PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Dissemination”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 163 records · Page 9Linked to original sources

Generalized synthesis of evidence and the threat of dissemination bias. the example of electronic fetal heart rate monitoring (EFM).

Assessment of the potential impact of dissemination bias is necessary for meta-analysis. When evidence is available from studies of different designs, the different study types may be affected by dissemination bias to differing degrees. The evidence relating to electronic fetal heart rate monitoring (EFM) for preventing perinatal mortality is used to explore the feasibility of carrying out a dissemination bias assessment in a generalized synthesis of evidence (gse) framework. Visual inspection of funnel plots, statistical tests, and methods to "adjust" the results of a meta-analysis are all used in an extensive sensitivity analysis. The potential impact of dissemination bias on gse models synthesizing all the evidence together is also reported. Detailed consideration is given to the influence of meta-analysis model choice, and outcome scale used. Using the risk difference scale, funnel plots of the observational studies appeared highly asymmetric. However, further explorations show these conclusions are not robust over use of different outcome measures or different meta-analysis models. Researchers should be aware that dissemination bias may affect different sources of evidence differently. Although assessments such as those described here are recommended, awareness of their lack of robustness to outcome scale and model choice is important. Further research into methods to assess dissemination bias that are invariant to these factors is needed.

Cardiotocography↗

Marked difference in pathophysiology between tissue factor- and lipopolysaccharide-induced disseminated intravascular coagulation models in rats.

OBJECTIVE: Tissue factor and lipopolysaccharide frequently have been used to induce disseminated intravascular coagulation in experimental animal models. Although the pathophysiology of disseminated intravascular coagulation may differ according to the agents used to induce it, these previous models have not distinguished between the use of different disseminated intravascular coagulation-inducing agents. In this study, we attempted to evaluate the characteristic features of these agents in two types of disseminated intravascular coagulation models, with special reference to selected hemostatic parameters and pathologic findings in the kidney. DESIGN: Prospective, comparative, experimental study. SETTING: Laboratory at a university hospital. SUBJECTS: Twenty-seven male Wistar rats, age 6-7 wks, weighing 160-170 g. INTERVENTIONS: Three groups of animals were studied: a control group (n = 8) receiving physiologic saline, a tissue factor-treated group (n = 11) receiving tissue factor 3.75 units/kg, and a lipopolysaccharide-treated group (n = 8) receiving lipopolysaccharide 30 mg/kg; each group sustained infusion for 4 hrs via the tail vein. MEASUREMENTS AND MAIN RESULTS: The degree of hemostatic activation in both types of experimental disseminated intravascular coagulation was identical, based on the results of thrombin-antithrombin III complex levels. Markedly elevated D-dimer concentrations were observed without organ dysfunction or fibrin deposition in the kidney on administration of tissue factor, whereas markedly elevated plasminogen activator inhibitor activity, decreased antithrombin III activity, severe organ failure, and marked fibrin deposition in the kidney were observed for lipopolysaccharide administration. CONCLUSION: Because pathophysiology differed remarkably between the tissue factor- and lipopolysaccharide-induced disseminated intravascular coagulation models in rats, we recommend that they be assessed carefully as distinct entities to determine implications of their experimental and clinical use.

Animals↗

Guiding health promotion efforts with urban Inuit: a community-specific perspective on health information sources and dissemination strategies.

OBJECTIVE: To develop a community-specific perspective of health information sources and dissemination strategies of urban Inuit to better guide health promotion efforts. METHODS: Through a collaborative partnership with the Tungasuvvingat Inuit Family Resource Centre, a series of key informant interviews and focus groups were conducted to gather information on specific sources of health information, strategies of health information dissemination, and overall themes in health information processes. FINDINGS: Distinct patterns of health information sources and dissemination strategies emerged from the data. Major themes included: the importance of visual learning, community Elders, and cultural interpreters; community cohesion; and the Inuit and non-Inuit distinction. The core sources of health information are family members and sources from within the Inuit community. The principal dissemination strategy for health information was direct communication, either through one-on-one interactions or in groups. CONCLUSION: This community-specific perspective of health information sources and dissemination strategies shows substantial differences from current mainstream models of health promotion and knowledge translation. Health promotion efforts need to acknowledge the distinct health information processes of this community, and should strive to integrate existing health information sources and strategies of dissemination with those of the community.

