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1.
J Helminthol ; 97: e5, 2023 Jan 13.
Article in English | MEDLINE | ID: mdl-36635102

ABSTRACT

This study describes changes in oxidative stress (OS) parameters in mice experimentally infected with Angiostrongylus costaricensis, which causes abdominal angiostrongyliasis. For this, 28 Swiss mice were used, divided into two groups (G1 and G2), with 14 animals each. Of these, eight were infected with ten infective larvae each, by gavage, and six were used as a control group. Mice from G1 and G2 were euthanized at 14 days and 24 days post-infection, respectively. Tissue samples were used for histopathological analysis and blood (serum) samples were taken to assess the levels of proteins, non-protein thiols (NPTs) and nitric oxide (NO), from centrifugation and subsequent collection of aliquots of the supernatant. Among OS parameters, infected mice in both groups had higher NO levels than the control group, due to the presence of: eosinophil infiltrate in the liver and intestine; pancreatitis; and intestinal granuloma. However, the infected mice of both groups showed a reduction in the levels of NPTs, in relation to the control group, due to the presence of: eosinophilic infiltrate in the liver and intestine; and intestinal granuloma. Our results suggest that A. costaricensis infection has important effects on the intestine, liver and pancreas, and the analyses were performed from the tissue of these organs. The mechanisms for these changes are related to the decrease in the body's main antioxidant defences, as demonstrated by the reduction of NPTs, thus contributing to the development of more severe tissue damage. Thus, the objective of the present study was to evaluate the relationship between histopathological lesions and markers for OS.


Subject(s)
Angiostrongylus , Strongylida Infections , Mice , Animals , Granuloma , Oxidative Stress
2.
Br Poult Sci ; 61(6): 640-645, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32901508

ABSTRACT

1. Salmonella Gallinarum (SG) infections cause fowl typhoid, which leads to important economic losses. Multidrug resistance (MDR) and the capacity for bacteria to form biofilms could play an important role in the persistence of SG in poultry flocks resulting in intermittent disease outbreaks. The aim of the following study was to assess the lytic activity of two new bacteriophages (Salmonella phages UPF_BP1 and UPF_BP2) against MDR and biofilm-forming SG. 2. Forty-six strains of SG, isolated in 2015, were characterised by antimicrobial resistance, biofilm formation profiles and susceptibility to two new bacteriophages. 3. Of these strains, 24% were multidrug resistant and more than 80% formed biofilm, with no statistical difference between incubation temperatures (42°C or 22°C). With regard to the lytic activity of the phages, 85% of strains were susceptible to at least one phage. Of these, 74% were lysed by both phages, including MDR and biofilm producing strains. 4. The use of salmonella phages UPF_BP1 and UPF_BP2 were shown to be promising alternatives for the biological control of fowl typhoid.


Subject(s)
Bacteriophages , Poultry Diseases , Salmonella Infections, Animal , Salmonella enterica , Animals , Biofilms , Chickens , Poultry
4.
Clin Microbiol Infect ; 25(10): 1233-1238, 2019 Oct.
Article in English | MEDLINE | ID: mdl-30802651

ABSTRACT

OBJECTIVES: To evaluate the impact of false-positive IgM immunoblots on Lyme disease treatment and case reporting in a large healthcare system. METHODS: We obtained the results of all Lyme disease serological tests ordered at U.S. Air Force healthcare facilities in the USA between January 2013 and December 2017. We conducted chart reviews to adjudicate positive IgM immunoblots (from two-tier and independent testing) as true positives or false positives using established criteria, and we assessed whether these cases were reported to the U.S. Department of Defense surveillance system. RESULTS: Of the 18 410 serum tests (17 058 immunoassays and 1352 immunoblots) performed on 15 928 unique individuals, 249/1352 (18.4%) IgM immunoblots were positive. After excluding repeat tests, insufficiently documented cases, and participants with a history of Lyme disease, 212 positive IgM immunoblot cases were assessed. A total of 113/212 (53.3%) were determined to be false positives. Antibiotics were prescribed for Lyme disease for 97/99 (98.0%) participants with a true-positive test and 91/113 (80.5%) participants with a false-positive test. The number of false-positive cases reported to the surveillance system was identical to the number of unreported true-positive cases (n = 44). CONCLUSIONS: Lyme disease serological tests were overused in a large healthcare system, and positive results were frequently misinterpreted, leading to misdiagnosis and widespread antibiotic misuse. Underreporting of true-positive cases was offset by overreporting of false-positive cases, suggesting that the discrepancy between the reported incidence and true incidence of Lyme disease may not be as significant as previously assumed.


