Carpentier-Edwards pericardial aortic valve in middle-aged patients comparison with the St. Jude medical valve

Objective The objective of the present study was to compare long-term results of single aortic valve replacement (AVR) with mechanical (St. Jude Medical valves: standard) and biologic (the Carpentier-Edwards pericardial) prostheses. Method: Between 1995 and 2002, 95 patients who underwent single AVR with mechanical (n=46) or biologic (n=49) prostheses were enrolled in this study. The mean age at the operation was 54.0±9.6 years (range: 20 to 69 years) with the mechanical and 68.8±7.1 years (range: 44 to 85 years) with the biologic prosthesis. Results: The 9-year actuarial survival rate, which was calculated by taking perioperative mortality into account, was 90.3±4.6% for patients with mechanical valves and 87.6 ±4.8% for patients with bioprostheses, with no difference between the two groups (p=0.342). The 9-year freedom rate from thromboembolism, reoperation, endocarditis was 94.8+3.6%, 100% and 97.8 ±2.2% for patients with mechanical valves and 98.0 ±2.0%, 97.5 ±3.4% and 95.0 ±3.4% for those with bioprostheses, respectively. After 9 years, freedom from cardiac death averaged 97.8% in the group with mechanical valves compared with 95.3% in those with bioprostheses (p=0.541). Conclusion: We conclude that the mid-term durability of the Carpentier-Edwards pericardial valve in the aortic position for the elderly is excellent. Nevertheless, the risk of tissue valve reoperation progressively increases with time, and a longer follow-up may be necessary to provide its value compared with the mechanical valves in a country like Japan with a high life expectancy. (Jpn J Thorac Cardiovasc Surg 2005; 53:465-469)     

Production of monoclonal antibodies against human bladder cancer cells and application to immunohistochemical analysis of bladder cancer

Two hybridomas secreting two monoclonal antibodies IgG1 B1.4 and IgG2a B1.6 were obtained by immunizing BALB/c mice with human bladder cancer cell line EJ-1. In immunohistochemical staining of cryopreserved tissues, B1.4 reacted with 0 of 9 grade 1 TCC, 6 of 11 grade 2, all of 6 grade 3 and five metastatic specimens. The antigen recognized by B1.4 was not expressed by normal urothelial cells but were expressed by vascular endothelial cells and muscle of tunica media. The target antigen of B1.6 was expressed by normal urothelial cells and all grade of TCC. In this study, it was demonstrated that poorly differentiated bladder cancer and metastatic specimens of bladder cancer express a vascular carbohydrate antigen. Taking the escape mechanism of immune surveillance, into consideration, it is possible that the antigen recognized by B1.4 is an indicator of metastatic potential of bladder cancer.     

IL-12 p40 prevents the development of chronic enterocolitis in IL-10-deficient mice

T-helper-1 (Th1) cytokines play an important role in Crohn's disease, and interleukin-12 (IL-12), which is composed of two subunits, p40 and p35, drives Th1 differentiation. In previous reports, IL-12 p40 was shown to prevent IL-12 from binding to the receptor. We demonstrate here the effect of IL-12 p40 overexpression in intestinal epithelia on enterocolitis mediated by Th1 cells in IL-10-deficient (IL-10(-/-)) mice on a C57BL/6J background. IL-10 deficient (IL-10(-/-))/T3b-IL-12 p40+ (IL-12 p40+) mice and IL-10(-/-)/T3b-IL-12 p40- (IL-12 p40-) mice were generated by crossing T3b-IL-12 p40 transgenic mice and IL-10(-/-) mice. At 8 weeks of age, IL-12 p40+ mice did not show any clinical manifestations of colitis. The colon length of IL-12 p40- mice became shorter than that of IL-12 p40+ mice. The histological score of IL-12 p40+ mice was lower. Interferon-gamma (IFN-gamma) production was suppressed in both the mesenteric lymph node cell culture and colon tissue culture of IL-12 p40+ mice. There was no significant difference in IL-4 production and tumor necrosis factor-alpha (TNF-alpha) production between the two groups. These results show that overexpression of IL-12 p40 in intestinal epithelia prevents enterocolitis in IL-10(-/-) mice by suppressing IFN-gamma production, and suggest a potential clinical application of IL-12 p40 for Crohn's disease. Furthermore, these results also suggest that local gene transduction in the intestinal epithelium may be a potent therapeutic approach for Crohn's disease.     

