[Basic and clinical study of meropenem in pediatric field].

Meropenem (MEPM), a novel parenteral carbapenem antibiotic, was examined in a cooperative study involving 12 pediatric and 1 neonatologic facilities. The results are summarized as follows. 1. Antibacterial activity Antibacterial activity of MEPM against stock organisms including 31 strains of Streptococcus agalactiae, 14 of Listeria monocytogenes, 4 of Bordetella pertussis and 3 of Neisseria meningitidis ranged from 0.025 to 0.10 micrograms/ml in MIC90's, which were equal or lower than those of control drugs such as imipenem cefazolin, cefotiam, cefotaxime, ceftazidime and latamoxef. MICs against clinical isolates were as follows: In Gram-positive bacteria, MICs were 0.20 micrograms/ml to 6.25 micrograms/ml against 3 strains of Staphylococcus aureus, and 0.025 micrograms/ml or less against 4 of Streptococcus pneumoniae. In Gram-negative bacilli, MICs were 0.10 micrograms/ml to 0.20 micrograms/ml against 3 strains of Haemophilus influenzae and 0.78, 0.10 and 0.78 micrograms/ml, respectively, against one strain each of Enterobacter cloacae, Morganella morganii and Pseudomonas aeruginosa. MIC against 1 strain of Peptococcus saccharolyticus was < or = 0.025 micrograms/ml. 2. Pharmacokinetics Maximum plasma concentrations after intravenous infusion of MEPM over 30 minutes at doses of 10, 20 and 40 mg/kg, respectively, to 3 different groups of 3 children (total 9 cases) were observed at the completion of the treatment. Mean maximum concentrations in the 3 groups were 36.3, 69.5 and 129.8 micrograms/ml, respectively, exhibiting clear dose response. Mean plasma half lives in beta phase were 0.94, 0.86 and 0.94 hours, respectively, exhibiting no difference by doses, and this trend was observed also by HPLC. Urinary excretion rates in the first 6 hours after dose in the 10, 20 and 40 mg/kg groups were 67.3, 65.6 and 68.4%, respectively. Concentrations of MEPM in cerebrospinal fluid were determined in 2 cases of pyogenic meningitis. In 1 case, 500 mg (5.9 mg/kg) of MEPM was infused intravenously over 30 minutes and concentrations on Days 6, 8 and 15 observed at 190, 60 and 100 minutes after respective doses were 0.13, 0.10 micrograms/ml and less than the detection limit. Cerebrospinal fluid-plasma concentration ratio was determinable only on Day 8 and was 2.8%. In another case to which 250 mg (38.5 mg/kg) of MEPM was infused intravenously over 30 minutes, the concentration at Days 6, 7 and 10, 1 hour after the dose were less than the detection limit on day 6, and 2.04 and 2.62 micrograms/ml, respectively on days 7 and 10. 3. Clinical efficacy Clinical efficacies were evaluated in 49 cases and the efficacy rate was 93.9%.(ABSTRACT TRUNCATED AT 400 WORDS)


[Effect of meropenem on fecal flora in children].

Meropenem (MEPM, SM-7338), a novel parenteral carbapenem antibiotic, was examined for its effect on intestinal flora in children. Seven children with infectious diseases (3 male and 4 female children of age's ranging from 4 months to 8 years and 9 months weighing from 7.3 to 23.0 kg) were treated with MEPM at doses ranging 10.3 to 40.5 mg/kg 3 or 4 times a day for 6 to 12 days. Before, during and after the treatment, identities and numbers of various bacteria contained in 1 g of feces were determined and fecal beta-lactamase activity and Clostridium difficile D-1 antigen were also assayed. Changes in fecal flora during MEPM treatment was somewhat different depending on cases. Regarding Enterobacteriaceae among aerobes, all of 7 cases exhibited moderate or pronounced reductions in Escherichia coli. Some of the cases exhibited the tendency to increase in Klebsiella oxytoca. Enterobacter cloacae and Citrobacter freundii. E. coli which was reduced during the treatment increased rapidly after the treatment in 5 out of 7 cases, and the initial bacterial counts were restored. Diverse strains were observed within the genus Enterococcus, while the overall bacterial counts of this genus exhibited the tendency to increase during the treatment. As a result, no significant change in total aerobe count was observed in any case except 1 case where Enterococcus count was somewhat reduced. Among anaerobes, major bacteria such as Bacteroides, Bifidobacterium, Eubacterium and Peptococcaceae exhibited tendencies to decrease in some cases during the antibiotic treatment. Two infants and 1 child exhibited significant decreases in total anaerobe counts. In most of the cases, such changes in major anaerobes were transient and bacterial counts recovered to their initial values rapidly after completion of the treatment. In no cases, glucose non-fermentative Gram-negative bacilli or fungus became predominant. Although C. difficile D-1 antigen was observed in 4 cases, its changes had no relationship with characteristics of feces. C. difficile was not detected in any of the cases. MEPM was detected in feces in 4 cases being treatment, in concentrations ranging from 0.35 to 66.0 micrograms/g. Fecal MEPM levels were very low except in 1 case in which beta-lactamase was negative. From these results, effects of MEPM on intestinal flora in children were relatively minor compared to other new beta-lactam drugs. However, a care should be taken to minimize diarrhea and bacterial turnover when a prolonged use of the antibiotic, was practiced because of potential significant effects on intestinal flora.


[Laboratory and clinical evaluation of meropenem in pediatric field].

We performed laboratory and clinical evaluation of meropenem (SM-7338, MEPM), a new carbapenem antibiotics, in pediatric field. Pharmacokinetics of MEPM was examined with 5 patients, at a dose of 10 mg/kg via 30 minutes drip infusion. Mean plasma concentrations at 30 minutes, 1, 1.5, 2.5, 3.5 and 5.5 hours after dose were 18.8, 6.97, 3.62, 1.14, 0.43 and 0.12 micrograms/ml, respectively, with a half life of 0.96 hour. The urine recovery rate in 6 hours was 70.4%. Clinical efficacy of MEPM was evaluated in 36 patients with various infectious diseases. MEPM was administered at doses ranging 9.5 to 30.6 mg/kg/dosage, 3 to 4 times a day, 21/3 to 10 days. Clinical effects were excellent in 24, good in 11, fair in 1, with an efficacy rate of 97.2%. Bacteriologically, all causative organisms except one each of Haemophilus influenzae and Salmonella enteritidis were eradicated, an eradication rate for Gram-positive and Gram-negative bacteria were 100% and 93.3%, respectively. No side effects were observed. Elevations of GOT and/or GPT were noted in 2 patients. From the above results, we believe that MEPM is a highly effective and safe drug for patients with various infectious diseases in pediatric fields.


[Plasma interleukin-6 in patients with disseminated intravascular coagulation].

Plasma Interleukin-6 (IL-6) level was measured in 60 patients with disseminated intravascular coagulation (DIC). Plasma IL-6 level was high in patients with DIC, and was particularly high in patients with multiple organ failure (MOF) or poor prognosis. Plasma IL-6 level correlated positively with C-reactive protein in patients without DIC, but not in those with DIC. The increased plasma IL-6 level observed in DIC patients suggests that activation of the immune system is involved in the progression of DIC and in the pathology of organ failure.


[Benefits and problems of home infusion therapy].

A survey was performed to clarify the benefits and problems of home infusion therapy because 8 years had passed since this type of treatment was officially approved in Japan. Questionnaires were sent to hemophiliacs and the physicians in charge of hemophiliacs in the Kyushu district. The main results obtained from analysis of responses concerning 197 patients were as follows. 1) Out of 197, 140 patients were on home therapy programs. 2) The number of bleeding episodes was increased in 6.8%, decreased in 51.1% and unchanged in 42.1% of patients after the start of home infusion therapy programs. 3) The severity of bleeding symptoms was reduced in 92.9% of patients after the start of these programs. 4) After the start of home infusion therapy programs, the amount of blood products administered increased in 24.4%, decreased in 20.6% and was unchanged in 55.0%. 5) Complications such as abdominal pain, headache, ulticaria, itching, shivering, fever and discomfort were reported from 19 hemophiliacs. Only one of them visited the hospital due to severe abdominal pain which appeared immediately after home infusion of blood product. 6) It was indicated that better education or re-education of home infusion therapy is necessary for hemophiliacs and/or their families who are on home infusion therapy programs, because half of them had not received proper education concerning home infusion.


[Rapid disappearance of M-protein in multiple myeloma complicated by pneumonia during treatment with HLBI].

A 64-year-old female was admitted for treatment of refractory myeloma (IgG-lambda). Because of severe liver cirrhosis, the patient was treated with interferon (IFN) alone (natural IFN 6 x 10(6) IR/day i.m. for 28 days). Pneumonia developed during IFN therapy. The IFN therapy was completed, restoring suppressed IgM and IgA to their normal ranges, while pneumonia was cured by antibiotics. Because the M-component remained, an additional IFN therapy was resumed and M-protein disappeared. As the period within which the M-component disappeared in this case was shorter than that reported previously, we supposed that the pneumonia might have enhance the effects of IFN. To verify this, we administered OK-432 for 4 weeks as a model of immunoactivation by pneumonia between two successive courses of IFN therapy when M-protein reappeared. To monitor the immune state, natural killer (NK) and lymphokine activated killer (LAK) activities were measured: NK activity suppressed by IFN was restored by OK-432 and was suppressed less by subsequent IFN administration. LAK activity was increased by IFN and OK-432. These observations suggested synergic effects of OK-432 on IFN-activated immunity. This case suggests that IFN combined with immunotherapy may be effective in some cases of myeloma.


[Reactive histiocytosis during initial remission induction therapy for acute myeloblastic leukemia].

Six of 14 patients with acute myeloblastic leukemia (AML) complicated reactive histiocytosis during initial remission induction therapy. All six patients had a high fever without signs of infection during initial chemotherapy, and periods of myelosuppression were prolonged. Histiocytes with a mature appearance, some of which phagocyted erythrocytes, thrombocytes or neutrophils, increased in the bone marrow. All of 3 patients tested showed high serum levels of ferritin. Two of 3 patients treated with 125 mg/day methylprednisolone achieved complete remission. In the remaining 3 patients, one patient achieved complete remission, but the others died of fungal pneumonia or sepsis. Thus, reactive histiocytosis is one of the severe complications in patients with AML undergoing chemotherapy.


[der(1;7) (q10;p10) in three patients with malignant hematologic disorders].

The chromosome der(1;7) (q10;p10) is a derivative chromosome consisting of the short arm of chromosome 7 and the long arm of chromosome 1. We observed this abnormality in three patients with acute myeloblastic leukemia (AML), myelodysplastic syndrome (MDS), or myeloproliferative disorder (MPD). Case 1 was a 76-yr-old male with a history of IgG myeloma treated with melphalan, cyclophosphamide, vincristine, and prednisolone (MEVP). AML-M1 developed one and half years after discontinuation of the MEVP therapy. Case 2 was a 39-yr-old male with MDS. Case 3 was a 56-yr-old male with refractory anemia with excess of blasts in transformation that evolved from primary myelofibrosis. Chromosome analyses revealed der(1;7) (q10;p10) in bone marrow cells of the three patients. All patients failed to respond to chemotherapy, and died within four months after the diagnosis. Thus, der (1;7) (q10;p10) may indicate a very poor prognostic outcome in patients with malignant hematologic disorders.


