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Results for “Dissemination”

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At least 181 records · Page 10Linked to original sources

PubMed2004

Detection of disseminated tumor cells in peripheral blood of patients with breast cancer: correlation to nodal status and occurrence of metastases.

OBJECTIVE: Soon after breast cancer becomes invasive, it sheds cancer cells into the blood stream or the cancer cells are spread via lymphatic vessels. The early and unambiguous detection of these disseminated tumor cells (DTC) is of importance for the evaluation of the tumor process and for monitoring therapy response. The detection of disseminated tumor cells by immunocytochemistry (ICC) without previously performing tumor cell enrichment is time consuming and may miss a considerable part of these cells. Therefore, we have applied a negative immunomagnetic enrichment of disseminated tumor cells from the peripheral blood of patients with breast cancer by the depletion of CD45(+) leukocytes using automated magnetic activated cell separation (autoMACS). METHODS: One hundred twenty-five blood samples from 83 breast cancer patients were investigated for occurrence of disseminated tumor cells by autoMACS technique and immunocytochemical cytokeratin staining. Frequency of disseminated tumor cells was analyzed statistically for correlation to clinical data. RESULTS: Thirty-three of the 125 blood samples (26%) originating from 29 of 83 breast cancer patients (35%) carried cytokeratin positive (CK(+)) tumor cells. The occurrence of CK(+) tumor cells correlated significantly with the nodal status (P = 0.009) and with the occurrence of metastases at the time of primary tumor resection (P = 0.003). CONCLUSIONS: The finding that occurrence DTC detected in peripheral blood of breast cancer patients correlated with nodal stage and metastases is described for the first time. It suggests that disseminated tumor cells identified in peripheral blood by autoMACS are associated with tumor characteristics of breast cancer.

Adult↗

PubMedDate not supplied

Ventriculolumber perfusion of 3-[(4-amino-2-methyl-5-pyrimidinyl)-methyl]-1-(2-chloroethyl-1-nitrosou rea hydrochloride for subarachnoid dissemination of gliomas.

The toxicity and therapeutic effect of the ventriculolumber perfusion of 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl-1-1(2-chloroethyl)-1-nitros our ea hydrochloride (ACNU) against subarachnoid dissemination of gliomas were studied. Twenty-one patients (6 patients with anaplastic glioma, 7 with glioblastoma and 8 with medulloblastoma or PNET) received ventriculolumber perfusion of ACNU when they were diagnosed as having subarachnoid dissemination. The course of perfusion and cumulative dose of ACNU was 10 times and 95 mg on average, respectively. Most of the patients received systemic chemotherapy in combination with perfusion therapy and some patients with radiotherapy. Response rate was 17% and median survival time after the diagnosis of dissemination was 12 months for anaplastic gliomas, 29% and 12 months for glioblastoma, and 88% and over 25 months for medulloblastoma and PNET. The ventriculolumber perfusion of ACNU was performed for prophylactic purpose in 7 patients with high risk at the early postoperative period in combination with conventional adjuvant therapy. The course of perfusion and cumulative dose of ACNU was 2.3 times and 21 mg on average, respectively. One patient developed subarachnoid dissemination and died 22 months after surgery. Other 6 patients survived without dissemination on median over 29 months after surgery. Side effects encountered were headache in 4 patients, nausea and vomiting in 5, a convulsion in 2, right facial weakness in 1, fecal incontinence in 3 and meningitis in 2. They were all temporary except for facial weakness occurred in one patient. These data suggest that the ventriculolumber perfusion of ACNU is a safe and useful in the treatment and prophylaxis against the subarachnoid dissemination of gliomas.

Adolescent↗

PubMed1994

Serum D-arabinitol measured by automated quantitative enzymatic assay for detection and therapeutic monitoring of experimental disseminated candidiasis: correlation with tissue concentrations of Candida albicans.