Canada↗

Fibrinopeptide A in liver cirrhosis: evidence against a major contribution of disseminated intravascular coagulation to coagulopathy of chronic liver disease.

To test the hypothesis that disseminated intravascular coagulation contributes to hemostatic failure in liver cirrhosis, fibrinopeptide A and fibrin(ogen) degradation fragment E were measured in 69 patients with stable liver cirrhosis and compared with fibrinopeptide A and fibrin(ogen) degradation fragment E in 32 healthy subjects, 33 patients with thromboembolism, and 10 patients with hypofibrinogenemic disseminated intravascular coagulation. Mean fibrinopeptide A in cirrhosis was slightly increased compared with healthy subjects (2.4 vs. 1.8 ng/ml, p < 0.005), but fourfold lower than in thromboembolism (mean fibrinopeptide A 9.7 ng/ml; p < 0.0001), and tenfold lower than in disseminated intravascular coagulation (mean FPA 24.3 ng/ml; p < 0.0001). Single fibrinopeptide A levels in cirrhosis were within the normal range in 75% of the patients, marginally increased in 9%, and definitely increased in 16%. A definite increase in both fibrinopeptide A and fibrin(ogen) degradation fragment E, which characterized the groups of patients with thromboembolism and disseminated intravascular coagulation, was found in 10% of the cirrhotic patients. Among 17 patients with cirrhosis and hypofibrinogenemia, mean fibrinopeptide A (2.7 ng/ml) was tenfold lower compared with mean fibrinopeptide A in patients with hypofibrinogenemic disseminated intravascular coagulation (p < 0.0001), whereas the frequency of increased single fibrinopeptide A levels (29%) was not significantly different compared with the 52 cirrhotic patients without hypofibrinogenemia (single levels elevated in 23% of the cases). Moreover, the frequency of hypofibrinogenemia, thrombocytopenia, or abnormal clotting times was not significantly different in cirrhotic patients with normal fibrinopeptide A level when compared with cirrhotic patients with increased fibrinopeptide A. These findings do not support an important contribution of disseminated intravascular coagulation to coagulopathy of liver cirrhosis.

Adult↗

Disseminated intravascular coagulation and refractory shock induced by splanchnic metabolic acidosis.

In eight dogs, acidosis was induced by the infusion of lactic acid into the superior mesenteric artery in a dose of 5.0 to 12.5 millimoles per kilogram during a 30 minute period. Four dogs out of five in which the lowest pH of arterial blood was lower than 7 developed a typical acute disseminated intravascular coagulation, accompanied by a sudden elevation of arterial and portal venous pressure. In these four dogs, refractory shock developed between 0.5 and five hours after lactic acid infusion. The other four without disseminated intravascular coagulation maintained a normal blood pressure and survived until sacrifice six hours after infusion. In two dogs, systemic infusion of 10 millimoles per kilogram was performed in the same interval as the former. Both died from cardiac failure without occurrence of disseminated intravascular coagulation before the infusion was completed. The dogs with disseminated intravascular coagulation revealed a marked deterioration of coagulative system and generalized thrombi in the intestine, liver, lung and kidney. Minimal changes in these parameters were observed in the dogs without disseminated intravascular coagulation. The results suggest that the infusion of lactic acid into the superior mesenteric artery is a convenient model for the production of disseminated intravascular coagulation and resultant shock.

Acidosis↗

Total-body sequential segmental irradiation and combination chemotherapy for children with disseminated neuroblastoma.

Fourteen children with disseminated neuroblastoma were treated with segmental total-body irradiation and a combination of cyclophosphamide, vincristine and Adriamycin. Six others had localized tumors and were treated with either surgery alone or limited irradiation and chemotherapy. The main objective of the study was to find out if this aggressive therapy for disseminated neuroblastoma would be tolerated and would promote longer disease-free remissions and possibly, cures. Complete responses were obtained in all patients with localized tumors. Of the 14 patients with disseminated disease, three had complete responses, five had partial responses, two had objective responses, and four were classified as nonresponders. Survival rates for this group are poor. Only two patients are still alive, and the single patient who survives free of disease has had a complex clinical course that is only indirectly a result of treatment. The median survival for patients with disseminated tumor was 9 months, not appreciably different from earlier result. Although toxicity was clinically manageable, it interfered with the planned schedule of therapy. Continuous weight loss combined with severe bone marrow suppression due to irradiation prevented about 50% of the scheduled drug dose from being administered. This resulted in poor control of tumor outside of radiation ports and eventually led to progressive disease within previously irradiated sites. We conclude that irradiation used in this manner will not improve disease-free survival of children with disseminated neuroblastoma. It is essential that disseminated disease be controlled before extensive irradiation is attempted.