[Burkitt's lymphoma diagnosed by molecular analysis of DNA from malignant cells in ascites].

A 73-year-old man was admitted with severe abdominal fullness. Physical examination suggested much ascites. Laboratory data revealed that BUN was 39 mg/dl, Cr was 2.2 mg/dl, UA was 19.7 mg/dl, and LDH was 1,569 U/l. In ascites, there were many cells with large nuclei and many vacuoles. Immunocytological characterization indicated that most of these cells were B lineage. And diagnosis of malignant lymphoma, the patient was treated with VEPA therapy. However, he soon died with acute renal failure. We examined the possibility of gene rearrangements between the c-myc and immunoglobulin genes and found that c-myc gene was rearranged at the first intron, and joined with immunoglobulin JH locus as head to head. These results suggested that the patient carried Burkitt's lymphoma of the American type.


[Malignant histiocytosis with T cell receptor and immunoglobulin gene rearrangements].

A case of malignant histiocytosis with rearrangements of both T-cell receptor and immunoglobulin genes. The patient was a 69 year-old woman suffering from high fever, which was unresponsive to the administration of various antibiotics and steroids for more than two weeks. Laboratory findings on admission revealed disseminated intravascular coagulopathy and liver dysfunction. The bone marrow examination showed an increased number of giant cells. Some of the giant cells had phagocytosis of various blood cells and were cytochemically stained with non-specific esterase, but not with myeloperoxidase and PAS. Immunohistochemical study revealed that alpha 1-antitrypsin alpha 1-antichymotrypsin, lysozyme and CD15 were all detected in the cytoplasm of some giant cells while CD30 was not detected. Of interest was the rearrangements of the T-cell receptor, Ig heavy chain and kappa chain genes on bone marrow mononuclear cells demonstrated by Southern blot analysis.


[Infiltration into the aqueous humor (uveitis) in a patient with malignant lymphoma].

An 80-year-old male was admitted to our hospital because of multiple tumors in October 1989. A pathological diagnosis of non-Hodgkin's lymphoma (diffuse, medium-sized cell type) was made with the histological examination of his biopsied tumors. His clinical stage was stage IV A. Chemotherapy (CHOP) brought him to complete remission. In May 1990, relapse of non-Hodgkin's lymphoma was observed in the neck and both eyes. The diagnosis of uveitis due to involvement of lymphoma cells was confirmed by an aspiration biopsy of left aqueous humor. Complete recovery of his visual acuity was possible with additional chemotherapy, and lymphoma cells in his right aqueous humor were expelled completely, while his cervical tumor remained 1/3 of the original size. He eventually died of pneumonia on December 9th, 1990. Intraocular involvement of malignant lymphoma is rare in comparison with extraocular involvement. Especially, the patient who has only turbid aqueous humor as an ophthalmic sign is very rare. In this paper, we reported a case of lymphoma with intraocular involvement and discussed the mechanisms of infiltration of lymphoma cells into the aqueous humor and the therapy.


[Megakaryoblastic leukemia which developed from therapy-related MDS with myelofibrosis].

A 56-year-old man had a leiomyosarcoma of the small intestine in 1987. After surgery, he received cyclophosphamide for 2 years. In December, 1990, he exhibited severe pancytopenia. His hematological data were as follows: Hb 7.4g/dl, ret. 0.8%, WBC 1,700/microliters with leukoerythroblastosis and 2.8 x 10(4)/microliters platelets. A bone marrow aspiration was a dry tap. A bone marrow biopsy specimen showed a hypercellular marrow with myelofibrosis, leukemic infiltration (10.2%) and slight dyserythropoiesis. Both PPO and GPIIb/IIIa reaction were positive for blast cells and atypical megakaryoblasts. A diagnosis of MDS with an abnormality in megakaryocytic lineage was made. The patient was treated with 1,25-dihydroxy-vitamin D3, however this therapy was temporary and he developed into acute megakaryoblastic leukemia (M7). This report suggested that some cases of therapy-related leukemia (TRL) mainly involve megakaryocytic lineage and are diagnosed as MDS with myelofibrosis which transform to M7. The fact that PAS stain of erythroblasts in the patient reported here was positive may suggest involvement of development of more precise immunological markers of differentiation and EM study will permit better diagnosis of TRL and may therefore facilitate new therapeutic approaches.


[Rapid aggravation of splenomegaly by administration of erythropoietin in a case of myelodysplastic syndrome].

In myeloproliferative disorders, aggravation of splenomegaly was reported as an adverse effect of erythropoietin (EPO). Recently, we experienced the adverse effect of EPO in myelodysplastic syndrome (MDS). A 65-year-old male was admitted to our hospital for scrutiny of pancytopenia in July 8, 1991. He was diagnosed as having MDS (refractory anemia: RA). After discharge, daily subcutaneous administration of EPO (3,000U) was started on August 1 because his Hb concentration had decreased to 9.2 g/dl. After the daily dose of EPO was increased up to 6,000U in August 15, left hypochondralgia gradually developed. EPO administration was haltedon August 22. His splenomegaly was aggravated from 2 finger breadths below the left costal margin before EPO administration to 4.5 finger breadths. Bone marrow examination revealed a change to extremely hypercellular marrow from slightly hypocellular marrow before EPO administration. The peripheral blood cell count was not altered. We concluded that he was a rare case of MDS in which aggravation of splenomegaly was observed, probably as a result of extramedullary hematopoiesis induced by administration of EPO.


[Polycythemia vera terminating in chronic neutrophilic leukemia: studies on in vitro growth of hematopoietic progenitor cells].

A 57-year-old man, diagnosed as Polycythemia vera (PV), had been treated with administrations of Busulfan since 1984. Three years later, the number of neutrophils in peripheral blood increased to 50,000/microliters with progression of splenomegaly, and the case was diagnosed as Chronic neutrophilic leukemia (CNL) based on the criteria by Miura et al, in November, 1989. In spite of 6MP and Busulfan therapy, marked neutrophilia and splenomegaly progressed, and the patient died due to liver dysfunction in June of 1991. To clarify the pathophysiology of PV and CNL, we studied the in vitro growth kinetics of hematopoietic progenitor cells in bone marrow of this unique case and made a comparison with those of 4 cases of PV and 4 normal volunteers employing methylcellulose culture. As in other cases of PV, erythroid colonies were formed in culture of bone marrow from this patient without addition of erythropoietin. Furthermore, spontaneous colonies derived from CFU-GM and CFU-Mix increased remarkably in this case only. The results suggest that the hematopoietic abnormalities in this case involve the multipotent stem cells as well as erythroid and granuloid-macrophage progenitors.


[A case report of an acute promyelocytic leukemia patient showing remarkable thrombopoiesis prior to granulopoiesis by hM-CSF treatment after chemotherapy].

We report a case of an acute promyelocytic leukemia patient who showed remarkable thrombopoiesis prior to granulopoiesis by human macrophage colony-stimulating factor (hM-CSF) treatment after chemotherapy. A 50 year-old man was diagnosed as acute promyelocytic leukemia (FAB classification: M3) with t(15;17). He received two courses of induction therapy with daunorubicin and cytarabine followed by consolidation therapy with cytarabine and mitoxantrone. After each course of chemotherapy. hM-CSF (8 x 10(6) units, daily) was given for 14 days. After each treatment with hM-CSF, the increase in number of platelets preceded increase of granulocytes and reticulocytes. When serum levels of granulocyte-macrophage-colony stimulating factor (GM-CSF), granulocyte-colony simulating factor (G-CSF), interleukins-3 (IL-3) and -6 (IL-6) were measured, only that of G-CSF was increased after hM-CSF treatment.


[Induction therapy of acute promyelocytic leukemia with all-trans retinoic acid: a case, followed by conventional post-remission chemotherapy in complete remission].

A 41-year-old man with untreated acute promyelocytic leukemia (APL) was treated with all-trans retinoic acid (ATRA) 80mg/body/day per os. Complete remission was reached in 16 day without bone marrow hypoplasia and aggravated disseminated intravascular coagulation. The chromosomal abnormality, t (15;17), which presented before therapy has not been found since the 29th day of therapy. During the course of induction therapy with ATRA, there was no complication worth of mentioning. Induction therapy with ATRA is thought to be more effective and safer than conventional chemotherapy to attain complete remission in APL. The complete remission has been maintained for 11 months with conventional postremission chemotherapy.


[Eosinophilic leukemia with cyclic eosinophilic leukocytosis].

A 36-year-old male was admitted to the Ehime University Hospital with anemia, eosinophilia and hepatosplenomegaly. Peripheral blood examination demonstrated severe anemia (Hb 7.1g/dl), thrombocytopenia (Plt 6.8 x 10(4)/microliters) and increase of peripheral leukocyte counts (53,000/microliters) with 32.0% of eosinophils which had lobulated nuclei, abnormal distribution of eosinophilic granules and a few vacuoles. The level of serum IgE was low (< 5IU/ml), while that of serum vitamin B12 was elevated. A diagnosis of eosinophilic leukemia was made. He was noted to have spontaneous fluctuations in his eosinophil and total leukocyte counts. To analyze the mechanism of cyclic eosinophilic leukocytosis, we examined eosinophil colony stimulating activity of the serum and plasma of the patient. These examination showed that eosinophil colony-stimulating activity was not found in his serum and plasma, and cyclic eosinophilic leukocytosis was due to the hemopoietic stem cell disorder.


[Chronic myelomonocytic leukemia with good response to low-dose etoposide].

58-year-old man was admitted with cervical tumor and leukocytosis. Physical examination indicated splenomegaly and cervical abscess. Laboratory data showed WBC 55,000/microliters, Hb 7.9g/dl, and PLT 4.5 x 10(4)/microliters. After cure of the abscess, WBC counts were still high with 1,500-2,000/microliters monocytes, and anemia and thrombocytopenia persisted. Bone marrow aspiration showed myeloid hyperplasia and trilineage myelodysplasia. The Ph1 chromosome could not be detected. The case was diagnosed as chronic myelomonocytic leukemia and treated with oral etoposide (25mg/day). After 2 weeks, the dose was increased to 50mg, and then modified according to the blood counts. WBC counts are presently being maintained between 7,000 and 12,000/microliters, and RBC and PLT counts have gradually become normal. Splenomegaly almost disappeared and dysplastic change in bone marrow improved somewhat. At nine months following the start of chemotherapy with etoposide, remission is maintained by treatment with 25mg of etoposide on alternate days. This case suggests that low-dose etoposide is useful for treating CMMoL.


[Clinicopathological study on the relationship between appearance of type I or III collagen in IgA nephropathy].