In order to further understand serum D-arabinitol (DA) as a marker for the diagnosis of disseminated candidiasis and for monitoring response to antifungal therapy, we studied the serum levels of this Candida carbohydrate metabolite by rapid automated enzymatic assay in rabbits with experimental disseminated candidiasis. The enzymatic reaction steps were performed on a standard automated clinical chemistry analyser. As a correction for renal impairment, data were expressed as serum D-arabinitol/creatinine ratio (DA/Cr). Serum creatinine concentrations were determined from the same sample with the same instrument, thereby allowing rapid determination of the DA/Cr within one laboratory. The DA/Cr was determined in 321 samples from 132 rabbits. The mean serum DA/Cr in 31 normal non-infected rabbits was 1.51 +/- 0.2 microM mg-1 dl-1. Among 84 rabbits with disseminated candidiasis and pre-terminal samples, there was a direct correlation between DA/Cr and tissue concentration of Candida albicans (r = 0.80; P < 0.001). A threshold of elevated DA/Cr (> or = 3.0 microM mg-1 dl-1) was evident in rabbits with a tissue concentration of C. albicans > or = 3 x 10(4) colony forming units (CFU) g-1. Elevated DA/Cr was detected in 48 (89%) of 54 rabbits at a C. albicans tissue concentration of > or = 3 x 10(4) CFU g-1 vs. one (3%) of 30 rabbits with < 3 x 10(4) CFU g-1 (P < 0.0001). Among all 101 rabbits with disseminated candidiasis, an elevated DA/Cr was detected at any point during infection in 60 (92%) of 65 rabbits having a C. albicans tissue concentration > or = 3 x 10(4) CFU g-1 vs. 13 (36%) of 36 rabbits with < 3 x 10(4) CFU g-1 (P < 0.0001). The relationship between the tissue response to antifungal therapy and change in DA/Cr was then further analysed. Ten (91%) of 11 rabbits with a tissue-proven response to antifungal therapy (defined as > or = 10(2)-fold reduction of CFU g-1 in comparison to untreated controls) had a > 50% reduction in elevated DA/Cr levels. By comparison, 10 (83%) of 12 treated rabbits with no response to therapy had persistently elevated DA/Cr levels (P < 0.001). These findings provide an experimental basis for understanding the patterns of expression of serum DA in disseminated candidiasis and further indicate that serial DA/Cr measurements may be useful for diagnosis and therapeutic monitoring of disseminated candidiasis.

Animals↗

PubMed2005

The natural history of a novel, systemic, disseminated model of syngeneic mouse B-cell lymphoma.

Lymphomas and leukemias, neoplasms of hematopoetic lineage, pose unique challenges that require novel treatment paradigms. The inter-relationship between the immune system and the neoplastic lesion in these diseases dictates that, to evaluate novel therapies, models are needed that mimic human disease in an immunocompetent host. In the present study, we describe a disseminated, syngeneic model of B-cell lymphoma in the Balb/c mouse based upon the A20 cell line. This model mimics aspects of diffuse large B-cell lymphomas in humans, and recapitulates para-spinous tumor growth, bone destruction and nerve root compression, which may complicate disseminated disease. Furthermore, this tumor expresses a key marker of interest, CD40, which is a candidate for tumor-specific vector targeting via current modalities. The present study therefore describes a high-fidelity model of disseminated lymphoma with implications for novel targeted therapeutics. Lymphomas and leukemias, neoplasms of hematopoetic lineage, pose unique challenges that require novel treatment paradigms. The inter-relationship between the immune system and the neoplastic lesion in these diseases dictates that, to evaluate novel therapies, models are needed that mimic human disease in an immunocompetent host. In the present study, we describe a disseminated, syngeneic model of B-cell lymphoma in the Balb/c mouse based upon the A20 cell line. This model mimics aspects of diffuse large B-cell lymphomas in humans, and recapitulates para-spinous tumor growth, bone destruction and nerve root compression, which may complicate disseminated disease. Furthermore, this tumor expresses a key marker of interest, CD40, which is a candidate for tumor-specific vector targeting via current modalities. The present study therefore describes a high-fidelity model of disseminated lymphoma with implications for novel targeted therapeutics.

Animals↗

PubMedDate not supplied

Experimental basis for use of fluconazole for preventive or early treatment of disseminated candidiasis in granulocytopenic hosts.

