Phase II Study of Oral Administration of 5'-Deoxy-5-Fluorouridine (5'-DFUR) for Solid Tumors

A phase II trial of 5'-deoxy-5-fluorouridine (5'-DFUR), a newfluorinated pyrimidine analog which has been demonstrated tohave potential superiority over 5-FU and tegafur for chemotherapyof murine tumors, was performed in patients with advanced non-smallcell carcinoma of the lung and metastatic pulmonary tumors.5'-DFUR at a dose of 800 mg/m² was given per os every day formore than four weeks. None of 15 evaluable patients with non-smallcell carcinoma of the lung and 15 evaluable patients with metastaticpulmonary tumors showed a complete or partial response. Toxiceffects of 5'-DFUR included anorexia (29%), diarrhea (26%),nausea (23%), vomiting (10%), leukocytopenia (10%), generalfatigue (10%), liver disorder (6%) and thrombocytopenia (6%). ^**Present address: Third Department of Internal Medicine, Schoolof Medicine, Toku-shima University, Kuramoto-cho 3-chome, Tokushima770, Japan.     

Clinical significance of hepatitis G virus infection in patients on long-term haemodialysis

Infection with the newly discovered hepatitis G virus (HGV) was analysed in 163 patients on long-term haemodialysis to clarify its prevalence and clinical significance. Hepatitis G virus RNA in serum was measured by polymerase chain reaction with primers corresponding to the putative non-structural 5’ region. Of the 163 patients, three (1.8%) were positive for hepatitis B surface antigen, 40 (24.5%) were positive for hepatitis C virus (HCV)-RNA and 16 (9.8%) were positive for HGV-RNA. Five of the 16 patients with HGV-RNA were also positive for HCV-RNA. Patients with HCV and HGV coinfection had undergone a longer duration of haemodialysis (P=0.001) and had higher units of transfusion (P=0.031) compared with those without hepatitis virus infection. Transfusion history was significantly higher (P=0.039) in patients with only HGV infection than in those without hepatitis virus infection. Hepatitis C virus RNA concentration was higher (P=0.032) in patients with HCV and HGV coinfection than in those with HCV infection only, but alanine aminotransferase (ALT) levels were similar between these two groups. In conclusion, about 10% of patients on haemodialysis were infected with HGV and the infection was closely associated with transfusion history.     

Serum Glycoprotein Profile before and after Radical Surgery in a Case of Giant Cell Carcinoma of the Lung

Profiles of serum glycoproteins ₁-acid glycoprotein (₁-AG),₂-HS-glycoprotein (₂-HS), ß₂-glycoprotein I (ß₂-G),haptoglobin (HP), hemopexin (HX), and prealbumin (PA) alongwith the concentration of sialic acid were followed sequentiallyin a case of giant cell carcinoma of the lung, before and afterradical surgery. Before surgery, ₁-AG levels in the serum ranged from 2.1 to2.7 times the upper limit of the normal range. However, in contrastwith the usual mode of reaction of these kinds of proteins,the serum concentration of ₁-AG failed to increase after surgeryand showed a progressive fall after the 7th postoperative day.Concentrations of ₂-HS showed a significant elevation aftersurgery. ß₂-G showed a slight increase over normalbefore surgery but showed no consistent changes as a resultof surgery. HP levels in serum fell progressively to the normalrange during the course of this study, irrespective of surgery.The levels of PA in the serum were subnormal preoperativelybut gradually increased to the normal range after surgery. Theserum sialic acid concentration closely paralleled that of HPor ₁-AG. Analytical isoelectric focusing in polyacrylamide gel,from pH 2.9 to 5.0, was carried out for serum acid proteins.There was a tendency toward a gradual preoperative increaseand postoperative decrease in the acidic component.     

Preliminary Phase II Study of 1-(2-Chloroethyl)-3-(MethylAlpha-D-Glucopyranos-6-Yl)-1-Nitrosourea (MCNU) Against Primary Lung Cancer and Metastatic Pulmonary Tumors

A phase II study of 1-(2-chloroethyl)-3-(methyl--D-glucopyranos-6-yl)-1-nitrosourea(MCNU) was conducted with 16 patients with primary lung canceror metastatic pulmonary tumors who had failed to respond toconventional therapy. MCNU was administered by a single intravenousinjection at a dose of 120 mg/m². There were no patients whoshowed any objective responses. Although stabilization was achievedin 12 patients, four patients with primary lung cancer experiencedprogressive disease. Gastrointestinal toxicities such as anorexia,nausea and vomiting were mild or moderate and readily subsidedwithout any treatment. The major toxic side effects were leukocytopeniaand thrombocytopenia. Five patients (38.4%) had leukocytopeniaof less than 2,000/mm³ and six patients (46.1%) had thrombocytopeniaof less than 5.0x10⁴/mm³.     