This study was designed to determine whether or not the appearance of type I or type III collagen in glomeruli and serum procollagen III peptide (PIIIP) concentration are affecting the prognosis of patients with IgA nephropathy. In cases with reduced creatinine clearance (Ccr < 80 ml/min) at the time of renal biopsy, the appearance of type III collagen increased, and subsequently type I collagen appeared as Ccr decreased. In addition, we measured serum PIIIP concentration in these cases. The increase of serum PIIIP correlated with the decrease of Ccr. These results suggest that the appearance of type I and III collagen in glomeruli and the increase in serum PIIIP concentration might be a useful marker to predict the outcome of IgA nephropathy.


[Steroid pulse therapy in rapidly progressive glomerulonephritis].

In an attempt to clarify the indication and efficacy of the methylprednisolone pulse therapy (1000 mg x 3 times) for rapidly progressive glomerulonephritis (RPGN), 3 patients with the disease were carefully followed and the clinical course during and after the treatment were precisely analysed. According to the declination rate of reciprocals of serum creatinine (1/Cr), one patient were divided into the acute type (-1.00 x 10(-2) dl/mg/day or less) and the others into the subacute type (more than -1.00 x 10(-2) dl/mg/day). In the patient of acute type, renal biopsy revealed cellular crescent formation in 93.8% of glomeruli observed. One course of the pulse therapy resulted in a decrease in Cr from 3.0 mg/dl to 1.3 mg/dl and transformation of cellular crescents to fibrocellular or fibrous crescents. In the other two patients of subacute type, crescents were observed in 72.7% and 72.0% of glomeruli observed, and 87.5% and 38.9% of them were composed of cellular crescents respectively. Initial courses of the pulse therapy resulted in decreases of Cr from 3.5 mg/dl to 2.4 mg/dl and from 3.0 mg/dl to 1.4 mg/dl respectively. Additional courses, given because of insufficient reduction of Cr in the former, induced a further lowering to 1.3 mg/dl, and because of re-elevation of Cr to 2.2 mg/dl and remaining of cellular crescents in 20% in the latter, induced a decrease of Cr to 1.5 mg/dl and disappearance of cellular crescents.(ABSTRACT TRUNCATED AT 250 WORDS)


[Alterations in phosphatidylcholine and phospholipase A2 of the renal tissue in gentamicin nephrotoxicity: comparative study with buthionine sulfoximine administered model].

We investigated to confirm the biochemical mechanisms of the hypothesis that lipid peroxidation participates in the pathogenesis of aminoglycoside-induced nephrotoxicity. Male Sprague-Dawley rats were injected with gentamicin (GM), 300mg/kg per day. Twenty-four hours after the injection the rats were killed and the renal cortex was processed for glutathione (GSH), malondialdehyde (MDA), phospholipase A2 (PLA2), phosphatidylcholine (PC), sphingomyelin (SPH) and phospholipids (PL). And we also studied the GSH reduced rats by buthionine sulfoximine (BSO) administration, to compare the biochemical differences with these parameters in two groups. GM induced a significant decrease of PLA2, SHP/PC ratio and GSH. Marked elevation of MDA (lipid peroxidation) and PC were observed after a single injection of GM. In contrast, BSO injected rats were not showed increment of tissue MDA, in spite of marked reduction of renal GSH. These data support the conclusion that accelerated lipid peroxidation occurs early in the course of GM administration and inhibition of lysosomal PLA2 activity involved in the degradation of lysosomal membrane which consisted of phospholipids.


[Inflammatory cell infiltration around beta 2-microglobulin amyloid deposition: histologic comparison of beta 2-microglobulin amyloidosis with AA or AL amyloidosis].

Thirty-one autopsy cases of beta 2-microglobulin (beta 2M) amyloidosis were pathologically investigated in comparison with 17 autopsy cases of AA or AL amyloidosis. In 20 cases (65%, 20/31) of beta 2M amyloidosis, inflammatory cells, mainly macrophages were seen infiltrating around beta 2M amyloid in intervertebral disks. The more beta 2M amyloidosis advances, the more macrophage infiltration tends to be prominent. In cases of severe beta 2M amyloidosis, the cytoplasm of macrophages around amyloid deposition were swollen with engulfed amyloid substance and were often transforming to foreign body multinucleated giant cells. In addition, granulation tissue was formed with infiltrating macrophages, foreign body multinucleated giant cells, capillary proliferation and fibrosis around beta 2M amyloid deposition. On the other hand, inflammatory cell infiltration around amyloid deposition was scarcely seen in AA or AL amyloidosis. Ultrastructurally, macrophages were abundant in phagocytic vacuoles containing amyloid fibrils. These macrophages were immunohistochemically positive for CD68, IL-1 beta and TNF-alpha. Thus, macrophage infiltration around beta 2M amyloid is thought to be responsible for local pain and tissue destruction of dialysis patients.


[Study of recombinant human erythropoietin treatment on the anemia of predialysis patients].

We conducted a multiple-center joint study on the effects of recombinant human erythropoietin (rEPO) for predialysis patients. rEPO was intravenously administered to 42 predialysis patients (13 males and 29 females) with hematocrit (Ht) levels of less than 30%. The subjects were divided into group A (28 cases) in which rEPO was administered twice a week, and group B (14 cases) with rEPO administration once a week. The initial administration dosage was 6000IU/week. The Ht levels were 22.6 +/- 3.3% for group A and 23.2 +/- 2.7% for group B before the administration of rEPO, and increased to 31.0 +/- 4.0% and 27.7 +/- 3.7% respectively twelve weeks after initiating administration. The levels of effective improvement on anemia included 'markedly effective' in 17 cases (80.9%) and 'effective' in 2 cases (9.5%) in group A, and 'markedly effective' in 5 cases (41.7%) and 'effective' in 3 cases (25.0%) in group B. No significant change was seen in serum creatinine (Cr) levels during the study period. In the evaluation of renal function by reciprocal serum creatinine (1/Cr), a consistent tendency was not recognized; thus, suggesting that the rEPO administration had no effect on the renal function. No variation of blood pressure was seen. As far as side effects were concerned, headache and heavy headedness were recognized in four cases. There were, however, no cases in which the severity of the side effects dictated the discontinuation of the rEPO administration. In conclusion, rEPO was judged to be a safe and effective treatment for the anemia of predialysis patients.


[Pharmacokinetics and clinical effect of recombinant human erythropoietin on the anemia of predialysis patients].

The marvelous effect of recombinant human erythropoietin (EPOCH) on the anemia of the patients suffering from chronic renal failure had been already reported even in the predialysis patients. However, the influence on residual renal function as well as pharmacokinetics of EPOCH in predialysis patients was not clarified yet. Therefore, we made a clinical study of EPOCH in 10 predialysis patients to investigate the clinical effect as well as pharmacokinetics. EPOCH was administered intravenously once a week with the dosage of 3,000-9,000 IU for 8 weeks. All patients showed prominent improvement of anemia. Though no patient show serious adverse effect, two patients showed controllable hypertension accompanying with the increase of hematocrit. Meanwhile, the speed of the deterioration of residual renal function obtained from the regression line by reciprocal of the serum creatinine was not aggravated by the correction of anemia. Pharmacokinetic study revealed that the halflife of EPOCH was extended compared to normal but the degree of extension was same as that of in dialyzed patients. The plasma concentration-time curves showed the pattern of monoexponential disappearance and the area under the curve (AUC 0 to 48 hr.) showed dose-response increase. However, both parameters mentioned above as well as systemic clearance rate did not show any change between those of on day 0 and on day 56. These results no long-term accumulation of EPOCH, though the level of intrinsic erythropoietin was decreased after EPOCH treatment. Thus, the beneficial effect of EPOCH on the correction of anemia was revealed even in the predialysis patients without affecting on residual renal function.


[Surgical exploration for renal cyst: two-case report].

A 59-year-old male was admitted to our clinic for further examination of the calcified renal cyst discovered incidentally on medical workup elsewhere. CT showed a left renal cyst associated with calcification. Ultrasound-guided puncture of the renal cyst was not successful because of thickness of the cystic wall. Renal angiography showed hypervascularity of the cystic wall. Association of renal cell carcinoma could not be ruled out, therefore the exploration was performed. Histological examination revealed benign renal cyst with calcification. A 27-year-old male presented with the chief complaint of left flank pain. Following examinations by US, CT and MRI, a renal cyst associated with renal cell carcinoma was highly suspected. Subsequent exploration revealed cluster of cysts with a yellowish lesion a few mm in diameter. Frozen section revealed no malignancy, and cystic fluid was not hemorrhagic. Therefore as many cystic walls as possible were removed without nephrectomy. Histological examination of the permanent specimen revealed renal cell carcinoma. Renal cyst associated with renal cell carcinoma was regarded as rare clinical entity, but such cases are reported in increasing number in recent years. We report such cases and review the pertinent literature in this paper.


[Successful treatment with steroid pulse therapy in a case of dilated cardiomyopathy associated with mesangial proliferative glomerulonephritis].

A 28-year old male was admitted to our hospital because of heart failure, chronic renal failure and nephrotic syndrome. Light microscopic findings of his kidney biopsy showed proliferation of mesangial cell and marked narrowing the lumina of small arteries and arterioles. The changes of these small vessels were not those of typical vasculitis, when we considered his age and his past history. The diagnosis of dilated cardiomyopathy was made by the findings in echocardiography and cardiac catheterization. Since the heart failure and renal disease seemed to be simultaneous initiated, it was supposed that the diseases in two organs were caused by a common pathogenesis related to that of vasculitis. When steroid pulse therapy was adopted, both of cardiac and renal function responded to this treatment (ejection fraction from 26% to 52%, creatinine clearance from 48 to 62 ml/min). Increase of CD56 positive cells (natural killer cells) in peripheral blood was ameliorated after the treatment. These findings suggest that cellular immunity may be concerned with the pathogenesis of the combination of dilated cardiomyopathy and renal disease in this case.


[A case of primary amyloidosis associated with giant cell infiltration within a Bowman's capsule].

A 67-year-old man was hospitalized with a diagnosis of nephrotic syndrome. Physical findings at admission were generalized edema and macroglossia. Urinalysis showed massive proteinuria, + +occult blood, and granular and broad casts. Ig A lambda monoclonal gammopathy was noted in the serum. There was no evidence of myeloma in the bone marrow aspirate, scintigram or X-ray of the bone. A biopsy specimen of the kidney showed massive deposits of structureless material in the glomeruli. Marked cell infiltration was also observed in the interstitium. Multinucleated giant cells were occasionally seen in the Bowman's capsules and the interstitium. There were reactive changes in the Bowman's capsule adjacent to the giant cell. The deposits were proved to be amyloid by positive staining with Congo red and apple-green birefringence by polarized light. In addition, microfibrills seen on electron microscopy displayed deposits. Amyloid depositions were observed in other tissues such as gingiva, skin and tongue. Staining of amyloid with Congo red was resistant to potassium permanganate, and amyloid was positively stained with lambda-light chain of immunoglobulin. These findings indicated that the patient had primary amyloidosis. Infiltration of the multinucleated giant cell has been reported only in patients with familial amyloidosis and secondary amyloidosis associated with rheumatoid arthritis. To our knowledge the present case is a first report of the giant cell infiltration in a Bowman's capsule in primary amyloidosis.