To determine the potential for the use of fluconazole for prevention and treatment of disseminated candidiasis in granulocytopenic patients, we investigated its activity and pharmacokinetics in models of acute, subacute, and chronic forms of disseminated candidiasis in persistently granulocytopenic rabbits. Fluconazole was administered for systemic prophylaxis, early treatment, and delayed treatment. Single-dose and steady-state plasma pharmacokinetics, tissue penetration, and dose-response studies of the investigational compound were studied in subacutely infected granulocytopenic rabbits. Fluconazole was more effective when used for systemic prophylaxis or early treatment of disseminated candidiasis than for delayed treatment. Fluconazole was as effective as amphotericin B plus flucytosine in preventive and early treatment of disseminated candidiasis but was significantly less effective than amphotericin plus flucytosine in the treatment of chronic candidiasis. Dose-response studies demonstrated that the antifungal effect of fluconazole was dose- and time-dependent. Studies of the pharmacokinetics of fluconazole in rabbits demonstrated a long half-life in plasma and a large volume of distribution, properties that correspond to the attainment of high levels of penetration into tissues at multiple organ sites. We conclude that fluconazole is effective for prevention and early treatment of disseminated candidiasis in persistently granulocytopenic rabbits and that the evaluation of its use in preventive or early treatment of disseminated candidiasis in carefully designed clinical trials is warranted.

Acute Disease↗

PubMed1991

Natural history of disseminated Mycobacterium avium complex infection in AIDS.

This study sought to better characterize the natural history of AIDS-associated disseminated Mycobacterium avium complex (MAC) infection. Towards that end two retrospective studies were done: a case-control survival study and a MAC respiratory colonization study. Among 137 consecutive patients who had a sterile body site cultured for mycobacteria within 3 months of their first AIDS-defining episode of Pneumocystis carinii pneumonia, median survival was significantly shorter in those with disseminated MAC infection (107 days; 95% confidence interval [CI] 55-179) than those with negative cultures (275 days; 95% CI 230-318; P less than .01), even after controlling for age, absolute lymphocyte count, and hemoglobin concentration. Among 34 patients with AIDS and respiratory MAC colonization, 22 later developed disseminated infection (65% predictive value for subsequent MAC dissemination). Disseminated MAC infection was associated with significantly shorter survival for patients with AIDS, and the presence of MAC in respiratory specimens has substantial predictive value for subsequent disseminated infection.

Acquired Immunodeficiency Syndrome↗

PubMed2000

Detection of hematogenic tumor cell dissemination in patients undergoing resection of liver metastases of colorectal cancer.

OBJECTIVE: To determine the extent of pre- and intraoperative hematogenic tumor cell dissemination in patients undergoing liver resection for metastatic colorectal cancer. SUMMARY BACKGROUND DATA: For patients with hepatic metastases of colorectal cancer, liver resection is the only potentially curative therapy. However, 38% to 53% of patients develop extrahepatic tumor recurrence, probably caused by tumor cells disseminated before or during surgery not detected by current staging systems. METHODS: Blood samples harvested before, during, and after surgery from 41 patients and bone marrow samples from 30 patients undergoing resection of liver metastases of colorectal cancer were analyzed for disseminated tumor cells using cytokeratin 20 reverse transcriptase-polymerase chain reaction. RESULTS: Tumor cells were detected in the blood samples of 26 of the 41 patients (63.4%) and in the bone marrow samples of 8 of the 30 patients (26.7%). Tumor cells were detected significantly more often during surgery than before or after surgery. Intraoperative tumor cell dissemination was detected in 41.7% of patients undergoing resection of two or more liver segments but only 14.3% of patients undergoing resection of one liver segment. Compared with resection of primary colorectal cancer, major liver resection carries an increased risk for intraoperative tumor cell dissemination. CONCLUSIONS: Detection of disseminated tumor cells in patients undergoing liver resection for metastases of colorectal cancer using cytokeratin 20 reverse transcriptase-polymerase chain reaction might help to identify patients at high risk for tumor recurrence who may benefit from adjuvant therapy. Major liver resection of metastases leads to frequent intraoperative tumor cell shedding, possibly preventable by alternative surgical strategies.

Adult↗

PubMed2004

Disseminated intravascular coagulation and coagulation disorders.