Antineoplastic Agents↗

The voluntary dissemination of performance information by health care organizations.

This paper examines the factors that influence the voluntary dissemination of performance information by health care organizations. A model of information dissemination is developed and tested using data on Health Maintenance Organizations. The empirical findings suggest that health care organizations disseminate information on their performance because there are collective-good benefits resulting from dissemination, particularly when the product or organizational innovation is unfamiliar to some purchasers. The findings also suggest that the competitive structure of the local health care market influences the dissemination decision, with health care organizations more likely to disseminate information about their performance in relatively competitive markets.

Catchment Area, Health↗

Gene therapy for intraperitoneally disseminated pancreatic cancers by Escherichia coli uracil phosphoribosiltransferase (UPRT) gene mediated by restricted replication-competent adenoviral vectors.

Although patients with unresectable pancreatic tumors have been treated with 5-fluorouracil (5FU)-based combination chemotherapy, the drug resistance of cancer cells presents a crucial therapeutic problem. It was reported that UPRT overcomes 5FU resistance. UPRT catalyzes the synthesis of 5-fluorouridine monophosphate (FUMP) from Uracil and phosphoribosylpyrophosphate (PRPP). The antitumor effect of 5FU is enhanced by augmenting 5-fluorodeoxyuridine monophosphate (FdUMP) converted from FUMP, which inhibits thymidylate synthetase (TS). We first demonstrated that injecting an E1-deficient adenoviral vector (Adv) expressing UPRT (AxCAUPRT) followed by 5-FU treatment resulted in a volume reduction of xenotransplanted human tumors. In examining the therapeutic effect of AxCAUPRT/5-FU against peritoneal dissemination, we found that non-selective gene transduction of AxCAUPRT caused severe adverse effects arising from the increase of F-dUMP in normal intestine. Because the therapeutic gene delivered by a restricted replication-competent Adv lacking 55 kDa E1B protein (AxE1AdB) is speculated to be expressed selectively in tumors, mice with established tumors were injected with AxE1AdB and E1-deleted Adv expressing the lacZ reporter gene (AxCAlacZ). The expression of the reporter gene (lacZ) was selectively enhanced in disseminated tumors. The therapeutic advantage of restricted replication competent Adv that expresses UPRT (AxE1AdB-UPRT) was evaluated in an intraperitoneal disseminated tumor model. To study the anti-tumor effect of AxE1AdB-UPRT/5FU, mice with disseminated AsPC-1 tumors were administered the Adv, followed by the 5FU treatment. It was shown that the treatment with AxE1AdB-UPRT/5FU caused a dramatic reduction of the disseminated tumor burden without toxicity in normal tissues. Our results showed that the AxE1AdB-UPRT/5FU system is a promising tool for intraperitoneal disseminated pancreatic cancer.

Adenoviridae↗

Enhanced efficacy of conditionally replicating herpes simplex virus (G207) combined with 5-fluorouracil and surgical resection in peritoneal cancer dissemination models.

BACKGROUND: The therapeutic efficacy of G207, a replication-competent herpes simplex virus, for malignancies is increased when combined with certain chemotherapies, but the mechanism is unclear and the interaction between G207 and surgical resection has not been extensively studied. The goals of the current study were to examine the performance of combination treatments for peritoneal disseminated cancers and to explore the mechanism of effective combinations. METHODS: Hamsters and SCID and BALB/c mice harboring peritoneal dissemination of gallbladder, gastric or colon cancer cells were treated with G207, 5-fluorouracil (5FU), or surgical resection alone, or G207 combined with 5FU or surgery. Animal survival, antiviral immunity, intratumoral ribonucleotide reductase activity, and viral spread were compared between the groups. RESULTS: The combination of G207 and 5FU prolonged the survival of hamsters bearing peritoneal dissemination of gallbladder cancer compared with the controls, G207 alone and 5FU alone. 5FU did not suppress the production of neutralizing antibodies against G207, but increased ribonucleotide reductase activity and viral spread in subcutaneous gallbladder tumors. The enhanced efficacy of the combination treatment was also observed in immunodeficient mice with disseminated gastric cancer. Although surgical resection did not significantly prolong animal survival or increase the intratumoral activity of ribonucleotide reductase, long-term survivors emerged from groups of animals treated with surgical resection and G207 for gallbladder and colon disseminated cancers. CONCLUSIONS: These results indicate that the increased activity of ribonucleotide reductase in tumors mediated by 5FU and the decreased tumor burden resulting from surgical resection may enhance the therapeutic efficacy of oncolytic herpes virus for peritoneal disseminated cancer.

