Possible correlation between low antigenic drift of A(H1N1) influenza viruses and induction of HI antibodies

This study examined whether, during a seven-year period of low A(H1N1) influenza virus antigenic drift (1988–1989 and 1994–1995, winters), humoral antibody response of elderly volunteers to influenza vaccines could suggest a lack of antibody pressure for drift. In all the years studied A/Taiwan/1/86, the A(HIN1) vaccine component, had a low ability to induce protective hemagglutination-inhibiting (HI) antibody titres ( 1:40). However a similar low immunogenicity was found for some of the different A(H3N2) strain variants of influenza virus, co-circulating in the same period and showing a regular extent of antigenic variations.Although our data could be at least in part explained by the type of study population (elderly and repeatedly vaccinated), postepidemic serological studies did not evidence a consistently lower ability in mounting protective immune response in elderly people as compared with younger against the influenza strains studied. Therefore, our present results did not exclude a true low immunogenicity of A/Taiwan and of some A(H3N2) influenza strains, circulating in the winters examined. This suggests that, besides the necessity to evade prior immunity, additional factors could influence the frequency of influenza viruses antigenic drifts.Abbreviation HI hemagglutination inhibiting     

Gastroduodenal response to low-dose glucagon

A prospective, double-blind clinical study of the double-contrast upper gastrointestinal examination involving 240 patients was performed using glucagon in doses from 0.025 to 0.125 mg, in 0.025 mg increments. Although motility was diminished, neither gastric distension or coating was improved with the use of glucagon. However, duodenal distension and coating were markedly enhanced. The response of the pylorus was individualistic. The pylorus remained patent in most patients, and glucagon would not prevent barium spillage in the duodenum. However, in those patients with a "competent" pylorus, increasing glucagon doses produced a delay in gastric emptying. Several other variables, including weight, age, and gender, were studied and were not believed to be of clinical significance. Spontaneous gastroesophageal reflux was also increased with the use of glucagon. Glucagon mainly enhanced duodenal visualization but had no beneficial effect on the stomach or pylorus. Absolute dose is the most important factor, and all observable changes can be seen once a certain threshold dose (0.05 mg) is reached.     

Cyclooxygenase-2 activation mediates the proangiogenic effect of nitric oxide in colorectal cancer.

PURPOSE: Up-regulation of both inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) enzymes has been reported in colorectal cancer. We aimed at evaluating the possible interaction between the nitric oxide and COX-2 pathways, and its effect on promoting tumor angiogenesis. EXPERIMENTAL DESIGN: Expression of iNOS, COX-2, vascular endothelial growth factor (VEGF), and CD31 was analyzed in tumor samples and corresponding normal mucosa obtained from 46 surgical specimens. We also evaluated iNOS activity, prostaglandin E(2) (PGE(2)), cyclic GMP and cyclic AMP production in the same specimens. Nitrite/nitrate levels, and PGE(2) and VEGF production were assessed in HCT116 and HT29 colon cancer cell lines after induction and selective inhibition of the two enzyme pathways. RESULTS: A significant correlation was found between iNOS and COX-2 immunohistochemical expression. PGE(2) production significantly correlated with iNOS activity and cGMP levels. A significant correlation was also found among PGE(2) production, microvessel density, and VEGF expression. Coinduction of both iNOS and COX-2 activities occurred after lipopolysaccharide (LPS) and epidermal growth factor (EGF) treatment in HCT116 and HT29 cells. Inhibition of iNOS by 1400W significantly reduced both LPS- and EGF-induced PGE(2) production. Treatment with LPS, EGF, and arachidonic acid significantly increased VEGF production in the iNOS-negative/COX-2-positive HT29 cells. This effect was completely reversed by treatment with the selective COX-2 inhibitor celecoxib. CONCLUSIONS: Our data showed a prominent role of nitric oxide in stimulating COX-2 activity in colorectal cancer. This interaction is likely to produce a cooperative effect in promoting angiogenesis through PGE(2)-mediated increase in VEGF production.     