PURPOSE OF REVIEW: An update on recent developments in diagnosis and treatment of disseminated intravascular coagulation. RECENT FINDINGS: Disseminated intravascular coagulation is defined as a typical disease condition with laboratory findings indicating massive coagulation activation and reduction in procoagulant capacity. Clinical syndromes associated with the condition are consumption coagulopathy, sepsis-induced purpura fulminans, and viral hemorrhagic fevers. Consumption coagulopathy is observed in patients with sepsis, aortic aneurysms, acute promyelocytic leukemia, and other disseminated malignancies. Sepsis-induced purpura fulminans is characterized by microvascular occlusion causing hemorrhagic necrosis of the skin and organ failure. Viral hemorrhagic fevers result in massively increased tissue factor production in monocytes and macrophages, inducing microvascular thrombosis and consumption of platelets and coagulation factors. Current scoring systems do not distinguish between patients with asymptomatic disseminated intravascular coagulation, consumption coagulopathy and thrombotic syndromes. Patients with sepsis may be identified by activated partial thromboplastin time waveform analysis performed as part of routine coagulation testing. Drotrecogin alpha (activated) reduces mortality in patients with severe sepsis with and without disseminated intravascular coagulation and has been used in patients with sepsis-induced purpura fulminans. Tifacogin does not reduce mortality in severe sepsis associated with impaired coagulation. Patients with heterozygous factor V Leiden mutation and severe sepsis showed a lower 28-day mortality than patients without this mutation, supporting the assumption that an enhanced level of coagulation activation may be beneficial in patients with severe sepsis. SUMMARY: Whereas antithrombin and tifacogin failed to improve clinical outcome in severe sepsis, drotrecogin alpha (activated) increased the chances of survival of patients with severe sepsis with and without disseminated intravascular coagulation.

Journal Article↗

PubMed2006

Disseminated nontuberculous mycobacterial infections in sickle cell anemia patients.

Nontuberculous mycobacteria (NTM) are ubiquitous in nature and have been implicated in skin/soft-tissue, pulmonary, middle ear, bone, and surgical/traumatic wound infections. Disseminated disease occurs infrequently and almost exclusively in the immunocompromised. We describe the first 2 reported cases of disseminated Mycobacterium fortuitum infection in teenagers with sickle hemoglobinopathy. Both had central venous catheters (CVCs), frequent admissions for vaso-occlusive painful episode and received hydroxyurea. Diagnosis was confirmed by multiple positive blood cultures and pulmonary dissemination occurred in both. Both had successful treatment after CVC removal and combination drug therapy. Positive cultures persisted in 1 patient due to drug resistance emphasizing the need for accurate susceptibility data. NTM infection should be added to the list of pathogens in sickle cell patients with CVCs and fever. Investigation for disseminated disease should be undertaken based on clinical signs and symptoms. Although some routine blood culture systems can identify NTM, specific mycobacterial blood culture is optimal. Removal of involved CVCs is essential and treatment of NTM must be guided by susceptibilities. As dissemination almost always occurs in those with impaired cellular immunity, human immunodeficiency virus testing should be performed. Hydroxyurea may be a risk factor for dissemination and needs further evaluation.

Acetamides↗

PubMed2005

Detection of hematogenous tumor cell dissemination predicts tumor relapse in patients undergoing surgical resection of colorectal liver metastases.

OBJECTIVE: To examine the prognostic significance of disseminated tumor cells in blood and bone marrow of patients undergoing surgical resection of colorectal liver metastases. SUMMARY BACKGROUND DATA: Despite curative hepatic resection of colorectal liver metastases, a high percentage of patients develop tumor recurrence. These recurrences probably originate from disseminated tumor cells released into the circulation before or during surgery. METHODS: Thirty-seven patients with potentially curative (R0) resection of colorectal liver metastases were prospectively enrolled into the study. Preoperative bone marrow samples and preoperative, intraoperative, and postoperative blood samples were examined for disseminated tumor cells by CK20 RT-PCR. RESULTS: Tumor cells were detected in preoperative blood samples in 11 of 37 (30%) patients, in intraoperative blood samples in 17 of 37 (46%) patients, and in postoperative blood samples in 8 of 37 (22%) patients. Four of 25 (16%) patients tested positive for disseminated tumor cells in bone marrow samples. Median follow-up time for all patients was 38 months (range, 10-63 months). Multivariate analysis confirmed tumor cell detection in intraoperative blood (P = 0.009) and in bone marrow samples (P = 0.013) to be independent prognostic factors of tumor relapse. CONCLUSIONS: This is the first study demonstrating that detection of hematogenous tumor cell dissemination during hepatic resection of colorectal cancer metastases predicts tumor relapse. Detection of disseminated tumor cells may help to individualize adjuvant therapy for patients with colorectal liver metastases and to develop surgical strategies to prevent intraoperative hematogenous tumor cell shedding.

Aged↗

PubMed1976

Dinitrochlorobenzene responsivity in disseminated coccidioidomycosis: an inverse correlation with complement-fixing antibody titers.

