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Leptomeningeal dissemination of malignant gliomas. Incidence, diagnosis and outcome.

To understand the clinicopathology features of leptomeningeal dissemination of malignant gliomas, a total of 157 consecutive patients treated between 1978 and 1989 were analysed. Twenty-two patients (14%) were judged to have dissemination. In 20 patients, the dissemination was diagnosed antemortem. Eleven patients had neurological deficits due to dissemination, whereas the other 9 without these had CT or myelographic evidence of dissemination. The peak incidence of dissemination was seen in the first and second decades of life. The mean age of 22 patients with dissemination was 31 years, significantly lower than that (44.5 years) of patients without dissemination. Fifteen patients developed dissemination within one year after diagnosis (early dissemination), 60% of them were less than 30 years of age. All patients with late dissemination (more than one year after diagnosis) underwent a second craniotomy for tumour removal before dissemination, while none of the 15 patients with early dissemination did. Survival after diagnosis in patients with dissemination was shorter, although statistically not significant, than that of patients without dissemination. Survival after dissemination was limited in all patients (mean 19 weeks, range 2-39 weeks). Immunohistochemical study revealed that the disseminated tumour expressed less glial fibrillary acidic protein than the primary tumour. Our results suggest that dissemination does not seem to result from extended survival of the patients, but may occur at any time in malignant gliomas. Some malignant gliomas, especially in younger patients, have a capability to acquire biological characteristics suitable for dissemination in the earlier stage of the disease.

Adolescent↗

Differential uptake of a smoking cessation programme disseminated to doctors and midwives in antenatal clinics.

AIMS: Two methods of dissemination (simple and intensive) were used to disseminate a smoking cessation programme to doctors and midwives working in antenatal clinics. This paper describes the differential uptake of the smoking cessation programme by doctors and midwives. It investigates whether the number of smoking cessation interventions used differ due to the type of dissemination. It also examines the frequency with which doctors and midwives provide smoking cessation interventions after dissemination. DESIGN: Clinics were randomized to the method of dissemination (simple or intensive). Pre-post test design was used to examine the relationship between dissemination method and professional status at baseline and follow-up. A baseline survey collected data on the use of smoking cessation intervention in the clinics prior to dissemination. A follow-up survey was conducted 18 months after the dissemination. SETTING: Twenty-three public hospital antenatal clinics in NSW. PARTICIPANTS: All clinical staff (midwives and doctors) working in the clinic during the 1-2-week survey period prior to dissemination and 18 months after the dissemination were asked to participate. The response rate was 63% (223) at baseline and 64% (182) at follow-up. Only 48% of midwives and doctors at follow-up were working in the original clinic. MEASURES: The proportion of clinicians who initially adopted the programme; the proportion of clinicians who had used one or more programme components in the last week); the number of types of smoking cessation intervention provided (maximum = 13), and the estimated proportion of clients offered smoking cessation intervention. FINDINGS: More midwives than doctors "ever used" the programme (76% vs. 25%) and continued to implement (58% vs. 22%) the programme 18 months after dissemination. Both midwives and doctors increased the number of types of smoking cessation intervention offered at follow-up compared to baseline (mean difference 2.8). Midwives provided more smoking cessation interventions than doctors at baseline (mean difference 0.9) and at follow-up (1.6), regardless of method used to disseminate the programme. Midwives' mean estimates of the proportion of clients offered interventions were greater than doctors' (midwives' 59% vs. doctors' 35%) at follow-up. CONCLUSION: The dissemination of a smoking cessation programme increased the level of smoking cessation interventions used by doctors and midwives. Doctors and midwives differ in their uptake of smoking cessation programmes. This information can be used to plan programme dissemination strategies in the future.

Analysis of Variance↗

Disseminated ependymomas of the central nervous system.