ANGIOTENSIN II BLUNTS, WHILE AN ANGIOTENSIN-CONVERTING ENZYME INHIBITOR AUGMENTS, REFLEX SYMPATHETIC INHIBITION IN HUMANS*

1. The role of angiotensin (Ang)II in and the effects of angiotensin-converting enzyme (ACE) inhibitors on the regulation of sympathetic neural activity were examined in humans. 2. We measured baseline values of muscle sympathetic nerve activity (MSNA) and its reflex inhibition in 28 patients with essential hypertension with elevated plasma renin activity (PRA; > 1.0 ng/mL per h = 0.28 ng/L per s) before and after either acute or chronic oral administration of an ACE inhibitor or placebo and in 20 normotensive subjects before and after infusion of either AngII (5 ng/kg per min = 4.8 pmol/kg per min) or vehicle (5% dextrose). Muscle sympathetic nerve activity was recorded from the tibial nerve and its reflex inhibition was evaluated during pressor responses to bolus injection of phenylephrine (2 micrograms/kg, i.v.). 3. Blood pressure was significantly decreased (P < 0.01) after the acute oral administration of captopril (25 mg), accompanied by a slight increase in MSNA in patients with essential hypertension compared with control patients who received placebo administration. Reflex changes in MSNA were significantly augmented after oral administration of captopril (-4.1 +/- 0.5 vs -6.2 +/- 0.6%/mmHg, respectively; P < 0.01), with a significant reduction of plasma AngII, while they were not affected by placebo administration. 4. In contrast, acute AngII infusion was accompanied by decreases in both PRA and MSNA in normotensive subjects. Reflex changes in MSNA were significantly reduced after AngII infusion (-11.0 +/- 0.8 vs -7.4 +/- 1.0%/mmHg, respectively; P < 0.01) but not after vehicle alone. 5. Chronic ACE inhibition by 12 week oral imidapril administration (5-10 mg/day) significantly (P < 0.05) decreased baseline values of MSNA, which were accompanied by a significant (P < 0.05) increase in the reflex inhibition of MSNA, while plasma concentrations of noradrenaline were unaffected. 6. These results indicate that AngII blunts reflex inhibition of sympathetic neural activity and that inhibition of the renin-angiotensin system by an ACE inhibitor augments reflex regulation of sympathetic neural activity and reduces baseline values in patients with essential hypertension.     

Laparoscopic management of urachal remnants in adulthood

BACKGROUND: The aim of this study was to investigate the outcome of laparoscopic excision of urachal remnants (LUR), and to compare the outcome with that of the traditional open excision of urachal remnants (OUR). METHODS: Between February 2001 and December 2005, six patients with a mean age of 23.8 years who had a symptomatic urachal sinus underwent radical LUR. Using 12 mm and 5 mm ports, the caudal stump of the urachus was ligated with an absorbable clip and divided. The peritoneal and preperitoneal tissue between the medial umbilical ligaments was dissected free of the transversalis fascia. Dissection was carried out along the preperitoneal plane toward the umbilicus. The cephalic side of the lesion was ligated at the umbilicus with an endo-loop and divided. In addition, four patients who underwent a traditional OUR were included. Peri- and postoperative records were reviewed to assess morbidity, recovery, and outcome. RESULTS: The operative duration was not significantly shorter for the LUR group than the OUR group, but there was generally a reduction in blood loss (mean 16.5 vs 68.3 mL), an earlier resumption of eating (mean 1.3 vs 2.5 days), and a shorter hospital stay (mean 5.3 vs 10.5 days). There were no intraoperative complications in either the LUR or the OUR group. Mean follow up was 5 (range 4-12) months. There were no postoperative complications. CONCLUSIONS: The results suggest that LUR can be safely and satisfactorily performed in adulthood.