The immunologic status of 25 patients with disseminated coccidiodomycosis was evaluated by serum anticoccidioidin complement-fixing antibody levels, coccidiodin skin tests, and dinitrochlorobenzene (DNCB) sensitization. In the 10 patients who had disseminated disease and a complement-fixing titer of 1:32 or less, responses to DNCB were similar to those of 20 controls. In the 15 patients with disseminated disease and a complement-fixing titer of 1:64 or more, responses to DNCB were statistically significantly diminished compared to controls (p = 0.002). Since the complement-fixing titer is associated with extent of dissemination, these results signify a relationship between diminished DNCB responses and extensive dissemination. Of the several hypotheses which might explain this relationship, we find the most attractive is that of a nonspecific deficiency of cell-mediated immunity developing secondarily to extensive disseminated disease.

Adolescent↗

PubMed2005

Sharing empirical knowledge to improve breastfeeding promotion and support: description of a research dissemination project.

BACKGROUND: Effective transfer of research findings to health care settings is a shared priority among researchers, clinicians, and decision makers. A multidisciplinary, multi-method investigation conducted in 2001 that explored breastfeeding practices and support within a large immigrant community in Montreal, Quebec, Canada, bore numerous implications for practice. Peer-reviewed funding was subsequently granted to support dissemination of these findings to relevant stakeholders. METHOD: Key steps in implementing this research dissemination project included (1) identifying and attracting target audiences from hospitals, community health settings, and government agencies; (2) tailoring tools for communication of research findings to the various needs of audiences; (3) designing interactive workshops to facilitate knowledge uptake; and (4) integrating the project outcomes within a government-sponsored regional breastfeeding committee for longer-term impact. FINDINGS: Despite organizational challenges, more than 90 health care providers, decision makers, and breastfeeding support volunteers participated in the project workshops. Through feedback loops, the dissemination activities contributed new layers of understanding to the original research findings. The activities also engaged audience members to identify more effective breastfeeding support interventions and led to the adoption of breastfeeding support priorities shared by hospital, community, and government stakeholders. CONCLUSION: This dissemination project provided unique opportunities for researchers and stakeholders to share in the interpretation of research findings and to strategically plan for future interventions to promote and support breastfeeding within ethnically diverse communities. Further research dissemination work should continue to be theoretically grounded, include systematic, long-term assessment of dissemination outcomes, and be adequately financed throughout.

Breast Feeding↗

PubMed2006

Transvascular dissemination of Porphyromonas gingivalis from a sequestered site is dependent upon activation of the kallikrein/kinin pathway.

BACKGROUND AND OBJECTIVE: Epidemiological evidence implicates a connection between human periodontitis and systemic diseases. One possible mechanism involves the direct dissemination of periodontopathogens to the target organs through the circulation. The aim of this work was to define the mechanism used by Porphyromonas gingivalis for dissemination from a sequestered infection site. MATERIAL AND METHODS: BALB/c mice were subcutaneously infected with P. gingivalis via use of a mouse chamber model. Tissue fluids from various sites were collected and cultured to determine the presence of P. gingivalis. Evans Blue dye was used to measure the dissemination ability of P. gingivalis. Kinin-associated molecules were introduced into mice, and their effects on bacterial dissemination and mouse pathology were monitored. RESULTS: P. gingivalis strain A7436 caused remote lesions and septicemia with severe cachexia, resulting in animal death. Intrachamber challenge with A7436 resulted in vascular permeability enhancement (VPE), as measured by the systemic infiltration of Evans Blue dye into chamber fluids. VPE was blocked by kininase and kinin receptor antagonist and enhanced by exogenous bradykinin and kininase inhibitor. Live bacteria were recovered from the subcutaneous perichamber and abdominal spaces (spreading), and from the blood (disseminating) of infected mice. Both kininase and kinin receptor antagonist reduced animal mortality as a result of infection with strain A7436 and decreased the number of bacteria recoverable from the blood, but they were not associated with bacterial spreading. CONCLUSIONS: The results suggest that activation of the kinin system is involved in the breach of the vascular barrier that permits dissemination of P. gingivalis.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2003

Competitive binding inhibition enzyme-linked immunosorbent assay that uses the secreted aspartyl proteinase of Candida albicans as an antigenic marker for diagnosis of disseminated candidiasis.