Ependymomas are rare central nervous system (CNS) neoplasms that occasionally disseminate along the neuraxis or to extraneural sites. Definitive criteria predictive of dissemination have yet to be determined. One hundred forty patients with CNS ependymoma (88 primary spinal and 52 primary intracranial tumors) were surgically treated by the senior author (F.J.E.) between 1986 and 1994. Sixteen patients (11.4%) demonstrated tumor dissemination. The disseminated group consisted of 11 (12.5%) of 88 primary spinal and five (9.6%) of 52 primary intracranial ependymomas. The authors retrospectively reviewed the patients with CNS ependymoma and have identified several characteristics associated with dissemination from the primary tumor site. The mean time from diagnosis to dissemination was 6.8 years. The patients with disseminated disease were younger (16.8 vs. 28.3 years old, p = 0.02), had fewer gross-total resections (29% vs. 68%, p = 0.015), and had tumors with higher proliferative indices (MIB-1 staining, 13.14% vs. 2.06%, p = 0.02). High-grade tumors had a mean proliferation index of 21%, versus 2.4% and 1.6% for myxopapillary and low-grade tumors, respectively (p = 0.0003). In contrast to previous studies, tumor histology was the most significant variable for time to dissemination as determined by multivariate analysis (p = 0.008). Myxopapillary and high-grade tumors were 3.6 and 5.6 times more likely to have a shorter time to dissemination than low-grade tumors. In addition, dissemination is associated with a worse prognosis. At follow-up review, 31% of patients with disseminated disease had died compared to 7% of patients without dissemination (p = 0.04). It is concluded that younger patients with subtotal resections, myxopapillary or high-grade histology, and tumors with high proliferative indices are at substantial risk for the development of disseminated disease during their clinical course.

Adolescent↗

Clinical features and outcome in disseminated mycobacterial diseases in AIDS patients in Taiwan.

OBJECTIVE: To describe and compare the clinical features and outcome of disseminated tuberculosis (TB) and Mycobacterium avium complex (MAC) disease in AIDS patients. DESIGN: Prospective cohort study. SETTING: A 1800-bed university teaching hospital, the largest centre for HIV/AIDS patients in Taiwan. METHODS: From July 1994 through June 1997, a standardized protocol was used to record the demographic and clinical features in all hospitalized HIV-infected patients, and to perform routine studies and invasive procedures for diagnosis of disseminated mycobacterial diseases. To compare the survival, control patients were selected from the HIV-infected patients hospitalized in the same hospital during the same study period, and had similar age, sex, CD4+ cell counts and antiretroviral therapy regimens. RESULTS: A total of 22 cases of disseminated TB and 15 cases of disseminated MAC were identified. Disseminated TB and MAC occurred in patients with similarly low CD4+ cell counts (median, 23 versus 5 x 10(6)/l; P = 0.08). The clinical features favouring disseminated TB included night sweats, peripheral lymphadenopathy, acid-fast bacilli in sputum smears, chest radiographic findings of hilar enlargement, and lack of prior AIDS-defining illnesses. Hepatosplenomegaly, elevated serum alkaline phosphatase (more than twice the upper limit of normal), elevated serum gamma-glutamyl transpeptidase (more than three times the upper limit of normal), and leukopenia favoured disseminated MAC. The patients with disseminated TB survived much longer than patients with disseminated MAC (mean survival, 96 versus 22 weeks, P = 0.008) but had a similar outcome to control patients (P = 0.60). CONCLUSION: Disseminated TB and MAC are distinguishable by clinical features in AIDS patients with similar immunocompromised states. Those features may facilitate diagnosis and selection of specific therapeutic regimens. Disseminated TB was not associated with a shortened survival period in AIDS patients when they completed anti-TB treatment. In contrast, disseminated DMAC was associated with shortened survival despite treatment with potent regimens. These results may emphasize the importance of prophylaxis for MAC in this population.

AIDS-Related Opportunistic Infections↗

ESID, dissemination, and community psychology: a case of partial implementation?