[Effects of intravenously infused magnesium on renal calcium metabolism and plasma parathyroid hormone in patients with essential hypertension].

This study aimed to elucidate the effects of intravenously infused magnesium on renal calcium and sodium metabolism in patients with essential hypertension. Mean arterial pressure (MAP), heart rate (HR), urine volume (UV), endogenous creatinine clearance (Ccr), urinary excretion of calcium (UCaV) and sodium (UNaV), fractional excretion of calcium (FECa) and sodium (FENa), plasma ionized calcium (pCa2+) and parathyroid hormone(PTH) were measured before and after intravenous infusion of 10% magnesium sulfate (initial dose: Mg 13.5mg/m2.BSA/15 min.: maintenance dose: Mg 2.7mg/m2.BSA/105min) in 6 normotensive subjects (NT) and 13 mild-to-moderate essential hypertensives (EHT). After the magnesium infusion, significant increases of UV, UCaV, UNaV, FECa and FENa, and a significant decrease of PTH were observed in both NT and EHT while MAP and HR did not change in either group. PCa2+ significantly decreased and Ccr tended to increase only in EHT. Although no significant difference was found in the change in Ccr (delta Ccr) or PTH (delta PTH) between NT and EHT, the changes of UCaV (delta UCaV), UNaV (delta UNaV), FECa (delta FECa) and FENa (delta FENa) were greater in EHT than each in NT. A positive correlation was found between delta UCaV and delta FECa, as well as delta UCaV and delta Ccr, but the former was more remarkable in both groups. In addition, delta UCaV was positively correlated with delta FENa in EHT, but not in NT. No significant relationship was observed between delta UCaV and delta PTH in either group.(ABSTRACT TRUNCATED AT 250 WORDS)


[Production of reactive oxygen species and scavenger treatment in nephrotoxic nephritis].

Role of reactive oxygen species (ROS) was studied in accelerated nephrotoxic nephritis (NTN) in rats. In this experimental model, histological examination, and luminol amplified chemiluminescence (CL) assay of peripheral polymorphonuclear neutrophils (PMN), peritoneal macrophages (M phi), and isolated glomeruli were performed time-sequentially. Effect of ROS scavengers were also examined in this experiment. Daily dosages of bovine liver catalase and SOD were 550,000 and 1,000 units respectively. After nephrotoxic IgG injection, CL of glomeruli increased strikingly attaining peak at day 1, and remained high until the end of the experiment. This increase of CL may have reflected the release of ROS by glomerular cells and/or infiltrating cells stimulated in situ. In fact, peripheral PMN and peritoneal M phi showed no increase of CL after nephrotoxic IgG injection. Glomerular cells increased as early as 3 hours after induction of nephritis. Accumulation of PMN was noted for the first three days, whereas that of M phi became prominent after 4 days. Favourable effect was obtained in terms of proteinuria by administration of catalase, only when catalase was given at initial 3 days of nephritis. The data suggest that generation of ROS reflected by increase of CL in glomeruli of NTN rats is attributable to the PMN and M phi infiltrated in glomeruli as well as glomerular resident cells per se. It is also suggested that glomerular PMN increasing in the early phase of NTN plays a considerable role in glomerular injury.


[Clinicopathological survey of persistent hypocomplementemic glomerulonephritis in children; correlation of DPGN and MPGN type I].

We studied clinicopathologically 19 patients with abnormal urinary findings accompanying with persistent hypocomplementemia under age 15. They consisted of 6 patients with membranoproliferative glomerulonephritis (MPGN) type I, 2 with MPGN type II, 2 with focal MPGN, 8 with diffuse proliferative glomerulonephritis (DPGN), 1 with focal glomerulonephritis (FGN). 17 cases were treated with steroid. In 2 patients with MPGN type I and 1 patient with DPGN, the treatment resulted in normalization of serum C3 level and urinary abnormalities and improvement of histological findings. In 3 patients with DPGN, urinary abnormalities and hypocomplementemia have been persisted and histological findings changed to those of MPGN type I. Thus, DPGN with hypocomplementemia seems to be an early stage of MPGN type I.


[The effect of elastase on aminonucleoside nephrosis--on renal vascular system].

This study was performed to investigated the relationship between cross sectional areas of glomerular arterioles and glomerular volume in rats with puromycin aminonucleoside (PAN)-induced nephrosis, which is an experimental model of glomerular sclerosis. We also evaluated the effect of an anti-arteriosclerotic agent, elastase on these parameters. Six-week-old male Sprague-Dawley rats were divided into 3 groups; control, PAN-treated (70 mg/kg i.p.), or PAN+elastase-treated (5 mg/kg/day i. m.) group. After 12 weeks of experimental period, microvascular cast of the kidney was prepared, and the cross sectional areas of afferent and efferent arterioles as well as glomerular volume were measured using scanning electron microscopy. In the juxtamedullary glomeruli with minor abnormalities, the efferent arteriole was narrower in PAN-treated rats than in the control rats and the elastase-treatment partially corrected it (control 55.7, PAN 35.9, PAN+elastase 43.7 x 10 microns 2). On the other hand, the cross sectional area of afferent arteriole was not different among the 3 groups. In glomeruli showing sclerosis, the cross sectional area of efferent arteriole correlated positively with the glomerular volume. There results suggest that constriction of the efferent arterioles contributes to the development of glomerular sclerosis in PAN-induced nephrosis. In addition, elastase possibly inhibits this process and thereby protect glomeruli from sclerosis.


[Complications of percutaneous renal biopsy].

Three hundreds percutaneous renal biopsy cases were analyzed for recorded clinical complications retrospectively. Incidence of fever (> or = 37.5 degrees C), pain, and decrease in hematocrit (> or = 4%) was 21%, 28%, and 13% respectively. The incidence of fever and pain were less in the older patients. Prospectively, 125 cases who underwent ultrasonography following renal biopsies and 62 cases who underwent computerized tomography were analyzed. Bigger hematoma was followed by fever 5-7 days after renal biopsies. Incidence of pain and the decrease in hematocrit were correlated with the size of hematoma. Use of the ultrasonographic localization and a Tru-Cut biopsy needle or a Biopty-Cut needle decreased the incidence of hematoma more than 50ml following renal biopsy (0-5%). Incidence of fever and pain was less by these new procedure. The risk of hematoma increased as the biopsy needle went deeper into medulla.


[Clinical investigation of cis-platinum nephrotoxicity in 244 cases of primary lung cancer].

Cisplatin (CDDP) is used widely in the treatment of a large number of carcinomas. The clinical use of cisplatin, however, can be complicated by myelotoxicity, intestinal toxicity and nephrotoxicity. We reviewed CDDP nephrotoxicity in 244 cases with primary lung cancer retrospectively. The enzyme histochemically localized in proximal tubular cells, N-acetyl-beta-D-glucosaminidase (NAG) and beta 2-microglobulin (BMG), a low molecular weight peptide normally reabsorbed by the renal tubular cells that has been used as an indicator for renal proximal tubular damage, were measured. And fractional excretion of Na (FENa%) and serum magnesium (Mg) levels were also measured before and after CDDP administration serially. The following results were obtained; 1) Over 45% of patients with lung cancer showed transient hyperexcretion of urinary NAG and BMG after CDDP administration. And peak excretion of NAG and BMG appeared to occur within 36 hours after administration of CDDP. 2) Almost all cases with persistent azotemia after CDDP administration showed high values of FENa (%), in spite of gradual normalization of urinary NAG and BMG excretion. 3) Hypomagnesemia was a common complication of CDDP nephrotoxicity that might be caused by a defect in renal Mg reabsorption. CDDP-induced nephrotoxicity seemed to be initiated by an acute, mainly proximal tubular impairment that reflects alterations in excretion of urinary enzymes and low molecular weight protein. In cases with persistent azotemia after CDDP administration depressed renal function might be attributed to the impairment of proximal as well as distal tubular reabsorptive functions.


[The oral 1-25 dihydroxyvitamin D3 pulse therapy in hemodialysis patients for the early treatment of secondary hyperparathyroidism].

It is said that maintenance hemodialysis patients are already suffering from secondary hyperparathyroidism (2HPT) from early stage of chronic renal failure. The treatment of 2HPT in this stage is very important for preventing renal osteodystrophy (ROD). But many long-term dialysis patients are still afflicted with ROD although vitamin D have been used for treatment. In this study, an oral administration of 1-25 (OH)2 D3 (4 micrograms) with pulse therapy twice a week at the day before hemodialysis was started for 12 weeks. The concentration of 1-25 (OH)2D3, total calcium (Ca), ionized calcium (Ca++), alkaline phosphatase (ALP) and parathyroid hormone (PHT) in serum were measured not only before and after every 2 hours of administration a day, but also for 12 weeks after that. The peak of serum 1-25 (OH)2D3 could be sufficiently elevated after 8 hours, and the slight peak of Ca++ could be seen after 8 hours as well. But the level of total calcium could not increased. Although the level of only HS-PTH has not increased after 24 hours, a significant reduction in serum level of C-PTH, intact-PTH and HS-PTH could be recognized after 12 weeks finally. This pulse therapy was effective in reducing the serum level of PTH in this early stage from beginning hemodialysis. But, it needs further studies for the standard treatment.


[Adequate Ca level for dialysis patient (study on medical therapy for secondary hyperparathyroidism in dialysis patient)].

We evaluated our medical therapy of secondary hyperparathyroidism (2 degrees HPT) in dialysis patients. Ten hemodialysis patients with 2 degrees HPT (PTH-C; higher than 10ng/ml) were treated with vitamin D3, large amounts of phosphate binders and calcitonin and data over three years were examined. Our data showed that 2 degrees HPT is manageable by medical therapy. Furthermore, we suggest that the adequate Ca level for dialysis patients is to maintain the Ca (mEq/1) xP (mg/dl) at less than = 35. When plasma P is less than 6mg/dl. The maintenance of this Ca level successfully treated 2 degrees HPT, and this prevent the appearance of renal osteodystrophy (ROD) in dialysis patients.


[A case of anti-GBM nephritis (crescentic glomerulonephritis) associated with membranous nephropathy].

We report a case of endstage renal disease due to simultaneous occurrence of membranous nephropathy and crescentic glomerulonephritis associated with anti-GBM antibodies. The patient was a 60-year-old male and was hospitalized for prolonged anorexia and general malaise. On admission, his body temperature was 38.5 degrees C. Urinalysis revealed 3+ proteinuria and the sediment contained abundant erythrocytes. The urea nitrogen was 142.4 mg/dl, the creatinine 19.5 mg/dl, the potassium 6.47 mEq/dl and CRP 10.1 mg/dl. Anti-GBM antibodies were 1000EU/ml. Immediately after initiating hemodialysis, pulse steroid therapy, plasma exchange and continuous heparinization were performed. However, renal function had been impaired and maintenance hemodialysis was required. Histological examination of the renal specimen revealed marked epithelial crescent formation, whereas thickening of basement membrane and mesangial proliferation were not observed. By immunofluorescent staining, both bright linear and fine granular fixation of IgG and fine granular fixations of C3 along the glomerular capillary walls were observed. Electron microscopy showed subepithelial electron lucent deposits and thickening of the glomerular basement membrane, diagnostic of the advanced membranous nephropathy (stage IV).