Subject(s)
Lyme Disease/diagnosis , Lyme Disease/epidemiology , Medical Overuse/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Bacterial/blood , Child , Child, Preschool , False Positive Reactions , Female , Humans , Immunoblotting/methods , Immunoglobulin M/blood , Incidence , Infant , Male , Middle Aged , Military Personnel , Retrospective Studies , Serologic Tests/methods , United States/epidemiology , Young Adult
5.
Water Sci Technol ; 77(3-4): 739-747, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29431719

ABSTRACT

Dieldrin and DDx removal through wastewater treatment, ozonation, and microfiltration was assessed for a water reuse project for groundwater replenishment in Monterey, California, USA. Full-scale sampling was conducted at the wastewater treatment plant, and physical wastewater treatment processes, ozonation, and microfiltration were tested at the bench scale. Removals observed through wastewater treatment, ozonation, and microfiltration were 84%, 44% to 63%, and 97% to 98%, respectively, for dieldrin, and 93%, 36% to 48%, and 92% to 94% for DDx. These were sufficient to meet California Ocean Plan water quality objectives after wastewater treatment alone. Levels in the secondary effluent, ahead of ozonation, microfiltration, reverse osmosis and advanced oxidation in the advanced water purification facility, met drinking water standards. Removal of dieldrin and DDx through wastewater treatment occurred by physical treatment processes; removal through the full-scale wastewater treatment plant, which included biological and physical treatment processes, matched removal through the physical bench-scale wastewater treatment processes. Dieldrin and DDx removal correlated with removal of volatile suspended solids, suggesting that volatile suspended solids could be used as an indicator for pesticide removal through wastewater treatment. Dieldrin and DDx concentrations were highest in the solids contact process, where biomass is accumulated for carbon removal.


Subject(s)
Dichlorodiphenyl Dichloroethylene/chemistry , Dieldrin/chemistry , Ozone/chemistry , Pesticides/chemistry , Waste Disposal, Fluid/methods , Water Pollutants, Chemical/chemistry , Biomass , Filtration , Wastewater/chemistry , Water Purification/methods
6.
Int J Obes (Lond) ; 37(10): 1407-12, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23357956

ABSTRACT

BACKGROUND: The macrogeographic distribution of obesity in the United States, including the association between elevation and body mass index (BMI), is largely unexplained. This study examines the relationship between obesity and elevation, ambient temperature and urbanization. METHODS AND FINDINGS: Data from a cross-sectional, nationally representative sample of 422603 US adults containing BMI, behavioral (diet, physical activity, smoking) and demographic (age, sex, race/ethnicity, education, employment, income) variables from the 2011 Behavioral Risk Factor Surveillance System were merged with elevation and temperature data from WorldClim and with urbanization data from the US Department of Agriculture. There was an approximately parabolic relationship between mean annual temperature and obesity, with maximum prevalence in counties with average temperatures near 18 °C. Urbanization and obesity prevalence exhibited an inverse relationship (30.9% in rural or nonmetro counties, 29.2% in metro counties with <250000 people, 28.1% in counties with population from 250000 to 1 million and 26.2% in counties with >1 million). After controlling for urbanization, temperature category and behavioral and demographic factors, male and female Americans living <500 m above sea level had 5.1 (95% confidence interval (CI) 2.7-9.5) and 3.9 (95% CI 1.6-9.3) times the odds of obesity, respectively, as compared with counterparts living ≥ 3000 m above sea level. CONCLUSIONS: Obesity prevalence in the United States is inversely associated with elevation and urbanization, after adjusting for temperature, diet, physical activity, smoking and demographic factors.


Subject(s)
Body Mass Index , Climate , Diet , Obesity/epidemiology , Physical Fitness , Urbanization , Adult , Demography , Female , Geographic Information Systems , Humans , Male , Obesity/genetics , Population Surveillance , Prevalence , United States/epidemiology
7.
Heart ; 90(11): 1299-302, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15486126

ABSTRACT

OBJECTIVE: To evaluate the association between baseline homocysteine concentrations and restenosis rates in patients electively undergoing their first percutaneous coronary intervention (PCI) without stenting. DESIGN: Prospective, single centre, observational study. SETTING AND PATIENTS: Patients electively undergoing their first PCI without stenting at a tertiary referral centre between 1990 and 1998. METHODS: Blood samples were collected from all patients at baseline and assayed to determine the patients' homocysteine concentrations. Patients whose PCI was successful underwent repeat angiography at a median of 6.4 (interquartile range 6-6.8) months. Their baseline and follow up angiograms were compared by quantitative coronary angiography to assess the incidence of restenosis. For the analysis, the patients were divided into two groups based on whether their baseline homocysteine concentrations were above or below the median value. These two groups were compared to determine whether there was any association between their baseline homocysteine concentrations and the incidence of restenosis at six months. RESULTS: 134 patients had a successful first PCI without stenting (involving 200 lesions). At six month angiography, restenosis was observed in 33 patients (49.3%) with baseline homocysteine concentrations above the median value and in 31 patients (46.3%) with concentrations below the median value (p = 0.74). There was no difference in the percentage of lesions developing restenosis (38 (39.6%) v 40 (38.5%), respectively, p = 0.87) or late lumen loss (0.40 mm v 0.31 mm, respectively, p = 0.24). On multivariable analysis, there was no association between homocysteine concentrations and late lumen loss (r = -0.11, p = 0.11) or the percentage diameter stenosis at follow up (r = -0.07, p = 0.32). CONCLUSION: Baseline homocysteine concentrations were not associated with six month restenosis rates in patients electively undergoing their first PCI without stenting.