Dissemination, the second stage of Experimental Social Innovation and Dissemination (ESID) is a critical, if not defining, element of this social change model. This paper attempts to assess the extent to which community psychology has adopted and implemented ESID's dissemination focus in its training and publications. We identify four levels of commitment to dissemination: dissemination advocate, dissemination activist, dissemination researcher, and experimental dissemination researcher. Content analyses of textbooks, journal publications, and conference papers and a brief survey of doctoral training in the field were conducted. Findings suggest that the dissemination aspects of ESID have been modestly and partially implemented within the field. That is, although there is some evidence of a commitment to dissemination practice (advocate, activist), there is much less evidence of a commitment to dissemination research. The implications of these findings for the effectiveness of the ESID model and for training and practice in community psychology are discussed.

Diffusion of Innovation↗

Patterns of neuroaxis dissemination of gliomas: suggestion of a classification based on magnetic resonance imaging findings.

BACKGROUND: Local invasion is the hallmark of malignant glioma dissemination. Leptomeningeal dissemination, a serious complication of malignant gliomas, has been increasingly observed. To correlate the physiopathologic mechanisms and the magnetic resonance imaging patterns of neuroaxis dissemination, a classification of malignant glioma dissemination is proposed (Instituto de Neurologia de Curitiba Classification). METHODS: This classification includes the following patterns of dissemination: leptomeningeal (type I), nodular (type Ia), diffuse (type Ib); subependymal (type II); satellite (type IIIa, IIIb); and mixed (type IV), combination of 2 or more previous types. Of 138 patients with histologically confirmed gliomas treated between 2000 and 2004, 10 presented neuroaxis dissemination and were evaluated. RESULTS: The distribution of dissemination patterns was as follows: subependymal, 4 of 10; diffuse leptomeningeal, 1 of 10; nodular leptomeningeal, 1 of 10; and satellite, 4 of 10. Mean interval between primary tumor and dissemination was 4 months. The most frequent glioma dissemination risk factor was entering the ventricular system during surgery. CONCLUSIONS: Improvements in our diagnostic imaging capabilities have contributed to a better understanding of the patterns of malignant glioma dissemination. Using this information, we present a useful classification scheme, applicable to patients with neuroaxis dissemination, which will help standardize future discussions aimed at understanding these patterns of tumor spread.

Adolescent↗

Multivariate analysis of dissemination relapse of medulloblastoma and estimation of its time parameter for craniospinal irradiation.

PURPOSE: To examine in retrospect prognostic factors influencing meningeal dissemination relapse of medulloblastoma (MB) and to estimate time parameter gamma/alpha of the biologically effective dose for fractionated craniospinal irradiation (CSI). MATERIALS AND METHODS: Fifty-eight patients with MB who had been treated at our six hospitals from 1980 to 1990, were analyzed by the proportional hazards model consisting of radiation factors of both CSI and local irradiation (LI), sequential CSI time-lag, and eight non-radiation factors (gender, age, performance status, T-stage, dissemination score, extent of resection, and use of chemotherapy and immunotherapy). The gamma/alpha for CSI was estimated by the profile likelihood method using the maximum value of conditionally calculated time-incorporated biologically effective dose, tBEDmax, of the field treated with the least dose. RESULTS: Dissemination relapse was seen in 23 (40%) patients. Nineteen disseminations occurred within four years, and the cumulative dissemination-free rate was 64% at five years. The site of initial dissemination relapse was both cranial and spinal in 13 patients (57%). Dissemination relapse was accompanied with local failure in 43% (10/23) of patients, and four of them were seen later than four years. In the multivariate analysis, significant prognostic factors were dissemination score (p=0.0008) and total dose of CSI (p=0.018). The estimate of gamma/alpha for CSI was about 0.2 Gy/day in BED units. In another multivariate analysis including the best-fitted tBEDmax, significant prognostic factors were dissemination score and the tBEDmax of both CSI (p=0.021) and LI (p=0.024). CONCLUSION: This analysis indicated that the dissemination score, total dose of CSI, and tBEDmax of both CSI and LI were significantly prognostic for dissemination relapse of MB. The estimate of gamma/alpha for CSI was smaller than that derived from our previous analysis for LI. However, in order to estimate the time factor for CSI more precisely, a larger group of patients treated with concurrent CSI is needed.