[A case of progressive systemic sclerosis complicated by crescentic glomerulonephritis and diffuse pulmonary hemorrhage].

A 38-year-old man was hospitalized for proteinuria, and pitting edema. He had noticed Raynaud's phenomenon at about age fifteen. One month prior to admission, his urine contained protein and the serum creatinine was 3.0 mg/dl. On admission, sclerodactylia, digital pitting scar of fingertips, digital bone absorption and pulmonary fibrosis were observed and a diagnosis of progressive systemic sclerosis (PSS) was made. Laboratory investigations revealed: 24-hour urine protein excretion 3 g; serum creatinine 5.6 mg/dl; creatinine clearance 13.5 ml/min; antinuclear factor strongly positive in a speckled pattern; antibodies to nRNP positive with a titer of 1: 20, 480; antibodies to DNA, Sm, SS-A, SS-B, Scl-70, centromere and Jo-1 negative; serum complement normal. A renal biopsy revealed focal and segmental necrotizing glomerulonephritis with 70% crescents but no vascular changes. Circulating antiglomerular basement membrane antibodies were negative. Immunofluorescence disclosed granular deposits of IgM and C3 in the mesangium and along the capillary walls. Treatment was begun with methylprednisolone pulse therapy. After 5 month, serum creatine and creatinine clearance were 1.9 mg/dl and 35 ml/min, respectively. A year after the discharge, he was readmitted for hemoptysis and worsening of proteinuria and microhematuria. A chest radiograph demonstrated bilateral alveolar consolidation. Serum creatinine was elevated to 3.5 mg/dl. The continuous hemoptysis resulted in a severe dyspnea associated with a rapid fall in the hemoglobin. On the fourth hospital day, the PaO2 was 41 Torr on oxygen by mask that necessitated mechanical ventilation and pulse therapy was started. However, the patient died on the ninth hospital day of respiratory failure due to pulmonary hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)


[A case report of lupus nephritis associated with minimal change nephrotic syndrome--comparison of various histological types of 67 cases with lupus nephritis].

A 22 year old male of lupus nephritis associated with minimal change nephrotic syndrome was described. The patient was well until 4 years earlier, when Raynaud's phenomenon and photosensitivity developed. One week before admission, edema appeared suddenly and proteinuria was pointed out on July 28, 1990. On admission, his legs, ankles, and eyelids were edematous. There was no sclerodactylia, although Raynaud's phenomenon was positive when his hand disclosed to the cold. Urinalysis showed heavy albuminuria (10.4g/day), but urinary sediment showed no abnormality. Immunological examination showed positive antinuclear antibody, determination at a titer of 1: 160 with a speckled pattern. Anti-RNP and anti-Sm antibody were positive. However, neither anti-DNA antibody nor hypocomplementemia was detected. There was high concentration of serum IgE (2564IU/ml). Renal biopsy was performed. Light microscopic study showed slight increase of mesangial cells and matrix. Immunofluorescence study showed mesangial localization of IgG and C3. Electron microscopic study showed electron dense deposits only in the mesangial area. The diagnosis of lupus nephritis associated with minimal change nephrotic syndrome (MCNS) was made and administration of PSL was started. Proteinuria disappeared after 3 weeks and nephrotic syndrome remitted completely. The case of lupus nephritis associated with MCNS is very rare. Therefore, the relationship between amounts of proteinuria and various histological types of 67 cases with lupus nephritis which we experienced at our hospital was evaluated. Results showed that nephrotic range proteinuria was not present in mesangial lupus nephritis. So, it was concluded that if heavy albuminuria was found in mesangial lupus nephritis, we should consider the possibility of lupus nephritis associated with MCNS.


[A case of acute renal failure in a patient with idiopathic hypouricemia].

This report is a 17-year-old man with an acute renal failure who complained of nausea, vomiting, bilateral loin pain and abdominal pain after scuffle. Renal biopsy specimen obtained from the left kidney revealed acute tubular necrosis. After recovering renal function he showed extreme hypouricemia (serum uric acid, 0.6 mg/dl) and elevated uric acid clearance (62-78 ml/min). The fractional excretion of uric acid (CUA/Ccr) could not be influenced by either oral pyrazinamide or probenecid. As no other renal tubular or metabolic abnormalities were detected, it is suggested that presecretory reabsorption defect or subtotal defect in uric acid transportation was responsible for the hypouricemia in this patient.


[A case of acute renal failure due to left contracted kidney, complicated by right renal infarction].

A 46-year-old woman, who had been treated with anti-arrhythmic drugs and digitalis for mitral stenosis and paroxysmal atrial fibrillation, suddenly developed severe abdominal pain and nausea. There was tenderness around right CVA. BUN and serum-creatinine were elevated, 57 mg/dl and 4.5 mg/dl respectively. She was in acute renal failure (ARF). WBC, GOT, GPT, LDH were also elevated. Abdominal ultrasonography showed normal-size right kidney (12 cm) and atrophic left kidney (8.5 cm). Selective right renal angiography revealed right renal arterial embolism, suggesting that ARF developed from right renal infarction complicated by left atrophic kidney. Renal scintigram using 99mTc-DTPA indicated non-function type left kidney. Because of the high risk of surgery, she received anticoagulant therapy. Fifteen days later, BUN and serum-creatinine returned to 14mg/dl, 2.2mg/dl, respectively.


[Double filtration plasma pheresis was effective on the recurrence of pulmonary hemorrhage after renal transplantation: report of a case].

A 35-year old female with an autoimmune disease complaining of recurrent hemoptysis and macrohematuria had received a renal transplantation from her mother. After transplantation, recurrence of pulmonary hemorrhage occurred twice. First recurrence followed the peritonitis with ileal perforation. Steroid pulse therapy had no effect on this recurrence, while double filtration plasmapheresis was effective. During this treatment, renal function was not failed. Second recurrence followed acute rejection that was cured with the OKT3-rescue therapy. DFPP therapy was effective on this episode. Pulmonary hemorrhage was caused by auto immune reaction and acute rejection caused by transplant immune reaction were recognized independently, and they needed different treatment. According to this clinical course, we consider the relation between auto immune reaction and transplant immune reaction was as follows. T cell activation caused by primary transplant immune reaction may have no direct influence on auto immune reaction. Peritonitis and rejection may induce auto immune reaction. We suppose that this auto immune reaction was caused by humoral factor, because auto immune reaction was controlled by DFPP.


Studies on the outcome of lupus nephritis according to long-term treatment employing different modes of immunotherapy.

The outcome of long-term treatment of lupus nephritis under different immunotherapies, together with the factors affecting the outcome of lupus nephritis, was studied. A total of 212 lupus nephritis patients were classified into 5 groups according to their different modes of treatment: (1) initial dose of prednisolone (PSL) below 39 mg/day, (2) initial dose of PSL above 40 mg/day, (3) pulse therapy and steroids, (4) steroids and immunosuppressants, and (5) combination therapy of plasmapheresis with other therapies. The outcome of lupus nephritis was evaluated into 5 grades. As a result, the complete remission rate of lupus nephritis was 9.4%. The 5-year survival rates increased with all modes of treatment. However, it was impossible to identify which mode of therapy could bring about the highest rate of remission. Decreases in extrarenal involvement and low complement levels were observed together with increases in IgM anti-DNA antibodies among the lupus nephritis patients with remission.


Plasma dopamine, urinary dopamine and their metabolites in chronic renal failure.

To assess the clinical features of the dopamine (DA) metabolism in chronic renal failure patients (CRF), measurements were made of the plasma DA, norepinephrine (NE), epinephrine (EN) and their urinary metabolites in 6 healthy controls and 13 CRF patients before and after administration of oral DA (KW-3160, Kyowa Hakko Kogyo Co., Ltd.). The data obtained, including that for impaired DA metabolites in the patients with chronic renal failure, can be summarized as follows: I) Synthesis: In the plasma, the DA, NE and EN levels were not significantly different in the CRF patients as compared to those in normal controls, but the excretions of urinary free DA, NE and EN were markedly lower, and the free and conjugated DA, NE and EN levels were significantly decreased in the CRF patients after DA administration. These findings indicate that the plasma dopamine beta-hydroxylase activity is inhibited in CRF patients. II) Degradation: Increased levels of urinary free and conjugated 3,4-dihydroxy phenylacetic acid (DOPAC) and decreased levels of urinary conjugated homovanillic acid (HVA) were observed, indicating that the monoamine oxidase (MAO) activity in the plasma is possibly augmented, and the catecholamine O-methyl transferase (COMT) activity inhibited, in uremic patients. III) Excretion: The urinary excretions of free DOPAC, HVA, NE and vanillylmandelic acid (VMA) and of conjugated DA and DOPAC were significantly correlated with the creatinine clearance. These data suggest that the excretion of urinary DA and part of its metabolites may be regulated by the renal function.


Changes of enzyme activity levels in red blood cells in hemodialysis patients by recombinant human erythropoietin.

In a phase II clinical trial to test the ability of recombinant human erythropoietin (r-HuEPO) to reverse the anemia of patients undergoing hemodialysis, the changes of enzyme activity in red blood cells were evaluated in 5 hemodialysis anemic patients who were treated with r-HuEPO. Concerning the activity levels measured, the following conclusions are drawn. 1) HK, ALD, TPI, G6PD and 6PGD were statistically significantly increased at the time when the hematocrit has risen by 8% with the use of r-HuEPO. 2) The enzyme activity levels of PFK, GA3PD, MPGM, ENOL, PK, GR and ADA were higher than normal already before the r-HuEPO treatment. 3) The increases of HK and G6PD by r-HuEPO, as age dependent enzymes, may reflect the generation of young red blood cells. 4) In view of the fact that they are related to ATP production in the glycolysis cycle, we infer that increases of red blood cell enzymes by r-HuEPO may play at least some part in bringing a sensation of "well-being" to severely anemic patients undergoing hemodialysis.


Glomerular/tubular mixed-type proteinuria in a 3-year-old boy with mental retardation and hyperkinesis.

A 3-year-old boy with mixed glomerular/tubular proteinuria, mental retardation, and hyperkinesis is described. The proteinuria was discovered at the age of 3 years on urinary mass screening. Most of the urinary protein consisted of albumin, accompanied by increases in low molecular weight proteins, including beta 2-microglobulin and alpha 1-microglobulin. Mixed glomerular/tubular proteinuria is known to be caused by the following conditions: chronic renal failure, chronic pyelonephritis, cadmium poisoning, tubulointerstitial nephritis of various etiologies, and after strenuous, short-term, exhaustive exercise. The present patient did not display any of these disorders or conditions.


Familial juvenile nephronophthisis and renal transplantation in two siblings.