Animals↗

Evaluation of an enhanced approach to the dissemination of the North American Guidelines for Children's Agricultural Tasks: a randomized controlled trial.

BACKGROUND: The North American Guidelines for Children's Agricultural Tasks were developed to assist farm parents in assigning developmentally appropriate and safe work to children aged 7 to 16 years. The purpose of this study was to compare the efficacy of the standard dissemination strategy with an enhanced, multiphased, dissemination approach in influencing parents to use/apply North American Guidelines for Children's Agricultural Tasks when assigning farm work to their children. METHODS: A multisite-randomized trial was performed. During 1999, 498 farms in Canada and the United States were enrolled. Enhanced dissemination activities included the provision of a video, personalized child development information, and supportive telephone calls. Follow-up with all farms occurred during the fall of 2000 to assess parental reaction to North American Guidelines for Children's Agricultural Tasks and to determine whether North American Guidelines for Children's Agricultural Tasks were actually used. RESULTS: Proportions of parents who were actively using North American Guidelines for Children's Agricultural Tasks at 15 months were 108/218 (49.5%) and 83/224 (37.1%) in the experimental and control groups, respectively (difference: 12.5%, 95% CI: 3.4, 21.7). Parental knowledge of the content of North American Guidelines for Children's Agricultural Tasks was also increased in the enhanced dissemination group. CONCLUSION: These results have important implications for dissemination of the North American Guidelines for Children's Agricultural Tasks resources. An enhanced dissemination strategy appears to increase the likelihood that North American Guidelines for Children's Agricultural Tasks will be used by farm parents.

Adolescent↗

[Value of cytokeratin and Ca 19-9 antigen in immunohistological detection of disseminated tumor cells in lymph nodes in pancreas carcinoma].

INTRODUCTION: Based on the fact that pancreatic carcinoma is still associated with poor outcome, the aim of the study was to determine frequency of early tumor cell dissemination using immunohistology in lymph nodes classified as tumor-free by conventional histopathology. METHODS: Fifteen patients with ductal pancreatic carcinoma and 10 patients with carcinoma of the papilla of Vater underwent radical tumor resection (resection status R0, tumor staging pTxpN0M0). In total, 229 lymph nodes classified as tumor-free by histopathology were investigated for disseminated tumor cells using antibodies against cytokeratin and CA19-9. As control, 81 lymph nodes obtained from patients with chronic pancreatitis were analyzed. RESULTS: In 55 of 229 lymph nodes (26.3%), cytokeratin-positive, disseminated tumor cells were detected. Cytokeratin-positive cells were found in at least one resected lymph node of each patient with ductal carcinoma of the pancreatic head (100%), whereas in patients with carcinoma of the papilla of Vater, no disseminated tumor cells were detected using the antibody against cytokeratin. Similarly, there was no detection of tumor cells (false-positive) in patients with chronic pancreatitis. In contrast, CA19-9 antigen was detectable in resected lymph nodes of each of the 25 carcinoma patients (pancreatic carcinoma and carcinoma of the papilla of Vater). Interestingly, 52 of 81 lymph nodes (64.2%) from the control group (chronic pancreatitis) were false-positive. CONCLUSION: Detection of disseminated tumor cells in lymph nodes using an antibody against cytokeratin is specific and suitable while use of an antibody against CA19-9 is not recommendable because of the high rate of false-positive results. The results may indicate that ductal pancreatic carcinoma generates early dissemination of tumor cells into lymph nodes. This may be one explanation for the poor outcome of this carcinoma compared with that of the carcinoma of the papilla of Vater (14 versus 48 months P < 0.05).

Adenocarcinoma↗

Distribution and characteristics of hematogenous disseminated tuberculosis within the abdomen on contrast-enhanced CT.