Adolescent↗

Expression of MMP-7 and MT1-MMP in peritoneal dissemination of gastric cancer.

BACKGROUND/AIMS: In this study, we examined the expression of MMP-2, MMP-7, and MT1-MMP in peritoneal dissemination of gastric cancer, so as to clarify a possible role of these MMPs in developing peritoneal dissemination, using culture cells and an animal model with peritoneal dissemination. METHODOLOGY: Total RNA was extracted from tumor tissues of disseminated foci from 7 patients with gastric cancer and human gastric cancer cell lines of STSA, STKM-1, MKN-28, MKN-45, and KATOIII. Expressions of mRNA for MMP-2, MMP-7, and MT1-MMP were analyzed by reverse transcriptase-polymerase chain reaction. To examine relationships between the expression of these mRNAs and the ability to establish peritoneal dissemination, nude mice were injected into the intraperitoneal cavity with 106 cultured cells of those 5 gastric cancer cell lines. RESULTS: MMP-7 was expressed in 6 of 7 tissues (85.7%) and MT1-MMP in 2 of 7 tissues (28.6%), while MMP-2 was not detected in any of 7 tumor tissues. All 7 tumors had either MMP-7 or MT1-MMP. MMP-7 was recognized in 4 of 5 cells (80%) and MT1-MMP in 2 of 5 cells (40%), while MMP-2 was not found at all. All 5 cancer cells expressed at least one MMP mRNA. In the animal experiments, nude mice inoculated with STKM-1 or MKN-45 cells developed peritoneal dissemination, while those with other cell lines did not. MMP-7 was found both in STSA and MKN-28 (dissemination negative), and in STKM-1 and MKN-45 (dissemination positive). MT1-MMP mRNA was detected in one of two dissemination positive cell lines and in one of three dissemination negative ones. CONCLUSIONS: Our results suggested the importance of MMP-7 and MT1-MMP in the peritoneal metastases of gastric cancer, however, it has to be further dissected what role these MMPs might play in detaching of cancer cells from the gastric wall and establishing peritoneal disseminating foci.

Animals↗

Disseminated neuroblastoma in the nude rat. A xenograft model of human malignancy.

BACKGROUND: The overall survival of children with neuroblastoma remains less than 30% due to disease dissemination at the time of diagnosis. An animal model of neuroblastoma, with characteristics similar to those observed clinically in children, would be beneficial to investigations into the diverse biology of this tumor. The purpose of this study was (1) to develop a model of disseminated neuroblastoma in the nude rat by intracardiac injection of neuroblastoma cells derived from cell lines with different N-myc copy numbers; (2) to investigate the effect of age on tumor growth and dissemination; and (3) to assess progression of disease radiologically and correlate with autopsy findings. METHODS: Nude rats (n = 38), 5-13 weeks of age, underwent intracardiac injection of the human neuroblastoma cell lines IMR-32 with amplified N-myc oncogene and SKNSH with 1 N-myc copy. The animals were observed for at least six weeks for the development of tumor. Twelve rodents injected with IMR-32 cells underwent imaging studies including magnetic resonance imaging (MRI), skeletal radiographs, and indium-111(IN-111)-diethylenetriamine penta-acetic acid-D-Phe1-octreotide scintigraphy. Autopsies with standardized microscopic examinations were performed on all animals. RESULTS: Most of the nude rats (95%) developed neuroblastoma following intracardiac injection of neoplastic cells. Disseminated tumor was evident in 66% of animals. Anatomic sites of neuroblastoma growth were similar to those observed clinically in children, including adrenal glands, paraspinal ganglia, bone, bone marrow, and skin, but no tumor was identified in the liver. Disseminated disease occurred in more animals injected with IMR-32 (78% of animals) than with SKNSH cells (34% of animals) (P < 0.05). Tumor spread appeared to be age dependent; only rodents 5-8 weeks old at the time of injection developed disseminated disease when compared with animals 9 weeks of age or older (P < 0.0001). Radioreceptor scintigraphy demonstrated only pericardial tumor; MRI identified pericardial, adrenal gland, and subcutaneous neoplasms; only skeletal radiographs detected neuroblastoma in cortical bone. CONCLUSIONS: (1) Following intracardiac injection of human neuroblastoma cell lines into nude rats, a xenograft model of disseminated disease develops that closely parallels the malignant process in children. (2) Tumor dissemination is associated with the cell line that demonstrates N-myc amplification and with young age of the recipient at the time of injection. (3) Tumor growth and dissemination may be assessed radiologically. (4) This model of human malignancy may offer an opportunity to investigate the pathophysiologic mechanisms underlying tumor development and dissemination in advanced stage neuroblastoma.