Blood flow velocity in the common carotid artery in humans during graded exercise on a treadmill

Cerebral blood volume flow and flow velocity have been reported to increase during dynamic exercise, but whether the two increase in parallel and whether both increases occur as functions of exercise intensity remain unsettled. In this study, blood flow velocity in the common carotid artery was measured using the Doppler ultrasound method in eight healthy male students during graded treadmill exercise. The exercise consisted of stepwise progressive increases and decreases in exercise intensity. The peak intensity corresponded to approximately 85% of maximal oxygen consumption. During this exercise, the heart rate (f _c), mean blood pressure (BP) in the brachial artery and mean blood flow velocity (_cc) in the common carotid artery increased as functions of exercise intensity. At the peak exercise intensity, (f _c), BP and _cc increased by 134.5%, 20.5% and 51.8% over the control levels before exercise (P < 0.01), respectively. The resistance index (RI) and pulsatility index (PI) were determined from the velocity profile and were expected to reflect the distal cerebral blood flow resistance. The RI and PI increased during the graded exercise, but tended to decrease at the highest levels of exercise intensity. As _cc increased with increases in exercise intensity it would be expected that cerebral blood flow would also increase at these higher intensities. It is also suggested that blood flow velocity in the cerebral artery does not proportionately reflect the cerebral blood flow during dynamic exercise, since the cerebral blood flow resistance changes.     

Mutagenicity of the bile of dogs with an experimental model of an anomalous arrangement of the pancreaticobiliary duct

To learn the reasons for the high incidence of biliary carcinomain patients with anomalous arrangement of the pancreaticobiliaryduct (APBD) mutagenicity of the bile of APBD-modeled dogs thathad received a dorsal pancreatico-cholecystostomy was assayedby the Ames Salmonella mutation test. The bile from two outof 18 APBD dogs was mutagenic for Salmonella typhimurium strainTA98 under the condition of metabolic activation by rat liverS9 fraction, while the bile from 17 normal dogs was not mutagenic.Furthermore, the bile from five APBD dogs i.p. administered1-nitropyrene (1-NP), which is a typical environmental mutagen,was more mutagenic for strain TA98 than that from 1-NP-treatednormal dogs. The bile from the APBD dogs had very high amylaseactivity, indicating that the bile contained pancreatic juiceas a result of the pancreatico-cholecystostomy. When pancreaticjuice from a normal dog was added to the bile from 1-NP-treatednormal dogs, mutagenicity of the bile increased 1.6- to 2.0-fold.Furthermore, sulfatase increased the mutagenic activity of thebile in the presence of the pancreatic juice. HPLC revealedthat the bile from a 1-NP-treated APBD dog contained mutagenic1-nitro-6/8-hydroxypyrene and 1-nitro-3-hydroxypyrene, whilebile from a 1-NP-treated normal dog did not contain these deconjugatedproducts. The pancreatic juice from a normal dog had very high-glutamyltransferase (GGT) and aminopeptidase activities andlow sulfatase activity, but it had no ß-glucuronidaseactivity. In addition, the bacteria that easily infect the biliaryduct of APBD dogs, Escherichia coli, Klebsiella, Enterobacterand Proteus, had high ß-glucuronidase activity. Inparticular, Klebsiella showed a very high sulfatase activity.These results suggest that pancreatic juice enzymes and bacteriainfecting the biliary duct deconjugate the detoxified mutagensin the bile and induce mutagenicity of the bile from APBD dogsor APBD patients.     

