGF had not only thin fibers but also thick fibers. These results indicate that intrinsic NGF is released and acts on damaged neurons directly, while bFGF acts them on directly and/or indirectly after brain injury.

<P>Measurements of the cerebrospinal fluid (CSF) flow using phase contrast cine magnetic resonance (MR) imaging were performed on a phantom, 12 normal subjects and 20 patients with normal pressure hydrocephalus (NPH). The phantom study demonstrated the applicability of phase contrast in quantitative measurement of the slow flow. The CSF flows of the normal subjects showed a consistent pattern with a to-and-fro movement of the flow in the anterior subarachnoid space at the C2/3 level, and they were dependent on the cardiac cycle in all subjects. However, the patients with NPH showed variable patterns of the CSF pulsatile flow and these patterns could be divided into four types according to velocity and amplitude. The amplitudes of each type were as follows: type 0 (n = 1), 87.6mm; type I (n = 2), 58.2mm (mean); type II (n = 6), 48.0 +/- 5.0mm (mean +/- SEM); and type III (n = 11), 19.9 +/- 1.8mm (mean +/- SEM). The decrease of the amplitudes correlated to a worsening of the clinical symptoms. After the shunting operation, the amplitude of to-and-fro movement of the CSF increased again in the patients with NPH who improved clinically. Some of the type III cases were reclassified type II, I and 0 and also one of the type II cases changed type I after the shunting operation. We conclude that the phase contrast cine MR imaging is a practically and clinically applicable technique for the quantitative measurement of the CSF flow.</P>

Fifteen patients with Japanese cedar pollenosis were examined for lower airway function. Flow-volume patterns obtained from flow-volume and volume-time curves during the pollen season (March) and outside of the pollen season (June) were evaluated. In a previous report we classified maximal expiratory flow-volume (MEFV) curves in five patterns from A to E. In the present study, the patterns did not vary between the two periods except in one patient. Eleven patients out of 15 showed type E patterns, in which the flow-volume curve was concave along its entire course. In most of the patients with severe or moderate symptoms of allergic rhinitis only during the pollen season, the curve shifted to the right, but the parameters of the curves did not increase significantly outside of season. These findings suggest that patients with Japanese cedar pollenosis suffer from continuous latent peripheral airway obstruction. Extremely slight changes in the flow rate were detected by comparing the curves obtained during the two periods.

To assess the usefulness of flowcytometric monitoring in the early detection of acute allograft rejection, we studied surface markers of graft infiltrating lymphocytes, coronary sinus blood lymphocytes and peripheral blood lymphocytes after rat heart transplantation. Fisher rats served as donors and Lewis rats as recipients. Among recipients that received no immunosuppression, grafts were removed 2 days after transplantation (Ongoing Rejection Group: n = 7) and on the day of terminal rejection (Rejection Group: n = 7). The Immunosuppression Group (n = 7) was treated with cyclosporine A at a dose of 3 mg/kg/day intramuscularly for 14 days. The following two color analyses were studied: OX8 (anti-CD8) with OX39 (anti-interleukin 2 receptor; IL2R), W3/25 (anti-CD4) with OX39, W3/25 with OX8. Histological grading demonstrated no significant difference between the Ongoing Rejection Group and the Immunosuppression Group, which showed mild rejection (1.29 +/- 0.27 versus 1.14 +/- 0.24). The proportion of CD8(+)IL2R(+) graft infiltrating lymphocytes showed a more significant increase in the Ongoing Rejection Group than in the Immunosuppression Group (32.1 +/- 3.05 versus 20.6 +/- 9.02; p < 0.01). The proportion of CD8(+) IL2R(+) coronary sinus blood lymphocytes also showed significant increase in the Ongoing Rejection Group compared with the Immunosuppression Group (4.63 +/- 1.91 versus 2.52 +/- 1.60; p < 0.05). These results suggest that this technique can detect acute allograft rejection earlier than endomyocardial biopsy, before the phase in which histological findings become evident.

We evaluated the long-term outcome of 148 patients with small cell lung cancer (SCLC) who had been entered into clinical trials of chemotherapy with or without thoracic and prophylactic cranial irradiation (PCI) between 1981 and 1987. Eighteen patients (12%) survived for 2 or more years. With a minimum follow-up of 4.5 years, 10 of the 18 patients who remained disease-free at 2 years are currently alive and free of SCLC. Seven of these 10 patients currently function as they did before diagnosis. However, three suffer from central nervous system changes of varying degrees in severity which appeared 2-3 years after PCI. Eight of the 18 patients who were disease-free at 2 years have died. Two died of isolated relapse in the brain at 3.6 and 4.2 years after initiation of chemotherapy. Five died of other malignancies while continuing their complete response to SCLC; two of non-small cell lung cancer, two of acute myelogenous leukemia, and one of hepatocellular carcinoma. Another patient died of an unrelated disease without any evidence of SCLC. A small but substantial proportion of patients who underwent intensive treatment will achieve long-term survival; however, these patients remain at higher risk for second cancers and late toxicities. Therefore, attention must be directed to defining the safest way to employ such treatment in the management of SCLC.

In an attempt to elucidate the tumor properties relating to responsiveness to chemotherapy, we examined immunohistochemically the expression of P-glycoprotein (P-gp) and carcinoembryonic antigen (CEA) in small cell lung cancer (SCLC) tumors. Tumor specimens from 33 patients were obtained at the time of diagnosis and relapse. Four patients expressed P-gp in their initial tumors, and 7 others did in recurrent tumors. The overall response rate to chemotherapy of the initial tumors was 75% for P-gp-positive initial tumors and 86% for P-gp-negative tumors, whereas the disease-free and overall survival times were significantly shorter in the former than the latter. Three patients showed CEA in their initial tumors, and 5 others did in recurrent tumors. The patients with CEA-positive initial tumors tended to relapse earlier than those with CEA-negative tumors. In addition, recurrent tumors expressing CEA were resistant to salvage chemotherapy. A clear correlation between CEA expression by tumors and the CEA level in the serum was observed at diagnosis as well as at relapse. These findings indicate that P-gp and/or CEA expression by a tumor and elevated CEA level in the serum may predict refractoriness of the tumor to chemotherapy.

To improve the lymphokine-activated killer (LAK) cell therapy for liver metastasis, two methods which enhance accumulation of LAK cells in the liver were examined for their effects on the liver metastasis of Colon 26 cancer cells in BALB/c mice. Distribution of LAK cells in the mice was examined by the 51Cr labeling method. Portal vein infusion of LAK cells or tail vein infusion of neuraminidase treated-LAK (N-LAK) cells showed an augmented accumulation of infused cells in the liver. In the first experiment, LAK cells (5 x 10(7) cells) were infused in the portal vein or tail vein at days 3 and 7 after the inoculation of 5 x 10(4) tumor cells and 1 x 10(4) units of IL-2 were given three times a day from day 3 to day 7. The portal infusion of LAK cells produced a greater reduction of liver metastases compared with the peripheral infusion. In the second experiment, 5 x 10(7) LAK cells or N-LAK cells were infused via the tail vein on days 1 and 3, and 1 x 10(4) units of IL-2 were given once a day from day 1 to day 5 after the inoculation of 1 x 10(4) tumor cells. The therapeutic effect of N-LAK cells was greater than non-treated LAK cells on the number of metastatic lesions and the survival time of mice. Since access to the human portal vein is difficult and risky in clinical situation, peripheral infusion of N-LAK cells is preferable.