Age Factors↗

Risk of dissemination with biopsy of colorectal liver metastases.

PURPOSE: Liver surgeons usually recommend against biopsy of colorectal liver metastases because of the risk of local dissemination. To date, only case reports describing this problem have been published. This study is an attempt to quantify the risk of biopsy-related dissemination. METHODS: A multicenter, retrospective review was undertaken of cases of colorectal liver metastases presenting for surgery that had undergone a preoperative biopsy. RESULTS: Two hundred thirty-one cases of colorectal liver metastases presenting for surgery were identified. Forty-three cases had undergone a preoperative biopsy (18.6 percent). Seven patients had evidence of dissemination related to the biopsy, giving a risk of dissemination of 16 percent (95 percent confidence interval, 7-30 percent). The risk of dissemination was not related to the type of biopsy. Within the follow-up period (median, 21 months), 3 of the 7 cases with evidence of dissemination and 11 of the 35 without dissemination were alive without disease. Twenty-five percent of the 36 cases without dissemination were resected, whereas 6 of the 7 cases with dissemination were resected. CONCLUSIONS: There is a significant risk of local dissemination with biopsy of colorectal liver metastases. In this series this was independent of the type of biopsy. There was no demonstrated effect on resectability or survival, but numbers were small, and the median follow-up was short.

Aged↗

Primary dissemination of high-grade gliomas in children: experiences from four studies of the Pediatric Oncology and Hematology Society of the German Language Group (GPOH).

PURPOSE: Clinical data on central nervous system (CNS) dissemination of high-grade gliomas (HGG) at initial presentation in children are rare. PATIENTS AND METHODS: We conducted a retrospective data analysis of all patients enrolled into four consecutive HGG protocols of the Pediatric Oncology and Hematology Society of the German Language Group (GPOH) to determine the incidence of primary CNS dissemination of HGG and to describe clinical characteristics and outcome of children with HGG who were diagnosed with CNS dissemination at initial presentation. 546 patients with newly diagnosed HGG (n=348) or diffuse intrinsic pontine gliomas (n=198) were enrolled in these four studies. Data concerning tumor dissemination are available from 324 patients. RESULTS: A total of 10 patients (3.1%) (anaplastic astrocytoma: n=3, glioblastoma multiforme: n=6, diffuse intrinsic pontine glioma: n=1) had primary tumor dissemination. Median age at diagnosis was 9.3 years (range: 0.3-21.3 years). The most frequent primary tumor sites were the cortex (n=4), followed by the ventricles (n=2), cerebellum (n=1), spinal cord (n=1), and pons (n=1). One patient had diffuse gliomatosis cerebri. Following surgery eight patients received local radiotherapy and eight additional chemotherapy. At a median follow-up of 10 months (range: 0.05-3 years) four patients are alive. None is disease-free. Median progression-free and overall survival was 0.8 years (95% CI 0.2-1.4) and 1.5 years (95% CI 0.67-2.29) for patients with primary tumor dissemination, respectively, with no statistically significant differences between the group with and the group without primary tumor dissemination. CONCLUSIONS: Initial diagnostic evaluation should include complete CNS imaging as well as cerebrospinal fluid examination in all patients with HGG. As prognosis of children with HGG and primary CNS dissemination was not inferior to patients without dissemination in our population, these patients should be treated in the same way as patients without primary CNS dissemination.

