Resolution of metastatic bone lesions following combination therapy with active vitamin D3 analogue and interferon-alpha in a patient with renal cell carcinoma.
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Bone Neoplasms↗
Biomedical subjects
T Fujioka
Publications and source records attributed to T Fujioka.
Angiotensin-converting enzyme inhibitor-induced anemia and treatment for erythrocytosis in renal transplant recipients.
Erythrocytosis is not rare in renal transplant recipients, and phlebotomy is still the main treatment. Recently, the occurrence of angiotensin-converting enzyme (ACE) inhibitor induced anemia in patients on chronic hemodialysis and in renal transplant recipients has been reported. We herein report 5 transplant recipients whose hematocrit levels decreased while taking ACE inhibitors, including 2 patients treated with ACE inhibitors for erythrocytosis. The individual mean hematocrit values ranged from 35.0% to 54.7% before treatment and from 27.6% to 42.0% after treatment. The hematocrit level in the 2 patients with erythrocytosis decreased from 54.7% to 39.8% and 47.5% to 27.6%, respectively. Anemia improved after discontinuation or dosage reduction of the drugs. The patients were given the same immunosuppressive drugs, and had good renal function. ACE inhibitor-induced conspicuous anemia was not observed in the transplant recipient who received a kidney from a twin sibling and had not been taking any immunosuppressive drugs, nor in the 8 other patients with diabetes mellitus or chronic glomerulonephritis who served as controls. We conclude that ACE inhibitor-induced anemia may frequently arise in an immunosuppressed state. Based on these events, the ACE inhibitor can be used as a potent drug for erythrocytosis in post-transplant recipients.
Adult↗
[Intrascrotal epidermal cyst: a case report].
A 37-year-old male visited our hospital complaining of right scrotal mass formation. An elastic hard, fist-size mass was found in the right scrotum. Under the diagnosis of an intrascrotal benign tumor, the mass was removed. The tumor had no relation to the testis or epididymis. The surgical specimen weighted 220 g and measured 13 x 8 x 8 cm in size. Histopathological diagnosis was epidermal cyst of the intrascrotum. Epidermal cyst of the intrascrotum is a rare disease and only 13 cases have been previously reported in Japan.
Adult↗
[Rupture of an external iliac artery aneurysm into the bladder: a case report and review of the literature].
A case of fatal hemorrhage caused by rupture of the external iliac artery aneurysm into the urinary bladder is presented. The patient, a 58-year-old Japanese female, had undergone total hysterectomy, and post-operative therapeutic radiation, for uterine cancer in 1974. A vesicocecal fistula was observed, and surgical intervention for closure was performed in May, 1992. On July, 13, 1992, she presented with pulsating hemorrhage from the urinary bladder. Angiography was consistent with rupture into the bladder of an iliac artery aneurysm. Surgical intervention for closure of the aneurysm was performed but the aneurysm could not be resected. She had relapse of the fistula which became infected with methicillin-resistant Staphylococcus aureus (MR-SA), and died 3 months postoperatively. To the best of our knowledge, there have been only 3 cases in which an iliac artery aneurysm ruptured directly into the urinary bladder. This case indicates that resection of the aneurysm for therapy is a vital requirement.
Adult↗
[Relationship between molecular typing of Helicobacter pylori by PCR-RFLP analysis and specificity of disease].
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Bacterial Typing Techniques↗
The effect of enalapril and sairei-to on survival-time for the rat with subtotal nephrectomy.
The effect of an angiotensin-converting enzyme inhibitor, enalapril, and a Japanese medicinal plant named sairei-to, after administration either alone or in combination, on survival-time due to the protection of proteinuria and the preserving of renal function, was studied in the rat with subtotal nephrectomy. Resection of 2/3 of the left kidney and removal of the right kidney was performed in 28 male Wister rats (220-250 g). The rats were divided into four groups: (1) control (without sairei-to or enalapril); (2) with sairei-to (2.5% in rat chow); (3) with enalapril (50 mg/l in drinking water); and (4) the combination of enalapril and sairei-to. The actual survival-times until natural death after renal ablation in these four groups were 92 +/- 3, 128 +/- 8, 199 +/- 19, and 194 +/- 13 days, respectively. Urinary protein excretion and renal function were markedly protected in the enalapril-treated rats. Urinary endothelin excretion was also attenuated in enalapril-treated rats. Statistical analysis revealed the absence of benefits with sairei-to alone or in combination treatment. In conclusion, enalapril provides protection of proteinuria and preserves renal function, which results in a longer survival-time in the rats having subtotal nephrectomy. However, sairei-to does not show such beneficial effects.