Familial juvenile nephronophthisis (FJN) is a hereditary renal disease, characterized by a juvenile onset and the development of medullary cysts and progressive renal damage. The pathogenesis of FJN remains unknown, and at present, no rational therapy other than renal transplantation is available. We describe two cases in siblings in whom there were no extrarenal complications, such as retinopathy or central nervous system involvement. Both patients display juvenile onset of the disease and end-stage renal failure. The brother received a kidney from his father, and the sister received a kidney from her mother. Recurrence of the underlying disease has not so far been found in the transplanted kidney.


Comparative effects of loop diuretics on AVP-receptor binding and AVP-sensitive adenylate cyclase activity.

The effects of loop diuretics (azosemide, ethacrynic acid and furosemide) on arginine vasopressin (AVP) receptor-adenylate cyclase components were compared in rat renal basolateral membranes. AVP binding was inhibited by these loop diuretics at concentrations above 10(-4) M. At the IC50 of azosemide and ethacrynic acid, the Kd values were significantly increased, while the Bmax values remained unchanged. These findings indicate an inhibitory effect of loop diuretics at high concentrations on the AVP binding to its receptors. Both the basal (AVP-unstimulated) and AVP-stimulated cyclic AMP productions were also inhibited by addition of these drugs. The inhibitions of the AVP binding and AVP-sensitive adenylate cyclase activity were dose-dependent. The above findings suggest that loop diuretics, especially azosemide and ethacrynic acid, can inhibit the basal and AVP-sensitive adenylate cyclase activities directly and also indirectly via the AVP receptor, at least in part. Comparing the loop diuretics, azosemide exerts a similar effect to ethacrynic acid, and they have a more potent antagonistic effect than furosemide with respect to AVP adenylate cyclase activation.


Effects of creatinine, creatol and methylguanidine on renal function.

Creatinine (Cr), creatol or methylguanidine (MG) was administered intraperitoneally to normal rats, and several renal function parameters were examined in an attempt to clarify the pathology under the various conditions. The glomerular filtration rate, renal plasma flow and renal blood flow after administration of Cr remained virtually unchanged when compared to those in the control group. In contrast, administration of creatol induced a significant decrease in these renal functions. Further decreases in the renal functions were observed in the rats given MG. However, the level of serum MG was extraordinarily high in the rats given creatol or MG. The toxic effects are discussed on the basis of the above results.


Study on the inhibitory effect of uremic plasma on lipoprotein lipase.

An investigation was undertaken to determine which plasma factors from normal controls and patients with chronic renal failure (CRF) exert have inhibitory effects on the activity of lipoprotein lipase (LPL) purified from heparinized human plasma by using an accurate LPL assay system. Inhibitors of LPL were found to be present in the plasma. The inhibition of the LPL activity was significantly greater in CRF patients than in normal controls. Following hemodialysis (HD), the same concentration of uremic plasma led to less inhibition. The inhibitors existed only in lipoprotein deficient plasma (LPDS), which demonstrated an LPL-inhibitory activity at extremely high concentrations with a significant difference between the patients and normal controls. There was no difference between the two groups at low concentrations. A specific inhibitory effect on LPL in LPDS was noted in the 7S and 4S fractions separated by gel filtration employing Sephacryl S-200 column chromatography. The inhibitory effect of the 7S fraction was found to be dependent on the concentration, and the difference between the two groups was similar to that for LPDS. The results obtained in the present study suggest that the plasma from CRF patients exhibited a strong inhibitory action on the LPL activity as compared to the plasma from normal controls, and the inhibitory action was due primarily due to poor excretion of dialyzable inhibitors.


Effect of hyperlipidemic serum on cultured mesangial cells.

Hyperlipidemia may contribute to the progression of focal glomerular sclerosis (FGS) in humans and obese Zucker rats. Zucker rats undergo an increase in their plasma low density lipoprotein (LDL), very low density lipoprotein (VLDL) and oxidized lipids, resulting in the development of FGS. We examined the effects of such hyperlipidemic serum on thymidine uptake into cultured mesangial cells. LDL and VLDL both stimulated the overnight uptake of 3H-thymidine at a concentration of below 10 micrograms/ml and inhibited this uptake at over 50 micrograms/ml in the medium. Modified LDL and VLDL after oxidation, however, inhibited this uptake at a concentration of 1 microgram/ml in the medium. Although 20% serum-containing medium stimulated the thymidine uptake by the mesangial cells, the lipoprotein fraction inhibited the uptake, while the lipoprotein-free fraction markedly stimulated it. We conclude therefore that the lipoproteins in hyperlipidemic serum suppress and the lipoprotein-free fraction stimulates mesangial growth. Both may play a role in the development of FGS in rats.


Urine concentration adjustment with a dipstick is dispensable for urinary beta 2-microglobulin screening in children.

Single voided urine was collected from 1,699 3-year-olds. The urinary beta 2-microglobulin levels (microgram/l) were measured by ELISA. The frequency of the levels was distributed with a wide base on the right side, even after logarithmic transformation. The upper limits of the 98% confidence interval were 660 micrograms/l for boys and 690 micrograms/l for girls. The values adjusted to a specific gravity of 1,020 in a total of 1,468 urine samples, of which the specific gravity was examined with Nephrosticks L, from 746 boys and 722 girls were similarly distributed, and the upper limits of the 98% confidence interval were 550 micrograms/l for boys and 530 micrograms/l for girls. There was no significant sex-related difference. Of the 14 children who had adjusted beta 2-microglobulin values above the adjusted upper limit of the 98% confidence interval, 11 (79%) had actual levels above the actual upper limit of the 98% confidence interval, 11 (79%) had actual levels above the actual upper limit of the 98% confidence interval. Finally, 2 children (one boy and one girl) proved to have renal disease. In these 2, both the actual and adjusted values exceeded the respective upper limits of the 99% confidence interval. Concentration adjustment appears to be dispensable in the screening for renal disease. In practice, 600 micrograms/l would serve as an actual cut-off level for both sexes with safety.


Increased remission of early stage membranous nephropathy on long-term treatment with corticosteroid.

Sixty-five patients with primary membranous nephropathy were examined in order to assess the effects of long-term treatment with corticosteroid. The observation period varied from 8 to 279 months (average, 95 months). The patients were treated with corticosteroid alone or with combinations of corticosteroid and immunosuppressants, nonsteroidal anti-inflammatory drugs (NSAID) and/or dipyridamole. At 6 months after treatment, only 14% of the patients had achieved complete remission. At 24 months after treatment, 46% of the patients showed complete remission. The rate of clinical remission, i.e. complete and incomplete remission, was markedly increased in stage I and II patients with membranous nephropathy by Ehrenreich and Churg's classification but not in stage III patients. The actuarial survival curve indicated that 84% of the patients were alive at 10 years after onset. These data suggest that active treatment with corticosteroid is beneficial for patients with primary membranous nephropathy.


A stable metabolite, Arg-Pro-Pro-Gly-Phe, of bradykinin in the degradation pathway in human plasma.

Degradation of bradykinin (BK) in human plasma was investigated by searching for a stable metabolite as a marker of kinin release in vivo. BK, incubated with diluted plasma, was degraded to des-Arg9-BK (des-9-BK), des-Phe8-Arg9-BK (des-8,9-BK) and Arg-Pro-Pro-Gly-Phe ([1-5]BK). Des-9-BK was degraded to [1-5]BK without an increase in des-8,9-BK, and des-8,9-BK was also degraded to [1-5]BK. D,L-2-Mercaptomethyl-3-guanidinoethyl-thiopropanoic acid inhibited the formation of des-9-BK from BK, whereas captopril inhibited the formation of des-8,9-BK from BK as well as that of [1-5]BK from des-9-BK or des-8,9-BK. The half lives of BK, des-9-BK, des-8,9-BK and [1-5]BK under the present experimental conditions were 60 min, 90 min, 14 min and 4.2 hr, respectively. Among the metabolites, [1-5]BK was the most stable one and may be used as a marker for BK production in vivo.


Amphetamine-antagonistic property of 4-phenyltetrahydroisoquinoline: effect on noradrenaline release in spinal cord slices.

The amphetamine-related compounds methamphetamine, phenylethylamine and nomifensine increased the K(+)-evoked release of endogenous noradrenaline from rat spinal cord slices. 4-Phenyl-1,2,3,4-tetrahydroisoquinoline (4PTIQ), which alone did not affect the K(+)-evoked release of noradrenaline, inhibited the noradrenaline-releasing effects of methamphetamine, phenylethylamine and nomifensine. 4PTIQ revealed a weak noradrenaline-uptake inhibitory effect, and the effect was weaker than those of desipramine and nomifensine. These results showed that 4PTIQ is an antagonist against the amine-releasing effects of amphetamines.


The flexor reflex mediated by group II afferent fibers: effects of morphine-HCl and mephenesin.

The effects of morphine-HCl and mephenesin on the flexor reflex mediated by group II afferent fibers were investigated. The flexor reflex was recorded by means of the electromyogram (EMG) evoked in the muscle tibialis anterior by stimulation of the ipsilateral tibial nerve in urethane-alpha-chloralose anesthetized rats. Afferent volleys corresponding to the phasic EMG component of the flexor reflex with 7.6-msec latency (flexor EMG: fEMG) were also recorded using the double volley technique. The threshold of the afferent volleys mediating the fEMG was approximately twice as high as that of the most excitable afferent volleys, which were considered the spikes of group I afferent fibers, and the conduction velocity of the afferent volleys was 39.9 +/- 3.2 m/sec. Morphine-HCl (5 mg/kg, i.v.) did not change the amplitude of the fEMG, but mephenesin (40 and 80 mg/kg, i.v.) depressed it dose-dependently. These results suggest that the fEMG is a flexor reflex mediated by group II afferent fibers, which is not affected by morphine-HCl but depressed by mephenesin.


The effects of the serotonin1A receptor agonist buspirone on the blood glucose and pancreatic hormones in rats.

The effects of the serotonin1A (5-HT1A) receptor agonist buspirone on the plasma glucose and pancreatic hormones insulin and glucagon were investigated in rats. Buspirone elicited significant hyperglycemia and hyperglucagonemia, although it did not affect the insulin levels. Adrenodemedullation inhibited both the increase in blood glucose and glucagon levels. These results indicate that buspirone-induced hyperglycemia and hyperglucagonemia are mediated by adrenaline release from the adrenal gland.


In vitro oxygenation injury to slices prepared from ischemic kidney in rats.

When cortical slices prepared from rat kidneys made ischemic were incubated under a 100% oxygen atmosphere, lipid peroxidation increased and the ATP level decreased. Such oxygenation of the slices was accompanied by decreases in gluconeogenesis and the glutathione level, but an antioxidant, N,N'-diphenyl-p-phenylenediamine, prevented the increase in lipid peroxidation without affecting decreases in ATP and glutathione levels, and gluconeogenesis. The results suggest that postischemic oxygenation of slices generates free radicals that cause the production of lipid peroxidation not associated with tissue injury.


Studies on the mode of action of ambrein as a new antinociceptive compound.