Adolescent↗

Symptomatic spinal dissemination of malignant astrocytoma.

OBJECT: Symptomatic spinal dissemination of malignant astrocytoma is rarely found except at autopsy. This study evaluated the clinical incidence and characteristics of spinal dissemination and the effect on outcome. PATIENTS AND METHODS: Patients treated for primary malignant astrocytoma, including 33 with anaplastic astrocytoma and 35 with glioblastoma, at our department between 1997 and 1999 were followed up until April 30, 2001. Head magnetic resonance (MR) imaging of all patients was obtained every 2-3 months. Signs and symptoms of leptomeningeal spread were checked at monthly outpatient examinations. Spinal MR imaging was performed if any symptoms indicating spinal dissemination were found. RESULTS: Median survival times of patients with anaplastic astrocytoma and glioblastoma were 40.5 and 16.0 months, respectively. Seventeen patients (25%) developed intracranial dissemination and 15 of these died. Six patients (8.8%), one with anaplastic astrocytoma and five with glioblastoma, developed spinal dissemination. All patients with spinal dissemination also had intracranial dissemination. Five of the six patients died, despite systemic radiochemotherapy in four patients. All patients died of extensive whole brain and spinal dissemination or nodular mass enlargement at the upper cervical cord, not of local massive tumor progression. CONCLUSIONS: Symptomatic spinal dissemination of malignant astrocytoma is not so rare, and is the cause of death. The relatively high incidence of symptomatic leptomeningeal dissemination must be considered in the treatment of malignant astrocytomas.

Adolescent↗

Coccidioidomycosis in potentially compromised hosts: the effect of immunosuppressive therapy in dissemination.

Charts of 126 patients with coccidioidomycosis were reviewed. Sixteen of these were patients who had malignancies, uremia, or a collagen-vascular disease and/or had received recent immunosuppressive drug therapy. The rate of disseminated infection was 50% in this group. (The dissemination rate was 14% in 110 control patients.) No case of dissemination occurred in patients who only had the above underlying diseases; all cases of dissemination were among those who had received immunosuppressive therapy. The dissemination rate in control patients was higher for patients age 40 or over than for younger patients. The dissemination rate showed no age-related difference, however, in patients treated with immunosuppressive drugs. The dissemination rate was similar in control patients of both sexes and uniformly higher for both immunosuppressively treated males and females. The dissemination rate did not appear to be influenced by the number of circulating lymphocytes if the patient had received immunosuppressive drugs. Patients with disseminated disease who had received immunosuppressive drugs were capable of producing a serological response to the coccidoiidal organism in high titer but none had positive skin test reactivity. Disseminated coccidioidomycosis is not uniformly fatal in the immunosuppressed host: half of our patients are alive an average of 33 months after diagnosis.

Adolescent↗

Integrated PET/CT and the dry pleural dissemination of peripheral adenocarcinoma of the lung: diagnostic implications.