Animals↗
[Serum pepsinogen response to therapy for Helicobacter pylori associated gastro-duodenal disease].
We investigated the effect of H. pylori therapy on serum concentrations of pepsinogens on 87 patients of gastro-duodenal disease. In addition, we intended to see whether serum pepsinogen can serve as markers of response to H. pylori eradication. In 48 successfully eradicated cases, there was a significant decrease in gastritis score, and was a significant fall in serum pepsinogen II (PG II) level, and was a significant increase in pepsinogen I/II ratio (PG I/II ratio). In contrast, no change in gastritis score, PG II, and PG I/II ratio were observed in 39 unsuccessfully eradicated patients. No change in serum pepsinogen I (PG I) level was observed in both groups. In provisional successfully eradicated cases in PG II of decrease greater than 30% in after treatment, there was a sensitivity of 83.3% and a specificity of 89.7%. For the PG I/II ratio of increased greater than 30% in after treatment, the sensitivity was 95.8%, and the specificity was 94.9%. These findings suggest that PG II, PG I/II ratio can be useful for clinical evaluation of eradication therapy.
Adolescent↗
Peptic ulcer recurrence after Helicobacter pylori eradication: a 5-year follow-up study.
OBJECTIVE: To investigate whether eradication of Helicobacter pylori prevents peptic ulcer recurrence in the long term. PATIENTS AND METHODS: We treated 81 patients with endoscopically proven H. pylori-related peptic ulcers (39 with gastric ulcers and 42 with duodenal ulcers) with either amoxycillin or clarithromycin in combination with a proton-pump inhibitor or a histamine H2-receptor antagonist. The patients were followed for a recurrence of peptic ulcers for at least 5 years. Recurrence was assessed by endoscopy and the status of H. pylori was evaluated by culture, a rapid urease test and a histological examination. RESULTS: After 5 years of follow-up, the rate of recurrence of H. pylori-related duodenal ulcers decreased significantly (P < 0.0001) in the H. pylori-eradicated patients compared with non-eradicated patients. However, in the gastric ulcer group, there was no significant reduction in the recurrence rate. CONCLUSIONS: Our findings suggest that eradication of H. pylori significantly reduces the rate of duodenal ulcer relapse and that this relapse is associated with the presence of H. pylori. Therefore, H. pylori eradication may be considered a definitive cure for duodenal ulcers.
Adolescent↗
Influence of Helicobacter pylori infection and the effects of its eradication on gastric emptying in non-ulcerative dyspepsia.
AIM: The aim of the present study was to clarify the effects of Helicobacter pylori infection and its eradication on gastric emptying. SUBJECTS AND METHODS: Out of a total of 52 patients with non-ulcerative dyspepsia, 34 H.pylori-positive patients were enrolled. Antimicrobial drugs for the eradication of H. pylori were administered to 19 out of the 34 H. pylori-positive patients. Gastric emptying was evaluated according to the acetaminophen method. Inflammatory changes and intracellular periodic acid-Schiff-positive substances in the antral mucosa were examined in biopsy specimens. RESULTS: Although gastric emptying was significantly prolonged in the patients with non-ulcerative dyspepsia compared with the control group (P < 0.01), there was no difference in gastric emptying between H. pylori-positive and -negative patients, with all patients showing significantly less gastric emptying than the control group. The H. pylori eradication rate was 58% (11 out of 19) and gastric emptying improved significantly in seven patients whose infection was eradicated and whose dyspeptic symptoms disappeared. The ammonia concentration in gastric juice, inflammatory changes in the gastric mucosa and the index of periodic acid-Schiff-positive substances improved significantly when H. pylori was successfully eradicated compared with patients in whom eradication was unsuccessful. As gut hormones may affect gastroduodenal motility associated with H. pylori infection, we also studied the levels of serum gastrin and cholecystokinin. In the patients whose infection was eradicated, serum gastrin decreased significantly, but the cholecystokinin level did not change significantly, although there was a non-significant trend for cholecystokinin to increase. CONCLUSIONS: These results suggest that delayed gastric emptying is partly associated with H. pylori infection and that the infection may contribute to the development of non-ulcerative dyspepsia.