BACKGROUND: The incidence of abdominal tuberculous lymphadenopathy never appears low. In addition to infecting the abdominal lymph nodes through the digestive tract, the tuberculosis bacteria can also infect the abdominal lymph nodes and extra-nodal organs through hematogenous dissemination. This study investigated contrast-enhanced CT features and anatomic locations of hematogenous disseminated tuberculosis involving abdominal organs. METHODS: Thirteen patients with documented hematogenous disseminated tuberculosis involving abdominal organs were recruited. Contrast-enhanced CT scanning was carried out in the abdomen of all patients. CT images were retrospectively analyzed for the size, attenuation, enhancement patterns, and anatomic distribution of the foci in infected lymph node, liver, spleen, and kidney. RESULTS: Hematogenous disseminated tuberculosis dominantly affected lymph nodes in the hepatoduodenal ligament (84.6%), the portacaval space (84.6%), the root of the mesentery (84.6%), the peripancreatic region (84.6%), the periceliac region (76.9%), the hepatogastric ligament (69.2%), and the upper and lower paraaortic region (both were 69.2%). Out of the 13 cases studied, 12 (92.3%) had lymphadenopathy with peripheral enhancement accompanied by multilocular appearance; 10 (76.9%) had homogeneous hepatomegaly; 13 (100%) had inhomogeneous splenomegaly accompanied by scattered low-density lesions with peripheral enhancement; and 8 (61.5%) had low-density lesions in the kidney with peripheral enhancement. CONCLUSION: Anatomically, peritoneal and retroperitoneal lymph nodes are most susceptible to hematogenous disseminated tuberculosis. The hepatomegaly manifested to be homogeneous in most cases while the splenomegaly is of frequently inhomogeneous attenuation. All these characteristics are closely related to the infection routes and pathologic features of abdominal hematogenous disseminated tuberculosis.

Abdomen↗

Experimental study to evaluate the usefulness of S-1 in a model of peritoneal dissemination of gastric cancer.

BACKGROUND: Favorable results have been reported for the novel oral anticancer agent S-1 (TS-1) in clinical studies of advanced gastric cancer with peritoneal dissemination. In the present study we assessed its pharmacokinetics, inhibitory effects, and effect on survival time in an animal model. METHODS: A model of peritoneal dissemination was created by intraperitoneally implanting 4-week-old female BALBc nu/nu mice with the human gastric cancer cell line MKN-45 after transfection with a fluorescent protein-expressing vector. Pharmacokinetics were investigated by measuring intratumor, peritoneal lining, and blood concentrations after the administration of S-1 and fluorouracil (5-FU). The effect of S-1 on survival time was also assessed, by administration once daily to seven animals per group, starting on day 7 after implantation, and survival time was compared with that of an untreated control group. The inhibitory effect of S-1 on peritoneal dissemination was evaluated by killing mice at the start of administration, and 1 and 3 weeks after the start of administration, and examining them for the presence of peritoneal dissemination under a fluorescence stereomicroscope. RESULTS: Maintenance of high 5-FU concentrations in the intraperitoneal tumors was confirmed in the S-1 group, and survival time was prolonged without any decrease in oral food intake or body weight. CONCLUSION: Assessment in a model of peritoneal dissemination of gastric cancer showed that the novel oral anticancer agent S-1 was effective against peritoneal dissemination, and that it improved the survival rate.

Animals↗

Disseminated tumor cells in peripheral blood: a novel marker for therapy response in locally advanced rectal cancer patients undergoing preoperative chemoradiation.

PURPOSE: This study was designed to examine whether disseminated tumor cells in peripheral blood of locally advanced rectal cancer patients undergoing preoperative chemoradiation have the potential to serve as a marker for therapy response. Studies suggest that patients with advanced rectal cancer who respond to preoperative chemoradiation most likely benefit from this treatment. METHODS: From advanced rectal cancer patients undergoing preoperative chemoradiation, peripheral blood was obtained at defined times: before, during, and after chemoradiation and during surgery. Patients were divided into histopathologic responders (ypT0-T2) and nonresponders (ypT3-T4). Cytokeratin 20 and carcinoembryonic antigen reverse transcriptase-polymerase chain reaction were performed to detect disseminated tumor cells. A blood sample was deemed positive for disseminated tumor cells if both carcinoembryonic antigen and cytokeratin 20 were detected. RESULTS: The overall population (n = 26) showed a positivity rate of 32 percent for disseminated tumor cells before initiation of chemoradiation. Of the responders (n = 8), 63 percent were positive for disseminated tumor cells before chemoradiation, whereas only 18 percent of nonresponders (n = 18) were positive (P = 0.026). From initiation of chemoradiation to the end of surgery, a significant decrease was seen in tumor cell positivity in the blood of responders (P = 0.042). Moreover, the responders represented a trend toward a decrease in tumor cell positivity during chemoradiation (P = 0.079). In contrast, there were no noticeable alterations within the treatment course in nonresponders. CONCLUSIONS: This prospective proof of principle study demonstrates that locally advanced rectal cancer with preoperative chemoradiation shows different biologic behavior in terms of tumor cell dissemination in peripheral blood when therapy responders compared with nonresponders.