Bone marrow micrometastases in 109 breast cancer patients: Correlations with clinical and pathological features and prognosis

Background: The presence in bone marrow of cells which react with monoclonal antibodies against tumor-associated antigens has been proposed over the last few years as a new prognostic factor in breast cancer patients. Patients and methods: Bone marrow aspirates were obtained from 109 stage I and II breast cancer patients during or 2–4 weeks after primary surgery. The samples were processed for leukocyte separation on a Ficoll-Hypaque gradient and then used to prepare cytospin slides for immunocytochemical analysis. The slides were stained with a pool of monoclonal antibodies (MoAbs) which recognize tumor associated antigens, using the alkaline phosphatase anti-alkaline phosphatase method. The median follow-up was 36 months (range 15–62); 22 patients relapsed and 7 died. Results: Thirty-four of the 109 patients (31.1%) had MoAb positive bone marrow cells. The bone marrow was positive in 28/74 (37.9%) patients who had the aspirate taken during surgery and in 6/35 (17.1%) who had it taken after surgery (p = 0.055). No association was found between bone marrow positivity and tumour size, nodal status, menopausal status, estrogen receptor positivity or the proliferative index. No association was found between bone marrow and prognosis: the log-rank test was 0.291 (p > 0.5) for OS and 0.023 for DFS; the hazard ratio (positive vs negative) was 1.51 for OS (95% CI: 0.33–6.86) and 0.93 for DFS (95% CI: 0.35–2.45). Conclusions: In our series, bone marrow positivity did not correlate with prognostic parameters or prognosis. Of interest is the relative excess of positivity when the bone marrow was obtained during surgery.     

The role of bladder catheterization in total knee arthroplasty

The use of a urinary bladder catheter in the perioperative period for patients undergoing total knee arthroplasty is controversial. In the current study, two bladder management protocols were studied. One group of patients had an indwelling catheter inserted into the bladder before total knee arthroplasty. The other group of patients was observed and treated for urinary retention as necessary. From 1993 to 1998, 652 patients undergoing primary, unilateral total knee arthroplasty were randomized by surgeon into two groups: one group underwent preoperative insertion of an indwelling bladder catheter (306 patients), and one group (346 patients) had a catheter inserted postoperatively as necessary. Sixty-six percent (229 of 346) of these patients required catheterization (203 had indwelling catheters and 26 had intermittent straight catheters). A urinary tract infection developed in five patients (1.6%) in whom a catheter was inserted preoperatively. A urinary tract infection developed in six patients (1.7%) in whom a catheter was inserted if necessary. Five of these urinary tract infections developed in patients with delayed indwelling bladder catheters. A urinary tract infection did not develop in any patient in whom a straight catheter was inserted. There was no significant difference in the length of stay in the hospital between the two groups. The group in whom a catheter always was inserted generated $491 greater cost for total knee arthroplasty than patients in whom a catheter was inserted if necessary.     

Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer.

PURPOSE: To compare long-term survival in patients with locally advanced or metastatic transitional cell carcinoma (TCC) of the urothelium treated with gemcitabine/cisplatin (GC) or methotrexate/vinblastine/doxorubicin/cisplatin (MVAC). PATIENTS AND METHODS: Efficacy data from a large randomized phase III study of GC versus MVAC were updated. Time-to-event analyses were performed on the observed distributions of overall and progression-free survival. RESULTS: A total of 405 patients were randomly assigned: 203 to the GC arm and 202 to the MVAC arm. At the time of analysis, 347 patients had died (GC arm, 176 patients; MVAC arm, 171 patients). Overall survival was similar in both arms (hazard ratio [HR], 1.09; 95% CI, 0.88 to 1.34; P = .66) with a median survival of 14.0 months for GC and 15.2 months for MVAC. The 5-year overall survival rates were 13.0% and 15.3%, respectively (P = .53). The median progression-free survival was 7.7 months for GC and 8.3 months for MVAC, with an HR of 1.09. The 5-year progression-free survival rates were 9.8% and 11.3%, respectively (P = .63). Significant prognostic factors favoring overall survival included performance score (> 70), TNM staging (M0 v M1), low/normal alkaline phosphatase level, number of disease sites (相似文献