In vitro contractile effects of neurokinin receptor blockade in the human ureter

PURPOSE: We identified the predominance of neurokinin-2 receptors and evaluated the inhibition of spontaneous contraction via the blockade of neurokinin-2 receptors in human ureteral segments. MATERIALS AND METHODS: Excess ureteral segments from human subjects undergoing donor nephrectomy or reconstructive procedures were suspended in tissue baths containing Krebs buffer. After spontaneous contractions were recorded, tissues were incubated with 1 microM. solutions of phosphoramidon and captopril (to inhibit peptide degradation) and either the neurokinin-1 receptor antagonist CP 99,994, the neurokinin-2 receptor antagonist SR 48,968, the neurokinin-3 receptor antagonist SR 142,801 or dimethyl sulfoxide (control) for 1 hour. Contraction magnitude and frequency were again recorded and compared with spontaneous levels. Concentration-response curves to the tachykinins substance P, and neurokinins A and B were determined in the presence and absence of antagonists. RESULTS: Neurokinin A increased contractility at lower concentrations than substance P or neurokinin B (p <0.013). Neurokinin-2 receptor blockade produced a 100-fold rightward shift of the concentration-response curves (p <0.013), while neurokinins 1 and 3 receptor blockade had no effect. SR 48,968 significantly reduced contractility during the 1-hour incubation period, causing a 97% reduction in spontaneous rates compared with a 29% reduction in control tissues. CP 99,994 and SR 142,801 had no significant effect. CONCLUSIONS: Neurokinin-2 is the predominant receptor subtype responsible for tachykinin induced contraction of human ureteral smooth muscle. In vitro treatment with the neurokinin-2 antagonist SR 48,968 reduces the spontaneous contraction rate by 97% in vitro. Neurokinin-2 receptor antagonists may have clinical applications for ureteral disease.     

Renal salvage procedure for synchronous bilateral Wilms' tumor

This report describes a renal salvage procedure performed in a 2-year-old girl with bilateral renal tumors comprising a multilocular, cystic tumor of the right kidney and a solid and cystic nephroblastoma of the left kidney after chemotherapy. Surgery was performed because the right kidney became hydronephrotic due to compression by the enlarged cysts, while the left tumor showed only minimal shrinkage even after three courses of chemotherapy. The right-sided cysts were simply unroofed and the left-sided tumor was extirpated by partial nephrectomy. Her postoperative course was uneventful with considerable recovery of the function of each kidney. This procedure should be considered if the pathological features of the tumor are relatively favourable. Accepted: 20 January 1999     

Anti-murine Antibody Response to Mouse Monoclonal Antibodies in Cancer Patients

Although development of human anti-murine inununoglobulin antibody (HAMA) is often seen in patients receiving murine antibodies, the variety of methods used for detecting HAMA makes it difficult to compare directly the HAMA responses measured by different assays. In the present study, several parameters of the HAMA response to two murine monoclonal antibodies were evaluated. The anti-sialosyl Tn antibody MLS102 and anti-CA125 antibody 145-9, which were labeled with ¹¹¹ln, were injected intravenously into 17 colorectal cancer patients and 11 ovarian cancer patients for immnnoscintigraphy, respectively. HAMA was measured by enzyme-linked immunosorbent assay. There was no difference in baseline HAMA levels before antibody injection between the two groups. HAMA developed more frequently in ovarian cancer patients receiving the 145-9 antibody than in colorectal cancer patients receiving the MLS102 antibody (9/11 vs. 6/17, P <0.05). No significant difference was observed in maximal HAMA levels between the two groups of patients. However, time to reach the maximal levels was delayed and the duration of the response seemed longer in ovarian cancer patients. Among 11 patients receiving the 145-9 antibody three patients became positive for HAMA more than 2 months after antibody injection and the other two had HAMA activity in their sera for more than 17 months. HAMA response was different between the two antibodies, and late onset or long duration of HAMA response against the 145-9 antibody suggests the importance of HAMA measurement in patients who receive a second injection of murine antibodies even after a long interval.     