Adenocarcinoma↗

Cutaneous lesions of disseminated histoplasmosis in human immunodeficiency virus-infected patients.

Disseminated histoplasmosis is being diagnosed more frequently in persons infected with the human immunodeficiency virus and is often the initial manifestation of the acquired immunodeficiency syndrome (AIDS). Disease-related cutaneous features of HIV-associated disseminated histoplasmosis are defined as mucocutaneous lesions from which fungal organisms were either cultured or demonstrated histopathologically. We report four HIV-seropositive patients with disseminated histoplasmosis who had culture-positive skin or oral lesions of histoplasmosis and review the specific cutaneous manifestations of HIV-associated disseminated histoplasmosis. Including our patients, disease-related skin and/or mucosal lesions were present in 11% of patients (26% of 239) with HIV-associated disseminated histoplasmosis. The possibility of disseminated histoplasmosis should be considered in all HIV-infected persons and in persons with AIDS risk factors who have fever, weight loss, hepatosplenomegaly, and new cutaneous lesions. An early skin or mucosal biopsy specimen for crushed tissue preparation, histologic evaluation, and fungal culture is a simple, rapid diagnostic procedure.

Adult↗

Detection of disseminated tumor cells in mediastinoscopic lymph node biopsies and lymphadenectomy specimens of patients with NSCLC by quantitative RT-PCR.

OBJECTIVE: Detection of disseminated tumor cells in mediastinoscopic biopsies could improve staging and might be helpful concerning indications for neoadjuvant therapy regimens. This prospective study was performed to evaluate a simple and observer-independent polymerase chain reaction (PCR)-based method for the detection of disseminated tumor cells in regional lymph nodes. METHODS: Lymph nodes of 32 consecutive patients without neoadjuvant therapy were removed by systematic lymphadenectomy during resection of primary NSCLC. One hundred of these lymph nodes were cut into two equal halves which were examined using either routine histopathology or quantitative reverse transcriptase PCR (qRT-PCR). qRT-PCR amplification of cytokeratin 19 (CK19) transcripts was applied for the detection of tumor cell-specific RNA. We differentiated between illegitimate marker gene transcription and cancer-specific expression by using a cut-off value that was obtained from the analysis of 18 lymph nodes of patients with benign lung diseases. Subsequent to the evaluation of qRT-PCR, a pilot project with five additional patients was conducted to examine 19 mediastinoscopic biopsies, which were cut into two equal halves and proceeded as described above. RESULTS: Ninety-four (94%) lymph nodes were tumor-free by histopathology. qRT-PCR detected disseminated tumor cells in 26 (28%) of these lymph nodes. All of the remaining six lymph nodes that were judged by the pathologist to contain tumor cells exhibited CK19 transcripts. Twenty-three patients had a pN0 status. qRT-PCR detected disseminated tumor cells in 13 (56%) of these pN0 patients. The mediastinoscopic biopsies showed disseminated tumor cells in four (21%) out of 19 histopathologically tumor-free samples. CONCLUSIONS: CK19 qRT-PCR is a sensitive and specific tools for the detection of disseminated tumor cells in regional lymph nodes of patients with operable NSCLC. Further studies are required to asses if this molecular method might improve mediastinoscopic staging.

Aged↗

Enhancement of pleural dissemination and lymph node metastasis of intrathoracic lung cancer cells by vascular endothelial growth factors (VEGFs).