Adult↗
[Retroperitoneal leiomyoma: a case report].
The patient was a 40-year-old woman who was hospitalized for edema of whole body. On admission, ultrasonography, CT scan and MRI revealed bilateral hydronephrosis due to retroperitoneal large tumors. The angiography showed hypervascular tumors in the pelvis. These tumors were surgically removed and the histology was leiomyoma. The retroperitoneal leiomyoma is rare and only 16 cases have been reported in the literature besides our patient.
Adult↗
Anti-AIDS agents. 15. Synthesis and anti-HIV activity of dihydroseselins and related analogs.
Forty-two dihydroseselins based on the structure of suksdorfin (1) were synthesized in order to evaluate their anti-HIV activity. These synthetic derivatives include 3',4'-di-O-acyl- and 3'- or 4'-O-acyl-cis-dihydroseselins (8-21) and 3',4'-trans-dihydroseselins with O-acyl and/or O-alkyl groups at the 3' and 4' positions (6, 22-43). Two 4'-azido (44, 45) and three 4'-alkylamido (46, 48, 49) derivatives were also prepared. By using optically pure reagents, three pairs of diastereoisomers were synthesized and separated as optically pure compounds (14, 15; 16, 17; 38, 39). Together with the above synthetic derivatives, seselin (3) and (+/-)-cis-(4), (+)-cis- (5), and (+/-)-trans-dihydroseselin-3',4'-diol (7) were also tested for their in vitro anti-HIV activity. An optically pure compound, 3',4'-di-O-(-)-camphanoyl-(+)-cis-khellactone (16), showed potent inhibitory activity and remarkable selectivity against HIV replication. The EC50 value and in vitro therapeutic index (TI) of 16 are 4 x 10(-4) microM and 136,719, respectively, which are better than those shown by AZT in the same assay. In addition, compound 16 is also active against HIV replication in a monocytic cell line and in peripheral blood mononuclear cells (PBMCs). Our in vitro assay indicated that, like compound 1, compound 16 is not an inhibitor of HIV-1 reverse transcriptase. Moreover, the anti-HIV activity of 16 is stereoselective as its three diastereoisomers (17, 38, 39) are at least 10,000 times less active. Since other synthetic dihydroseselin derivatives with different substituents or without any substituents are inactive or are active only at much higher concentration, the antiviral potency of 16 could be associated with the camphanoyl moieties of its structure. Therefore, compound 16 represents a unique coumarin structure with promising anti-HIV activity.
Acquired Immunodeficiency Syndrome↗
[Results of surgical treatment of aortic dissections].
From January 1989 to September 1993, 59 consecutive patients (35 males and 24 females, mean age 59.6 years old) underwent surgical repair of aortic dissection on the cardiovascular surgical unit at Takeda Hospital. The type of aortic dissection were classified according to Stanford University criteria. Twenty-two patients had acute type A (Ac-A), 10 had chronic type A (Ch-A), 4 had acute type B (Ac-B), and 23 had chronic type B (Ch-B) dissection. Seventeen dissections (29%) in the entire group of 59 cases had ruptured (including cardiac tamponade, pleural effusion and hemoptysis etc.). Ischemia of lower extremity occurred in 7 patients and ischemia of visceral organs in 3 patients. Type A dissection were approached via a median sternotomy and cardiopulmonary bypass with systemic hypothermia. Type B dissections were approached through a left postrolateral thoracotomy. Left heart bypass (left atrial-femoral in 8 cases) and partial cardiopulmonary bypass (femoral-femoral in 12 cases) generally were utilized. Resection of intimal tear and replacement of aorta with vascular grafts (including aortic arch in 19 cases) were performed in most patients and primary closure of the intimal tear was performed in 9 cases using GRF. The over-all operative mortality rate was 36% (8/22) for Ac-A, 20% (2/10) for Ch-A, 25% (1/4) for Ac-B, 22% (5/23) for Ch-B. Main causes of operative death was perioperative brain damage. It is necessary to improve the operative mortality for Ac-A dissections (especially in replacement of aortic arch and arch vessels). Further researches are needed regarding optimal methods of the cerebral protection during reconstruction of aortic arch.