The compound ambrein was isolated from ambergris, which is commonly used as an analgesic in the Saudi folklore medicine. The LD50 of ambrein, given intraperitoneally (i.p.) in mice, was found to be high (7.5 g/kg), and ambrein proved to be a safe compound in this species. In the hotplate test, ambrein was found to possess antinociceptive activity in mice at doses which did not sedate or incapacitate the animals. By the i.p. administration route, ambrein produced antinociception in mice at a dose as low as 10 mg/kg. The antinociceptive activity of ambrein (250 mg/kg i.p.) was inhibited by a noradrenergic neurotoxin (DSP-4) and by naloxone, methysergide or prazosin. It was not influenced by a serotonin depletor, p-chlorophenylalanine. The possible mechanism of ambrein antinociception is discussed.


Inhibitory effect of a novel antianginal agent, E4080, on ST segment elevation induced by vasopressin in anesthetized guinea pigs.

We compared the antianginal effect of E4080, a novel bradycardiac agent with coronary vasodilating properties, with those of a bradycardiac agent and some coronary vasodilators in vasopressin-induced anginal model of guinea pigs. An i.v.-administration of vasopressin (0.2 IU/kg) produced an ST segment elevation on electrocardiograms (ECG) of 0.30 +/- 0.05 mV from the baseline within 30 sec in anesthetized guinea pigs. The ST segment elevation on ECG was used as an index of myocardial ischemia. E4080 and other drugs were injected i.v. 5 min before the administration of vasopressin. E4080 at 5 mg/kg depressed the ST segment elevation induced by vasopressin to 0.06 +/- 0.01 mV (20% of control, n = 6, P < 0.001). However, alinidine (5 mg/kg), which produced the same bradycardic action (reduction of heart rate by 50%) as that of E4080, tended to inhibit the ST segment elevation, but this was not statistically significant. On the other hand, other vasodilators such as isosorbide dinitrate (0.3 mg/kg), nifedipine (0.1 mg/kg) and lemakalim (1 mg/kg) also significantly reduced the ST segment elevation to 0.16 +/- 0.03, 0.08 +/- 0.04 and 0.09 +/- 0.03 mV, respectively. These results suggest that the inhibitory effect of E4080 on the ST segment elevation induced by vasopressin is due to the coronary vasodilating effect rather than the bradycardiac effect, and that E4080 would be useful as an antianginal agent.


Inhibitory effects of hyaluronan on [14C]arachidonic acid release from labeled human synovial fibroblasts.

The effects of hyaluronan (HA) on the release of arachidonic acid (AA) from phospholipids induced by bradykinin in synovial fibroblasts of osteoarthritic patients were examined. HA inhibited [14C]AA release from prelabeled synovial cells stimulated with and without bradykinin 1 hr after incubation with HA and thereafter. The inhibitory effects of HA on [14C]AA release were dependent on the concentration and molecular weight of HA. However, inhibition of [14C]AA release by HA was not merely due to the viscosity of HA. The [14C]AA release induced by calcium-ionophore A23187 was also inhibited by HA with a high molecular weight. In addition, HA did not affect [14C]AA uptake by the cells. Our results suggest that HA with a high molecular weight elicits anti-inflammatory effects, at least in part, by inhibiting AA release in inflamed joints.


Existence of a human urinary trypsin inhibitor (urinastatin)-like substance in the rat brain.

A human urinary trypsin inhibitor, urinastatin (UT)-like immunoreactive substance with trypsin inhibitory activity, was demonstrated in certain brain regions in rats, especially the cerebral cortex, hippocampus and hypothalamus. Although this UT-like substance in the rat brain displayed an N-terminal amino acid sequence similar to that of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), it did not show any GAPDH activity. These results indicate that the UT-like substance in the rat brain is a protein different from GAPDH and indicates a localized distribution within certain brain regions partly related to learning and memory.


[Anatomy and function of the upper urinary tract].

This report deals with the histologic and gross anatomy of the upper urinary tract (calyces, pelvis, and ureter) as well as the nerve supply to this region. It also covers the physiological transport of urine from the kidneys to the bladder, which is reviewed on the basis of experimental and clinical studies. A pacemaker system present in the proximal calyces has been found to have an important physiological role in urine transport. However, clinical experience has shown that urine transport is not affected by surgery such as pyeloplasty and pyelolithotomy which impairs the activity of this pacemaker. Electron microscopic and histochemical studies as well as the maintenance of urine transport after renal grafting suggest that the nerve supply to the upper urinary tract is not dominant in regard to this function. This study also investigated urinary transportation in the presence of urinary tract obstruction due to various diseases, and demonstrated that urine is also conveyed by gravity and not solely by ureteric peristalsis. The use of internal stenting and percutaneous urinary diversion thus appears to be reasonable. Although the detailed etiology congenital hydronephrosis is still unknown, there is no doubt that it involves dysfunction of the ureteropelvic junction, since urine transport is improved by the endoscopic or surgical formation of a physiological tunnel at this junction which can regulate the volume of urine transported according to urine output. It is important for studies of upper urinary tract function to be conducted in close relation to clinical practice and not to simply be confined to esoteric experimental situations.


[Immunohistochemical classification and ultrastructural study of hyperparathyroidism].

Immunohistochemical and ultrastructural studies were performed on cases with hyperparathyroidism. The relationship between histology and cell activity in hyperfunctioning parathyroid glands was studied. Furthermore, the synthesis-secretion process of parathyroid hormone (PTH), which has been more or less elucidated biochemically, was studies by a morphological means. The subjects employed in the present study were 23 cases of primary hyperparathyroidism (PHPT) and 31 cases of secondary hyperparathyroidism (SHPT). Based on the results of the immunohistochemical study using anti-PTH antibody, the histology of the parathyroid gland was classified into 4 types: type A; sporadic cells showing intense yellowish brown staining in their cytoplasm, type B; glandular cells showing intense yellowish brown staining specifically in their cytoplasm, type C; as a whole the cells were weakly stained, but intensely stained cells were absent, and type D; only the cytoplasm of large cells showed uniform and intense yellowish brown staining. In both PHPT and SHPT, type C constituted about 80%. On the other hand, all water clear cell hyperplasia in SHPT showed type D staining. Electron microscopic studies performed on the hyperparathyroidism revealed that the rough endoplasmic reticulum and Golgi apparatus, which are related to the synthesis of PTH, were well developed. Immunoelectron microscopy revealed that only the secretory granules were specifically stained with the anti-PTH antibody. This finding suggests that PTH becomes active once it reaches the secretory granule.


[The relationship between morphology and cell activity in hyperparathyroidism].

The relationship between tissue morphology and cellular activity in hyperparathyroidism was investigated by 2-color flowcytometry and an immunohistochemical technique using anti-parathyroid hormone (PTH) antibody. A total of 21 cases were employed, which included 8 cases of primary hyperparathyroidism (PHPT) and 13 cases of secondary hyperparathyroidism (SHPT). The results of 2-color flowcytometry on DNA ploidy pattern revealed that all the 8 PHPT cases were diploids. In SHPT, however, there were 9 diploids (69.2%), 2 tetraploids (15.4%) and 2 aneuploids (15.4%). Electron microscopic studies were performed on the diploid 2c and 4c peak cells, which were obtained by individually sorting the cells from each cycle. As a result, these cells were found to possess well developed rough endoplasmic reticulum and Golgi apparatus. These cells in general showed weak immunostaining. Furthermore, numerous secretory granules were found in the cells obtained from abnormal peak of aneuploid when compared to diploid cells. In tetraploids and aneuploids, the darkly stained cells and glandular cells showed intense immunostaining. These cells contained numerous secretory granules and they were thought to possess high cellular activity.


[Lysis of autologous tumor cells by peripheral blood lymphocytes treated with IFN-alpha in patients with renal cell carcinoma].

Immunotherapy, consisting mainly of interferon (IFN) therapy, has been used to treat renal cell carcinoma refractory to radiotherapy and chemotherapy ever since IFN was reported to be effective against renal cell carcinoma in 1982. The efficacy of IFN is low, with the response rate being only about 20% and the method and duration of its administration have yet to be established. Using viable tumor cells obtained at nephrectomy, we discovered that IFN-alpha induced killer cells have a cytocidal effect on autologous renal cell carcinoma cells and that assaying the cellular immunity of the peripheral blood lymphocytes of 25 patients with renal cell carcinoma, using ACHN derived from human renal cell carcinoma as the target cells, is useful as a monitoring method during IFN-alpha therapy. Augmentation of the cytotoxicity of peripheral blood lymphocytes in response to administration of IFN-alpha was observed in all 25 cases. Cytotoxicity was activated to 5-426 LU compared with the control value of 1 LU or less before IFN therapy, when autologous renal cell carcinoma cells were used as the target cells. Cytotoxicity for ACHN cells in the control value before IFN-alpha therapy and 4 weeks after the institution of IFN-alpha administration and autologous tumor lysis in the induction assay were more strongly correlated than in the case of K562 cells. A strong correlation was also found between cytotoxicity for ACHN cells in the induction assay and 4 weeks after the institution of IFN-alpha administration.(ABSTRACT TRUNCATED AT 250 WORDS)


[Surveillance after orchiectomy for stage I testicular seminoma].

The results of treatment by orchiectomy and radiotherapy for stage I testicular seminoma are excellent with cure rates exceeding 95% and relapse rates less than 5%. However, after the development of successful surveillance programs for stage I nonseminomatous testicular cancers, the role of radiotherapy has been questioned by some authors and they proposed a "surveillance policy" for these patients. The purpose of this study was to determine the percentage of patients cured by orchiectomy alone, percentage who ultimately required therapy for occult metastases, site of recurrence, and over-all cure rate and treatment morbidity. And these data were compared with those of adjuvant radiotherapy group retrospectively. Twenty seven patients were treated with adjuvant radiotherapy (RT group). Since 1986, 23 patients with stage I testicular seminoma entered the "surveillance only" protocol at our institution (S group) with a follow-up between 14 and 70 months (median 43 months). Informed consent for the policy of surveillance was obtained. Follow up consisted of physical examination, determination of serum tumor markers and chest X-ray bimonthly for 2 years, every 3 months for 1 year, every 6 months for 2 years and annually thereafter to 10 years. CT scans were performed every 4 months for 3 years, every 6 months for 2 years. Two patients in S group (8.7%) relapsed at 4 and 7 months after orchiectomy with nonbulky retroperitoneal disease (less than 5 cm in diameter), whereas only 1 (3.7%) irradiated patients did so after 4 months.


[Clinical results of prophylactic intravesical chemotherapy on superficial bladder cancer using the dye exclusion assay].

A chemosensitivity test was carried out on superficial bladder cancer using the dye exclusion assay for the purpose of screening chemosensitive drugs for prophylactic intravesical chemotherapy. Bladder cancer cells of each patients were incubated, in vitro, in the presence of adriamycin, (2"R)-4'-0-tetrahydropyranyladriamycin, mitomycin C, pepleomycin and 4'-epi-adriamycin (500 micrograms/ml) at 5%, CO2, 37 degrees C for 2 hours. The cytotoxic effect of the drugs was evaluated by the ratio of stained cells by trypan-blue. The most effective drug was instilled postoperatively into the bladder 3 times for the first week, and every 2 weeks during the following 14 weeks. In 18 patients followed more than 4 months the prophylactic effect was evaluated. Fifteen of the 18 patients completed the protocol, but the remaining 3 patients failed to complete to the instillation because of severe irritability of the bladder. Tumor recurrence was demonstrated in two patients. Non-recurrence rates of tumors at 12 and 24 months were 93.8% and 82.0%, respectively. These results suggested that this rapid and handy assay was useful for the purpose of screening chemosensitive drugs for the intravesical chemotherapy.