The expression of vascular endothelial growth factors (VEGFs) in tumors including lung cancer is considered to be associated with tumor development via capillary and lymph vessel neogenesis. Dissemination of the tumor cells to the pleura or regional lymph nodes is a critical poor prognostic factor for lung cancer patients. To investigate how VEGFs expressed in the intrathoracic infiltrating lung cancer cells participate in disease progression, we established stably VEGF-A-, VEGF-C-, VEGF-D-, VEGF-A and VEGF-C-, and VEGF-A and VEGF-D-expressing large cell lung cancer clones (TKB5/VEGF-A, TKB5/VEGF-C, TKB5/VEGF-D, TKB5/VEGF-A/C, and TKB5/VEGF-A/D), orthotopically inoculated these into the right thoracic cavity (i.t.) of nude mice, and evaluated the subsequent development of lung lesion, pleural effusion, pleural dissemination, and lymph node metastasis. While there were no significant differences either in culture or in subcutaneous tumor cell growth between the empty vector-transfected group (TKB5/empty) and each transfectant, the i.t. model demonstrated significantly different biological properties between the transfectants. TKB5/empty-inoculated mice frequently developed a large tumor on the pleura without pleural effusion, dissemination, or lymph node (LN) metastasis. In contrast, VEGF-A promoted a bloody pleural effusion (6/14), and VEGF-A and VEGF-D frequently generated pleural dissemination (11/14 and 9/11, respectively). Although both VEGF-C and VEGF-D generated LN metastasis (6/10 and 8/11, respectively), the locations of the metastasized LNs were quite different. TKB5/VEGF-C metastasized on the same side of axillary LNs as i.t. (right axillary LNs), whereas TKB5/VEGF-D metastasized to the mediastinal and left axillary and/or cervical LNs. Since the TKB5/VEGF-A/C or TKB5/VEGF-A/D co-transfectants revealed overlapping tumor progression patterns of VEGF-A and VEGF-C or VEGF-D, the metastatic LNs had abundant new capillaries and were larger than those of TKB5/VEGF-C or TKB5/VEGF-D-inoculated mice. Our results clearly demonstrate that VEGF-A secreted from intrathoracic lung cancer cells plays important roles in producing pleural effusion, dissemination, and capillary neogenesis, that VEGF-C is involved in LN metastasis, and VEGF-D in pleural dissemination and LN metastasis. It is most likely, however, that the mechanisms by which VEGF-C promotes LN metastasis are different from those of VEGF-D. The regulation of the expression of VEGFs in intrathoracic lung cancer cells might be a useful therapeutic approach to inhibiting tumor development and improving patient prognosis.

Animals↗

The risk of disseminated Bacille Calmette-Guerin (BCG) disease in HIV-infected children.

OBJECTIVES: Bacille Calmette-Guerin (BCG), a live attenuated Mycobacterium bovis vaccine, poses a risk to human immunodeficiency virus (HIV)-infected children; this risk has not been well quantified. We estimate the risk of disseminated BCG disease in HIV-infected children in a setting highly endemic for tuberculosis and HIV. DESIGN AND METHODS: We conducted a prospective hospital-based surveillance study in the Western Cape Province, South Africa. Clinical and laboratory-confirmed cases of disseminated BCG disease in children<1 year of age from January 2002 to December 2004 at a referral hospital were used as numerator data. Denominator data for calculations of disseminated BCG risk were obtained through estimating the total number of HIV-infected infants receiving BCG based on the known vaccination coverage in the study setting, combined with population data on the total number of children<1 year of age, the known HIV prevalence amongst women attending public antenatal care facilities and different scenarios (5-15%) for the rate of vertical HIV transmission. RESULTS: Nine cases of disseminated BCG disease were identified over the study period, seven of these were in HIV-infected infants. The estimated risk for HIV-infected infants to develop disseminated BCG disease, given a 95% BCG coverage and an HIV prevalence of 12.4-15.4% amongst women, were as follows for different scenarios of vertical HIV transmission: 329-417/100,000 vaccinees (assuming 5% vertical HIV transmission), 164-208/100,000 vaccinees (assuming 10% vertical HIV transmission) and 110-139/100,000 vaccinees (assuming 15% vertical HIV transmission). CONCLUSIONS: The risk of disseminated BCG disease is increased several hundred fold in HIV-infected infants compared to the documented risk in HIV-uninfected infants. Data on the protective effect of BCG in HIV-exposed and infected children is lacking. Population- and hospital-based surveillance is vitally important to more accurately estimate the safety and benefits of BCG in HIV-exposed and infected infants.

AIDS-Related Opportunistic Infections↗