Adult↗
Genetic alteration of the hepatitis C virus hypervariable region obtained from an asymptomatic carrier.
Hepatitis C virus (HCV) genome shows extensive sequence diversity at 2 hypervariable regions (HVR1 and HVR2) of the putative envelope glycoprotein (gp70). We recently reported that the amino-acid sequence of HVR1, but not of HVR2, underwent a striking mutation or mutated sequentially over a period of several months in patients with chronic hepatitis (CH). Here, we examined whether these genetic alterations in HVR1 occurred in an asymptomatic HCV carrier. The level of HCV RNA in serum was almost the same throughout the 4 time points sampled over 16 months. However, we found that the amino-acid sequence of the HCV HVR1 from this asymptomatic carrier altered with time, as seen in patients with CH. Alterations of amino acids in the HVR1 were correlated with persistent HCV infection rather than with clinical symptoms. Sequence heterogeneity of HVR1 was not correlated with alanine aminotransferase (ALT) values or liver histological findings. The necessity of clinical follow-up of HCV asymptomatic carriers is discussed.
Adult↗
Interleukin-2 expanded tumor-infiltrating lymphocytes and their response to preoperative alpha-interferon in patients with renal cell carcinoma.
To determine whether interferon-alpha could augment antitumorigenic effect of the tumor-infiltrating lymphocytes expanded with interleukin-2, we evaluated the properties of interleukin-2 expanded tumor-infiltrating lymphocytes in 24 patients with renal cell carcinoma with or without treatment with interferon-alpha. Tumor-infiltrating lymphocytes containing tumor cells were separated from nephrectomy specimens by enzymatic digestion and Percoll gradient centrifugation, and were cultured in the serum-free medium containing interleukin-2. The number of lymphocytes increased by 10 to 1,000-fold by day 28 of culture. There was no difference in the proliferation of tumor-infiltrating lymphocytes between interferon-alpha treated patients and controls. On day 14 tumor-infiltrating lymphocytes in the treated patients contained significantly more activated cells (HLA-DR+) and suppressor T cells (CD8+11+) than those in the controls. No significant difference was noted, however, in the cytotoxicity of tumor-infiltrating lymphocytes against autologous and allogenic renal cell carcinoma, K-562 or Daudi cells between the experimental and control groups on day 14 or 28. No specific effects on the major histocompatibility antigens, such as modulation of the expression attributable to the preoperative treatment with interferon-alpha, were observed on renal cell carcinoma tissue when determined by immunohistochemical staining. These findings suggest that interferon-alpha does not consistently produce a beneficial effect on interleukin-2 expanded tumor-infiltrating lymphocytes in patients with renal cell carcinoma.
Adult↗
Anti-AIDS agents, 11. Betulinic acid and platanic acid as anti-HIV principles from Syzigium claviflorum, and the anti-HIV activity of structurally related triterpenoids.
Betulinic acid [1] and platanic acid [2], isolated from the leaves of Syzigium claviforum, were found to be inhibitors of HIV replication in H9 lymphocyte cells. Evaluation of anti-HIV activity with eight derivatives of 1 revealed that dihydrobetulinic acid [3] was also a potent inhibitor of HIV replication. The C-3 hydroxy group and C-17 carboxylic acid group, as well as the C-19 substituents, contribute to enhanced anti-HIV activity. The inhibitory activity of these compounds against protein kinase C (PKC) was also examined, since a correlation between anti-HIV and anti-PKC activities has been suggested. However, there was no apparent correlation between anti-HIV activity and the inhibition of PKC among these compounds.