The secreted aspartyl proteinases (Saps) of Candida albicans have been implicated as virulence factors associated with adherence and tissue invasion. The potential use of proteinases as markers of invasive candidiasis led us to develop a competitive binding inhibition enzyme-linked immunosorbent assay (ELISA) to detect Sap in clinical specimens. Daily serum and urine specimens were collected from rabbits that had been immunosuppressed with cyclophosphamide and cortisone acetate and infected intravenously with 10(7) C. albicans blastoconidia. Disseminated infection was confirmed by organ culture and histopathology. Although ELISA inhibition was observed when serum specimens from these rabbits were used, more significant inhibition, which correlated with disease progression, occurred when urine specimens were used. Urine collected as early as 1 day after infection resulted in significant ELISA inhibition (mean inhibition +/- standard error [SE] compared with preinfection control urine, 15.7% +/- 2.7% [P < 0.01]), and inhibition increased on days 2 through 5 (29.4% +/- 4.8% to 44.5% +/- 3.5% [P < 0.001]). Urine specimens from immunosuppressed rabbits infected intravenously with Candida tropicalis, Candida parapsilosis, Candida krusei, Cryptococcus neoformans, Aspergillus fumigatus, or Staphylococcus aureus were negative in the assay despite culture-proven dissemination. Nonimmunosuppressed rabbits receiving oral tetracycline and gentamicin treatment were given 2 x 10(8) C. albicans blastoconidia orally or intraurethrally to establish colonization of the gastrointestinal tract or bladder, respectively, without systemic dissemination; urine specimens from these rabbits also gave negative ELISA results. Dissemination to the kidney and spleen occurred in one rabbit challenged by intragastric inoculation, and urine from this rabbit demonstrated significant inhibition in the ELISA (mean inhibition +/- SE by day 3 after infection, 32.9% +/- 2.7% [P < 0.001]). The overall test sensitivity was 83%, the specificity was 92%, the positive predictive value was 84%, the negative predictive value was 91%, and the efficiency was 89% (166 urine samples from 33 rabbits tested). The specificity, positive predictive value, and efficiency could be increased to 97, 95, and 92%, respectively, if at least two positive test results were required for a true positive designation. The ELISA was sensitive and specific for the detection of Sap in urine specimens from rabbits with disseminated C. albicans infection, discriminated between colonization and invasive disease, reflected disease progression and severity, and has the potential to be a noninvasive means to diagnose disseminated candidiasis.

Animals↗

PubMed2002

Dissemination of Mycobacterium tuberculosis is influenced by host factors and precedes the initiation of T-cell immunity.

We report that dissemination of Mycobacterium tuberculosis in the mouse is under host control and precedes the initiation of T-cell immunity. Nine to eleven days after aerosol inoculation, M. tuberculosis disseminates to the pulmonary lymph nodes (LN), where M. tuberculosis-specific T cells are detected 2 to 3 days thereafter. This indicates that the initial spread of bacteria occurs via lymphatic drainage and that the acquired T-cell immune response is generated in the draining LN. Dissemination to peripheral sites, such as the spleen and the liver, occurs 11 to 14 days postinfection and is followed by the appearance of M. tuberculosis-specific T cells in the lung and the spleen. In all cases studied, dissemination to the LN or the spleen preceded activation of M. tuberculosis-specific T cells in that organ. Interestingly, bacteria disseminate earlier from the lungs of resistant C57BL/6 mice than from the lungs of susceptible C3H mice, and consequently, C57BL/6 mice generate an immune response to M. tuberculosis sooner than C3H mice generate an immune response. Thus, instead of spreading infection, early dissemination of M. tuberculosis may aid in the initiation of an appropriate and timely immune response. We hypothesize that this early initiation of immunity following inoculation with M. tuberculosis may contribute to the superior resistance of C57BL/6 mice.

Animals↗

PubMed2004

Comparison of disseminated and nondisseminated strains of Borrelia burgdorferi sensu stricto in mice naturally infected by tick bite.