OBJECTIVE: The aim of this study was to describe retrospectively the CT findings of dry pleural dissemination of peripheral lung adenocarcinoma, and to compare the mutual roles of PET and CT components of integrated PET/CT in the diagnosis of the disease. METHODS: The authors analyzed retrospectively the CT findings of pathologically proved dry pleural dissemination in 8 of 172 patients with peripheral adenocarcinoma of the lung. Subsequently, one radiologist and one nuclear medicine physician (unaware of the CT and pathologic results) evaluated together in a random order the integrated PET/CT of 172 adenocarcinoma patients (8 with dry pleural dissemination and 164 without). They recorded the presence of pleural dissemination using PET images only and using both PET and CT images. The diagnostic accuracies with respect to the presence of pleural dissemination were evaluated. RESULTS: The CT findings of dry pleural dissemination were pleural small nodules (n=8, 100%) (>or=6 in number in all patients; 198/204 nodules were <5 mm in diameter and 6/204 were 5-10 mm) and uneven (n=4, 50%) or band-like (n=3, 38%) fissural thickening. By PET only, the sensitivity, specificity, and accuracy of dry pleural dissemination were 25% (2/8), 90% (147/164), and 87% (149/172), respectively; by PET plus CT these were 100% (8/8), 100% (164/164), and 100% (172/172), respectively. CONCLUSIONS: The CT findings of dry pleural dissemination are multiple small pleural nodules and uneven pleural thickening. Dry pleural dissemination should be diagnosed using CT findings at integrated PET/CT because lesions causing pleural dissemination without pleural effusion are usually beyond PET resolution.

Adenocarcinoma↗

Information dissemination and use: critical components in occupational safety and health.

BACKGROUND: Information dissemination is a mandated, but understudied, requirement of occupational and environmental health laws and voluntary initiatives. Research is needed on the factors that enhance and limit the development, transfer, and use of occupational safety and health information (OSH). Contemporary changes in the workforce, workplaces, and the nature of work will require new emphasis on the dissemination of information to foster prevention. METHODS: Legislative and regulatory requirements and voluntary initiatives for dissemination of OSH information were identified and assessed. Literature on information dissemination was reviewed to identify important issues and useful approaches. RESULTS: More than 20 sections of laws and regulations were identified that mandated dissemination of occupational and environmental safety and health information. A four-stage approach for tracking dissemination and considering the flow of information was delineated. Special areas of dissemination were identified: the information needs of the changing workforce, new and young workers; small businesses; and workers with difficulty in understanding or reading English. CONCLUSIONS: We offer a framework for dissemination of OSH information and underscore the need to focus on the extent to which decision-makers and others receive and use such information. More solid data are also needed on current investments in disseminating, diffusing and applying OSH information and on the utility of that information. Am. J. Ind. Med. 44:515-531, 2003. Published 2003 Wiley-Liss, Inc.

Humans↗

Dissemination of heart health promotion in the Ontario Public Health System: 1989-1999.

This paper reports the results of an analysis of the dissemination of community-based heart health promotion strategies. The research draws on diffusion and socio-ecological theories to study the first 10 years of heart health promotion in the public health system in Ontario, Canada. Using case description and interpretive analysis, the study describes developments in five stages of dissemination, and examines the interplay of factors operating in the internal organizational setting and the external environment in order to explain these developments. Findings demonstrate that dissemination of health promotion is a long-term, iterative process involving multiple stages. Dissemination is influenced by a complex interplay of factors operating within the public health system (especially traditional public health practice and champions) and factors in the environment in which the public health system operates (especially research, practice information and health policies). Implications are that policy makers should take a long-term view of dissemination, identify intermediate and long-term goals consistent with dissemination stages, and capitalize on internal and external forces supporting dissemination goals. Similar case-study research in other public health systems and time periods, and in more advanced stages of dissemination, will add further insight into the dissemination process.

Health Promotion↗

An unusual case of an ulcerative colitis flare resulting in disseminated intravascular coagulopathy and a bladder hematoma: a case report.