Health status of male preparatory school students lodging at a dormitory in Japan

An investigation on the health status of 79 male preparatory school students lodging at a dormitory in Japan was carried out by questionnaire on lifestyles, subjective symptoms and mental status, as compared with two control groups: 73 medical students and 36 new employees. About 83 % of them slept less than 6 hours and 70 % of them did not exercise. Many students are troubled with back pain or lumbago(47%), sensation of incomplete bladder emptying(l6%), loss of visual acuity(55%) and eye fatigue(65%). Self-rating depression scale score of preparatory school students was not significantly higher than those of the control groups. The lifestyles of preparatory school students found to be very restricted and strained. However, no significant differences on mental adverse health effects was found among three groups.     

A multivariate analysis of prognostic factors related to recurrence and progression of superficial bladder cancer

Prognostic factors related to the recurrence and progression of superficial primary bladder cancers were analyzed by Cox's proportional hazards regression model. We followed 75 patients (stage Ta, 49 cases; T1, 26 cases; grade G1, 42 cases; G2, 29 cases; G3, 4 cases) after transurethral resection for 10 to 74 months (median 38 months). The antibodies reactive with the products of oncogenes [anti-c-myc oncoprotein (MYC-1); anti-c-erbB-2 oncoprotein], tumor suppressor gene [anti-p53 mutant protein (BP53-12)], growth factor receptor [anti-transferrin receptor (HBT-2)], proliferation [anti-proliferatioe nuclear antigen (Ki-67)], and malignant transformation (B1.4) were used for immunohistochemical staining. The reactivities of mAb B1.4, HBT2, and BP53-12 were significantly increased according to the grade, and those of mAb Ki-67, MYC-1, and c-erbB-2 were not. The reactivities of all antibodies were not significantly different between stages Ta and T1. As prognostic factors, stage, grade, tumor number, urinary cytology, and reactivities of the above six antibodies were used for the analysis. Urinary cytology, multifocality, and the reactivity of mAb Ki-67 showed a relative but significant high risk for recurrence, and the reactivities of mAb HBT2, mAb B1.4, and mAb Ki-67 showed a significant high risk for progression in the multivariate analysis. These results suggest that mAb B1.4 may be useful as a new prognostic factor for the progression of superficial bladder cancer.     

Adjunctive value of cell proliferation but not of apoptosis to interpret pathologic effects on prostatic cancer after neoadjuvant endocrine therapy

BACKGROUND: The current histological evaluation of the effects of endocrine therapy has difficulty in distinguishing pathologic degeneration caused by androgen ablation from residual poorly differentiated tumor. Therefore, we examined the changes in cell proliferation and apoptosis before and after endocrine therapy and analyzed whether they correlated with pathologic effects and histological differentiation. METHODS: Between January 1986 and December 1995, 52 patients with clinical stage B2 and C prostate cancer underwent radical prostatectomy after neoadjuvant endocrine therapy (median duration 3.8 months). Proliferative and apoptotic activities of pretreatment biopsy specimens and radical prostatectomy specimens were analyzed with MIB-1 monoclonal antibody and in situ end-labeling of fragmented DNA. RESULTS: The mean proliferative index (PI) of radical prostatectomy specimens was significantly lower than that of biopsy specimens (P = 0.000003) and the decrease in PI after endocrine therapy was significantly related to histological differentiation (P = 0.014). There was a weak relationship between the decrease in PI after endocrine therapy and pathologic effects (P = 0.054), while in pathologically effective cases (Grades 2 and 3), three out of 16 (19%) showed a < 50% decrease in PI after endocrine therapy, and may be regarded as having poorly differentiated tumors. The mean apoptotic index (AI) of prostatectomy specimens tended to be higher than that of biopsy specimens (P = 0.054). The increase in AI after endocrine therapy was not related to histological differentiation and pathologic effects. CONCLUSION: Pathologic effects caused by endocrine therapy may be in part misled by routine histopathologic staining and the change in PI may help in recognizing the pathologic effects of endocrine therapy and have adjunctive value for the interpretation of the effects of endocrine therapy.