Clinical isolates of Borrelia burgdorferi sensu stricto have been categorized into disseminated and nondisseminated groups based on distinct ribosomal spacer restriction fragment length polymorphism genotypes (RSTs). In order to determine whether transmission by tick bite would alter the dissemination dynamics and disease produced by distinct genotypes, disseminated isolates (RST1), nondisseminated isolates (RST3), and a standard laboratory strain (B-31) were established in a murine cycle utilizing infections transmitted by ticks. B-31 spirochetes circulated in the blood of inbred C3H/HeJ mice longer than in the blood of outbred mice. The majority of C3H mice exposed to RST1-infected ticks contained cultivable spirochetes in their blood for up to 17 days; in contrast, mice exposed to RST3 isolates demonstrated a precipitous decline in infection after day 7 postexposure. A quantitative PCR (q-PCR) assay demonstrated that the densities of spirochetes in blood were similar for the RST1 and RST3 isolates, except during the 2nd week postexposure, when the RST1 isolates displayed a markedly higher density in blood. Spirochete load in the heart and bladder of infected mice was measured by q-PCR at 8 weeks postexposure; the numbers of spirochetes in these tissues were similar for mice infected with either disseminated or nondisseminated strains. Similarly, histopathology samples of heart, bladder, and joint tissue obtained at 8 weeks postexposure did not reveal greater pathology in mice infected with the disseminated isolates. We conclude that although the spirochetemia induced by tick-transmitted disseminated isolates was more intense and of longer duration than that induced by nondisseminated isolates, the resultant pathologies produced by these strains were ultimately similar.

Animals↗

PubMed1996

Diagnosis of disseminated candidiasis by measurement of urine D-arabinitol/L-arabinitol ratio.

Relative amounts of D-arabinitol (fungal origin) and L-arabinitol (part of normal human metabolism) in urine were determined by gas chromatography and mass spectrometry from 61 hospitalized patients with hematological malignancies. Seventeen neutropenic patients with acute leukemia (with 53 samples) had disseminated yeast infections and received empiric antifungal therapy before confirmation of the diagnosis. Control groups consisted of 22 hematologic patients (76 samples) with either mucosal (n = 10) or urinary (n = 12) Candida colonization and 22 neutropenic patients (34 samples) with no clinical or laboratory signs of invasive yeast infection. Reference values were also obtained from 50 healthy adults (50 samples). The mean urine D-arabinitol/L-arabinitol ratio +/- standard deviation (range) was 16.91 +/- 41.79 (1.41 to 254.75) in patients with disseminated infection, 2.73 +/- 2.48 (1.11 to 19.00) in colonized hematologic patients, 2.12 +/- 0.84 (1.16 to 5.84) in neutropenic controls, and 1.95 +/- 0.34 (0.97 to 3.44) in healthy adults (P < 0.001 between patients with disseminated infection and all control groups). The sensitivity and specificity of the assay for detecting disseminated yeast infection were, respectively, 88 and 91% per patient (upper limit of normal, 4.00). Seventy-one percent of patients already expressed elevated values at the onset of empiric antifungal therapy. The diagnosis of disseminated infection was confirmed on average 21.7 days after the first elevation of the D-arabinitol/L-arabinitol ratio. The method contributes to diagnosis of disseminated yeast infection and helps in monitoring patients at risk, to support the initiation of antifungal therapy at an early stage of the disease.

Adolescent↗

PubMed2004

Peritoneal dissemination from central neurocytoma: case report.

OBJECTIVE: Central neurocytoma is a low grade tumor of neuroglial origin and a relatively new histological entity. Only a few cases have been reported and its biological behavior is still uncertain. Some cases have shown an aggressive behavior (local recurrence, malignant dedifferentiation or CSF dissemination) and challenged the initial view of its relative benignity. A case of central neurocytoma with peritoneal dissemination is presented. CASE: A six years-old boy with recurrent neurocytoma of III ventricle and left thalamus showed fast growth of tumor rest and ascites three and a half years after subtotal removal of the lesion. Tumor cells were identified in the ascitic fluid and implanted in the peritoneum. Chemotherapy was initiated immediately after diagnosis of peritoneal dissemination (etoposide, carboplatin, doxorubicin and cyclophosphamide). The patient developed metabolic imbalance and respiratory failure due to rapid formation of ascitic fluid and died 3 days after the diagnosis of peritoneal dissemination was established. CONCLUSION: Central neurocytoma is a low grade tumor with low values of the proliferative index in the majority of cases. In spite of that, some tumors may present a very aggressive behavior and extraneural dissemination. Evaluation of proliferative index may be a guideline parameter for planning adjuvant therapies after surgical treatment in selected cases. Extraneural dissemination may occur in some cases specially in patients with ventriculoperitoneal shunt.

Antineoplastic Agents↗