[A hundred cases of multiple primary neoplasms in association with genitourinary cancer].

There were 970 patients who were diagnosed as having genitourinary cancer at Yamagata Prefectural Central Hospital between 1975 and 1990, and of whom 100 cases (10.3%) had multiple primary malignant neoplasms in addition to their genitourinary cancer. They were compared with 220 patients having single genitourinary cancer and 274 having benign prostatic hypertrophy without past histories of cancer. The genitourinary organs involved with cancers included the prostate (50 patients), urinary bladder (43 patients), ureter or renal pelvis (15 patients) and kidney (7 patients). In the prostate cancer, the incidental carcinomas occupied 30%. The other organs accompanying the genitourinary cancers included the stomach, lung and colon. In patients of multiple primary cancers, single genitourinary cancer and benign prostatic hypertrophy, positive family histories for cancer were observed in 40.0%, 37.7% and 33.2%, respectively, with no significant difference between these groups. Histories of smoking were observed in 54.0%, 38.2% and 34.3% respectively, with significant difference between the multiple primary neoplasm patients and the other 2 groups (p < 0.01). There were two cases in whom the second cancer could be possibly caused by the exposure to radiation for the first cancer. No oncotherapeutic drugs or occupational exposure could be seriously suspected of the cause of the second cancers in the present cases.


[Bladder tumors detected by transabdominal ultrasonography in the multiphasic health testing and services].

From August, 1989 to July, 1991, we carried out transabdominal ultrasonography for screening of abdominal and pelvic disease in regular health check-up at Mito Saiseikai Hospital. Of 5,706 screened examinees were ultrasonographically suspected of bladder tumor and subsequently received a cystoscopic examination. Cystoscopy confirmed bladder tumors in 9 of the 11 patients. Eight of the 9 cases showed no urological symptoms, while the remaining 1 case showed microscopic hematuria objectively. All of the 9 cases revealed a transitional cell carcinoma of low grade and low stage. The smallest tumor detected by ultrasonography was 5 mm in diameter. Transabdominal ultrasonography proved useful for diagnosis of the bladder tumor at its early stage in the mass screening. Therefore, it is recommended to perform lower abdominal ultrasonography as a routine examination of the multiphasic health testing and services.


[Morphological and physiological change in the dis-used bladder of hemodialysis patients].

We studied 48 patients who underwent renal transplantation during the period of July, 1983 and May, 1988 and were free of episodes of neurogenic bladder in the past history. The average age was 27.6 +/- 9.5 years old, and mean 24 hour urine output was 249 +/- 396 ml. Cystometry was performed preoperatively in 39 patients. The average bladder capacity decreased to 112 +/- 69 ml (n = 39) and only 29.0% of the patients exhibited normal compliance (> 50 ml/cmH2O) (n = 35). Biopsy of the bladder wall was performed in 22 patients during the operation. The purpose of this study is to ascertain what physiological and pathological change may occur in the disused human bladder with low capacity and low compliance. Response of muscle tissue to carbachol were examined in 7 specimens and that of isoproterenol were examined in 9 patients. The minimum concentration of carbachol at which muscle contraction was exhibited did not differ from that of the control group. The minimum concentration of isoproterenol at which autonomous muscle activity was completely inhibited increased in cases with decreased 24 hour urine output. ED50 value of inhibition by isoproterenol to the muscle contraction during field stimulation exhibited that the inhibitory action of isoproterenol on muscle contraction declined in the cases with decreased 24 hour urine output. Pathological change of the smooth muscle layer were observed in 17 patients. Muscle cell atrophy was recognized in 29.4% of the patients and vacuolar change of smooth muscle cells was seen in 64.7%. Muscle bundle atrophy was observed in 23.5% and fibrosis was seen in 52.9%.


[Usefulness of renal CT scan for analysis of nutcracker phenomenon].

Among 24 patients with confirmed left renal bleeding, 11 were diagnosed of having nutcracker phenomenon (NP) on the basis of the results of renal venography and pull-back pressure from the left renal vein to the inferior vena cava. Renal CT scan was performed for these 11 patients, and its usefulness as a means of diagnostic analysis was studied. The following results were obtained. 1. The left kidney was scanned at 5-mm intervals. The mean distance between the anterior surface of the abdominal aorta (Ao) and the posterior surface of the superior mesenteric artery (SMA) was 4.5 +/- 0.6 mm in the NP group, while it was 13.9 +/- 6.4 mm in the control group (p < 0.01). 2. Regarding the morphology of the left renal vein (LRV), tapering dilatation, i.e., funnel-like dilatation, from the left side of Ao was seen in the NP group. In the control group, the left renal vein showed a club-like shape continuing to the inferior vena cava and showed no dilatation. 3. Vascular structures indicative of collateral vessels were observed around the LRV in the NP group. If renal CT scan is performed at 5-mm intervals, the following CT finding are thought to be indicative of the nutcracker phenomenon; (1) a distance of 5 mm or less between Ao and SMA and (2) tapered dilatation of the LRV. This study suggests that renal CT scan is useful for diagnostic analysis of the nutcracker phenomenon.


[Usefulness of MR angiography in renal tumor].

MR angiography using a gradient-echo, pulse sequence FLASH (fast, low-angle shot) method during breath-hold with a "MAGNETOM H-15" scanner (1.5 Tesla; Siemens Medical System) was performed on 27 patients with renal tumor at our clinic between February 20, 1990 and September 30, 1991 and we studied to evaluate its usefulness. Of these 27 patients, 22 patients including one patient under hemodialysis treatment had renal cell carcinoma and one patient had oncocytoma pathologically proven from the excised specimens. The remaining four patients including two patients associated with inferior vena caval tumor thrombus were clinically diagnosed as renal cell carcinoma based on the result of imaging examinations such as excretory urography, ultrasonography, computed tomography and conventional angiography. However, they could not be operated on because their tumors were too advanced. By reconstruction of the data of consecutive coronal scans of the abdomen with Maximum Intensity Projection (MIP), the MR angiography could in all cases delineate abdominal blood vessels such as the abdominal aorta, inferior vena cava and renal arteries and veins simultaneously without any intravenous contract materials. Our present study revealed that MR angiography has some advantages, especially with regard to preoperative angiographic information about the abdomen of patients with renal tumor. That is, MR angiography can delineate many kinds of arteries and veins of the abdomen simultaneously and in a broader range, as well as it can be performed on the patients with hypersensitivity to iodinated contrast materials or renal insufficiency in a usual fashion.(ABSTRACT TRUNCATED AT 250 WORDS)


[The progression of renal damage in reflux nephropathy--clinical analysis of proteinuria in children with vesicoureteral reflux].

To clarify the mechanism for reflux nephropathy to progress to irreversible or marginal renal damages, this study was conducted. We studied 57 cases of VUR in children followed-up more than 3 years after anti-reflux operation and investigated the correlation between changes of urinary protein excretion and clinical data. In general, proteinuria is the most important feature heralding a poor outcome in patients with reflux nephropathy. 9 cases (15.8%) in our series were positive of proteinuria postoperatively. In this positive group, scarring grade had been higher and renal size had been smaller significantly before operation than in other group. From these facts, it would appear that prognosis of refluxing kidney was determined by volume of remnant kidney, and glomerular hyperfiltration of remnant nephron would affect the progression of reflux nephropathy. According to the relationship between changes of urinary protein excretion and scarring grade or renal size, poor prognosis (proteinuria will worsen) would be more than 5 of scarring grade score (cumulation of bilateral scarring grades, Smellie's a = 1, b = 2, c = 3, d = 4) and less than -4S.D. in cumulative renal ratio preoperatively. Then border to progression in reflux nephropathy was between 2 and 4 of scarring grade score, and between -2S.D, and -4S.D. in cumulative renal ratio. In this marginal progression urinary protein excretion and GFR were found to be 100-300 mg/day and 60-75 ml/min, respectively.


[Establishment of a new human renal cancer cell line (TC-1) and its productivity of interleukin-6 (IL-6)].

We established a new cell line (TC-1) from primary site of a renal cell carcinoma (RCC) patient. Its doubling time in tissue culture was 20 hours at 45th passage and mycoplasma contamination test was negative. The karyotypic analysis demonstrated a human karyotype with a modal number of 70. A consistent chromosomal abnormality was noted such as No. 4 monosomy, No. 7 trisomy and a loss of Y chromosome. Electron microscopic examination showed a brush border, vacuoles and abundant glycogen granules in the cytoplasm, which was compatible with RCC cells. This cell line was transplantable to nude mice and the grown tumor closely resembled the original tumor, i.e. clear cell type and hypervascularity. High titer of interleukin-6 (IL-6) was detected in the supernatant of TC-1 cell culture (approximately 5 ng/ml) as well as in sera of nude mice bearing this tumor (260 pg/ml). Exogenous IL-6 did not enhance the TC-1 cell proliferation as determined by cell count. Flow cytometric analysis could not demonstrate the existence of IL-6 receptor on the cell surface. These results suggested the produced IL-6 did not act as an autocrine growth factor in the cell line. Additional IL-1 alpha to the culture medium induced 3-4 times higher concentration of IL-6 in the culture supernatant compared with that of non-stimulating cells, while exogenous TNF alpha did not stimulate IL-6 production.


[Analysis of early and late complications and their origins in Kock continent urinary reservoir following technical modification].

Kock and associates have made a major contribution to the ideal continent urinary diversion by developing a method for creating a continent internal reservoir for urine using the ileum. However, substantial problems have unfortunately resulted due to early and late postoperative complications. In an effort to further elucidate this problem, we herein summarize the incidence of early and late postoperative complications following a series of technical modifications made in patients who underwent Kock continent ileal reservoir construction from our ongoing experience to develop more suitable modifications of this procedure. From January 1985 through December 1991, 47 patients have undergone Kock pouch construction for continent urinary diversion. Our basic technique utilized in this study was slightly modified from that described by Skinner et al. Based on our earlier experience, several changes in the technique were made. One major change is that one row of surgical staples fixes the created nipple to the back wall of the reservoir for the efferent limb, and a further 3-cm longitudinal mucosal incision is made through the outer layer of the intussuscepted ileal nipple and the opposite wall of the reservoir which are sewn to the reservoir edge. A total of eleven patients (11/47) suffered one or more early surgical complications. A 31.8% (7/22) morbidity with an operative mortality rate of 4.3% (2/47) and a 16.0 (4/25) morbidity were observed in the early phase and late phase, respectively. Prolonged urinary leakage from the ileal reservoir and/or through a pin hole in the afferent limb made by surgical staples was observed in six patients (27.3%) in the early phase.(ABSTRACT TRUNCATED AT 250 WORDS)