A case of diffusely infiltrating carcinoma of the sigmoid colon associated with lymphangitis carcinomatosa effectively treated with sequential MTX.5-FU and 5'-DFUR

A 37-year-old man was diagnosed as having a diffusely infiltrating carcinoma of the sigmoid colon associated with lymphangitis carcinomatosa. Sequential methotrexate (MTX).5-fluorouracil (5-FU) therapy with oral administration of doxifluoridine (5'-DFUR) was started. After 9 cycles of the MTX.5-FU therapy (total dose: MTX = 900 mg/body, 5-FU = 7,500 mg/body), radiographic examinations showed a partial response in the primary and pulmonary lesion, and paraaortic lymph nodes. Histological evaluation of the resected specimen by Hartmann's operation showed a grade 2 effect in the primary lesion and metastatic lymph nodes. This chemotherapy was repeated postoperatively. The patient died of pulmonary disease, deteriorating rapidly 60 days postoperatively. Diffusely infiltrating carcinoma of the large-bowel is generally far advanced at the time of diagnosis. The results suggest that sequential MTX.5-FU therapy and oral administration of 5'-DFUR are worth performing in clinical trials for patients with diffusely infiltrating carcinoma of the large-bowel.     

Combination chemotherapy with irinotecan hydrochloride plus carboplatin for patients with advanced or recurrent colorectal cancer--a pilot study

A pilot study was performed to evaluate the feasibility and efficacy of irinotecan hydrochloride (CPT-11) plus carboplatin (CBDCA) for treatment of advanced or recurrent colorectal cancer. Fifteen patients with colorectal cancer (nonresectable, 1; noncurative resection, 5; recurrent disease, 9) were treated with CPT-11 (40-50 mg/m2) plus CBDCA (70-100 mg/m2) once a week for 2-3 weeks followed by a one-week rest. This treatment was repeated until disease progression or severe toxic effects were found. The total dose of CPT-11 ranged from 135 to 1,214 (median, 467) mg/m2 and that of CBDCA ranged from 267 to 2,022 (median, 933) mg/m2. Adverse effects included nausea (grade 2) in 2 (13.3%) diarrhea (grade 2) in 2 (13.3%), leukopenia (grade 3) in 2 (13.3%), thrombocytopenia (grade 1) in one (6.7%), and hair falling (grade 3) in one (6.7%). The response rate of 14 evaluable patients was 14.3% (CR, 1; PR,1; NC,7; PD,5). The median survival time of all patients was 405 days from the start of chemotherapy. The survival time of patients with CR, PR, and NC (n = 9) tended to be longer than that of those with PD (n = 5) (p = 0.06). The median time to disease progression was 105 days. These results suggest that this combination chemotherapy is feasible and effective in the treatment of advanced or recurrent colorectal cancer.     

A human T cell leukemia virus type-I carrier with recurrent thrombocytopenia and various autoantibodies.

A 34-year-old woman infected with human T cell leukemia virus type-I(HTLV-I) with recurrent thrombocytopenia and various autoantibodies is described. The platelet counts fluctuated between 1.3 x 10(4)/microliters and 14.8 x 10(4)/microliters without any medical treatment, and thrombocytopenia improved with a decrease of platelet-associated IgG (PA-IgG). Autoantibodies such as rheumatoid factor, antinuclear factor, anti-Sm, anti-RNP and anti-SSA antibodies were also recognized. Marker analysis of peripheral mononuclear cells showed an increase in the proportion of CD 25+ cells, CD 3+ HLA-DR+ cells, CD4+ HLA-DR+ cells and CD8+ HLA-DR+ cells. The recurrent thrombocytopenia and development of various autoantibodies in this HTLV-I carrier are speculated to be due to the alteration of B cell functions by T cells infected with HTLV-I.     

A case of tetralogy of Fallot with pulmonary aneurysm

A case of pulmonary artery aneurysm associated with tetralogy of Fallot is presented. A 28-year-old man was admitted for evaluation of cyanosis and cardiac murmur. Preoperative angiography revealed tetralogy of Fallot and an aneurysm of the main pulmonary artery aneurysm. Operation consisted of pulmonary artery aneurysmectomy and total correction of the tetralogy of Fallot. Microscopic examination of the resected aneurysm showed the thickening of intima and fragmented elastic fibers of media. A brief review of the literature emphasizes the necessity of the surgical intervention.