Antiviral Agents↗
Renin inhibitor: transport mechanism in rat small intestinal brush-border membrane vesicles.
The transport characteristics of the renin inhibitor ((3S,4S)-4-[N-morpholinoacetyl-(1-naphthyl)-L-alanyl-N-methyl-(4-t hiazolyl)-L- alanyl]amino-3-hydroxy-5-cyclohexyl-1-(4-pyridyl)-1-pentanone; CH3-18) in rat small intestinal brush-border membrane vesicles (BBMV) were examined by a rapid filtration technique. The uptake of CH3-18 was markedly stimulated by an inwardly directed H+ gradient (pH 7.5 inside, pH 5.5 outside) and showed an uphill transport. It was competitively inhibited by tripeptides and tetrapeptides, but not by amino acids or dipeptides. A countertransport effect on the uptake of CH3-18 was observed in the vesicle preloaded with a tripeptide. Effects of the fragments of several renin inhibitors were evaluated by their inhibitory and countertransport effects on the uptake of CH3-18. The morpholino group at the N-terminal was found to be important for the uptake of CH3-18.
Amino Acid Sequence↗
Renin inhibitor: relationship between molecular structure and oral absorption.
Common problems in developing renin inhibitors are low solubility, insufficient oral absorption, and fast hepatic clearance. We focused on the molecular structure of renin inhibitors to overcome these problems. Cyclodextrins (CD) improved the low solubility of renin inhibitors, with beta-CD showing the best ability to dissolve renin inhibitors. The intestinal absorption of renin inhibitors varied with both their solubility and molecular structure. Coadministration of beta-CD improved the intestinal absorption of some renin inhibitors with low solubility as measured by transport into the mesenteric vein in the absorption experiment using the rat intestinal loop. Substitutions at both the N and C terminals was essential for absorption from the small intestine. A naphthyl group at the N-terminal further improved intestinal absorption. A carrier system appeared to be involved in the intestinal absorption of some renin inhibitors. N-methylation at the amide bond of thiazolylalanine suppressed the high hepatic clearance of one of the test compounds 18 which was well absorbed from the small intestine and it improved its oral bioavailability.
Animals↗
Combination of lymphokine-activated killer cells and interleukin-2 in treating metastatic renal cell carcinoma.
OBJECTIVE: To study the properties of lymphokine-activated killer (LAK) cells and the effect of immunotherapy with a combination of autologous LAK cells and interleukin-2 (IL-2) [LAK therapy] in 10 patients with metastatic renal cell carcinoma (RCC). MATERIALS AND METHODS: The LAK cells were generated from peripheral blood lymphocytes (PBL) by incubation in a serum-free medium (AIM-V) supplemented with IL-2 for 4 days and killer cells were administered intravenously twice a week. The LAK cells showed cytotoxicity against allogenic RCC cell lines and augmented NK and LAK activities. Their phenotypes were CD25+, HLA-DR+, CD3+, and CD16+. Furthermore, LAK cells released IFN-gamma, IL-1 beta, and TNF-alpha. The total number of LAK cells administered ranged from 3.8 x 10(9) to 52.6 x 10(9) cells and the total amount of IL-2 ranged from 150 x 10(5) to 900 x 10(5) U. The effect on pulmonary metastasis in response to LAK therapy was studied. RESULTS: The outcome was complete response (1), partial response (1), minor response (2), no change (4) and disease progression (2). Toxic effects were transient and no serious side-effects occurred. Evaluation of host immune parameters indicated that a clinical response was expected in patients with increasing proportions of CD16+, CD25+, CD57+, HLA-DR+ and CD3+DR+ cells among PBL and with augmentation of NK and LAK activities. Brain metastases were detected in three patients during or after treatment. CONCLUSION: LAK therapy appears to be effective in treating some patients with RCC and pulmonary metastasis. The potential for inducing brain metastasis, however, should be taken into account.
Aged↗