BACKGROUND: Disorders of coagulation have long been associated with inflammatory bowel disease. Children, as well as adults, with both active and inactive ulcerative colitis have been found to have abnormal coagulation and fibrinolysis. Disseminated intravascular coagulation arises from an overwhelming of the haemostatic regulatory mechanisms leading to an excessive generation of thrombin and a failure of the normal inhibitory pathways to prevent systemic effects of this enzyme. Ulcerative colitis has been associated with disseminated intravascular coagulation in conjunction with septicemia, toxic megacolon and surgery. CASE PRESENTATION: A fourteen-year-old boy with a history of poorly controlled ulcerative colitis presented with nonbilious emesis, hematochezia, and hematuria. Laboratory workup revealed disseminated intravascular coagulation. He was placed on triple antibiotics therapy. An infectious workup came back negative. A computerized tomography (CT) scan of the abdomen revealed a marked thickening and irregularity of the bladder wall as well as wall thickening of the rectosigmoid, ascending, transverse, and descending colon. Patient's clinical status remained stable despite a worsening of laboratory values associated with disseminated intravascular coagulation. Patient was begun on high dose intravenous steroids with improvement of the disseminated intravascular coagulation laboratory values within 12 hours and resolution of disseminated intravascular coagulopathy within 4 days. A thorough infectious workup revealed no other causes to his disseminated intravascular coagulation. CONCLUSIONS: The spectrum of hypercoagulable states associated with ulcerative colitis varies from mild to severe. Although disseminated intravascular coagulation associated with ulcerative colitis is usually related to septicemia, toxic megacolon or surgery, we present a case of an ulcerative colitis flare resulting in disseminated intravascular coagulation and a bladder hematoma.

Adolescent↗

Dissemination and tissue invasiveness in murine acute leukemia associated with acquisition of p53 mutation and loss of wild-type p53.

Approximately 60% of mice treated with split-dose radiation develop leukemias that disseminate widely through the body, whereas 40% of the treated mice incur leukemias that are contained entirely within the thymus. We studied the status of p53 in non-cultured samples of thymic leukemias and in cell lines established from these leukemias. In those mice with disseminated disease, primary samples were also obtained from visceral leukemic organs, and cell lines were established from these leukemic organs for further study. Using single-strand conformation polymorphism (SSCP), nucleic acid sequencing, and immunochemical analysis, we found that mutation of both p53 alleles occurred in leukemic cell lines developed from nine of 10 disseminated leukemias; mutation of one p53 allele with the other remaining wild-type occurred in one disseminated leukemia. A p53 mutation unique for each mouse was found in all cell lines established from the different leukemic organs of each mouse. The same mutation was also found in the non-cultured leukemic tissues of each mouse, indicating that the mutations originated in vivo and were clonal. Seven of seven non-disseminating thymomas possessed wild-type p53 only. Hence, in vivo dissemination and tissue invasiveness were associated with the loss of wild-type p53 by mutation of both alleles or by mutation and loss of heterozygosity, as revealed by studies of cell lines established from them. The selective in vivo dissemination of leukemia cells possessing p53 mutations had a parallel in vitro. Leukemia cell lines from mice harboring disseminating leukemia were established more readily (success rate greater than 80%) than lines from mice harboring thymic nondisseminating leukemia (success rate less than 10%). Additionally, while mice with disseminating leukemia harbored a mixture of wild-type and mutant p53-encoding thymoma cells, only cell lines possessing mutant p53 became established in culture. Mutations found in thymoma cell lines were always detectable by SSCP and sequencing of DNA extracted from non-cultured thymoma tissue. However, in non-cultured leukemic tissue of visceral organs, the clonal p53 mutations found in cell lines established from them were often not detectable by SSCP or sequencing but were detectable by immunochemical analysis or polymerase chain reaction amplification. This indicates an unexpected degree of masking of mutant genes by wild-type genes present in the leukemic tissue. Masking was evident even in leukemic organs that were grossly larger than normal organs. Hence, routine screening of leukemic tissue by SSCP and sequencing may result in a highly significant underestimation of the incidence of p53 mutations.(ABSTRACT TRUNCATED AT 400 WORDS)

Alleles↗