Subject(s)
Angioplasty, Balloon, Coronary/methods , Coronary Restenosis/blood , Coronary Stenosis/therapy , Homocystine/blood , Stents , Biomarkers/blood , Coronary Angiography/methods , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies
8.
Pac Symp Biocomput ; : 166-77, 2004.
Article in English | MEDLINE | ID: mdl-14992501

ABSTRACT

Part-of relations are central to anatomy. However, the definition, formalisation and use of part-of in anatomy ontologies is problematic. This paper surveys existing formal approaches, as well as the use of part-of in the Open Biological Ontologies (OBO) anatomies of model species. Based on this analysis, we propose a minimal ontology for anatomy which is expressed in the Semantic Web languages RDFS and OWL-Full. The paper concludes with a description of the context of this work in capturing cross-species tissue homologies and analogies.


Subject(s)
Computational Biology , Models, Anatomic , Animals , Programming Languages , Software
9.
J Clin Oncol ; 19(12): 3091-102, 2001 Jun 15.
Article in English | MEDLINE | ID: mdl-11408506

ABSTRACT

PURPOSE: The study goal was to improve outcome in children with rhabdomyosarcoma by comparing risk-based regimens of surgery, radiotherapy (RT) and chemotherapy. PATIENTS AND METHODS: Eight hundred eighty-three previously untreated eligible patients with nonmetastatic rhabdomyosarcoma entered the Intergroup Rhabdomyosarcoma Study-IV (IRS-IV) (1991 to 1997) after surgery and were randomized treatment by primary tumor site, group (1 to 3), and stage (I to III). Failure-free survival (FFS) rates and survival were the end points used in comparisons between randomized groups and between patient subgroups treated on IRS-III and IRS-IV. Most patients were randomized to receive vincristine and dactinomycin (VA) and cyclophosphamide (VAC, n = 235), or VA and ifosfamide (VAI, n = 222), or vincristine, ifosfamide, and etoposide (VIE, n = 236). Patients with group 3 tumors were randomized to receive conventional RT (C-RT) versus hyperfractionated RT (HF-RT). RESULTS: Overall 3-year FFS and survival were 77% and 86%, respectively. Three-year FFS rates with VAC, VAI, and VIE were 75%, 77%, and 77%, respectively (P =.42). No significant difference in outcome was noted with HF-RT versus C-RT (P =.85 and P =.90, respectively). Overall, patients with embryonal tumors benefited from intensive three-drug chemotherapy in IRS-IV (3-year FFS, 83%). The improvement was seen for patients with stage I or stage II/III, group 1/2 disease, many of whom received VA chemotherapy on IRS-III. Patients with stage 2/3, group 3 disease had similar outcomes on IRS-III and IRS-IV. Three-year FFS for the nonrandomized patient subsets was 75% with renal abnormalities; 81% for paratesticular, group 1 cases; and 91% for group 1/2 orbit or eyelid tumors. Patients with paratesticular primaries had poorer outcomes if they were more than 10 years old (3-year FFS, 63% v 90%). Myelosuppression occurred in most patients, but toxic deaths occurred in less than 1%. CONCLUSION: VAC and VAI or VIE with surgery (with or without RT), are equally effective for patients with local or regional rhabdomyosarcoma and are more effective for embryonal tumors than therapies used previously. Younger patients with group 1 paratesticular embryonal tumors and all patients with group 1/2 orbit or eyelid tumors can usually be cured with VA chemotherapy along with postoperative RT for group 2 disease.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Radiotherapy/methods , Rhabdomyosarcoma/therapy , Adolescent , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Child , Child, Preschool , Combined Modality Therapy/methods , Disease-Free Survival , Dose Fractionation, Radiation , Eyelid Neoplasms/mortality , Eyelid Neoplasms/pathology , Eyelid Neoplasms/therapy , Female , Humans , Infant , Male , Orbital Neoplasms/mortality , Orbital Neoplasms/pathology , Orbital Neoplasms/therapy , Prognosis , Retrospective Studies , Rhabdomyosarcoma/mortality , Rhabdomyosarcoma/pathology , Survival Rate , Testicular Neoplasms/mortality , Testicular Neoplasms/pathology , Testicular Neoplasms/therapy
10.
Cancer Chemother Pharmacol ; 47(3): 211-21, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11320664

ABSTRACT

PURPOSE: To develop a highly reproducible model of disseminated childhood neuroblastoma in mice to allow secondary evaluation of therapeutics against microscopic disseminated disease. METHODS: CB17/Icr SCID were injected i.v. with 10(3) to 5 x 10(6) human NB-1691 neuroblastoma cells. NB-1691 cells were detected by PCR for synaptophysin and tyrosine hydroxylase in peripheral blood, and bone marrow. Therapeutic studies evaluated topotecan and vincristine as single agents or in combination. Topotecan was administered i.v. daily for 5 days on two consecutive weeks. Courses were repeated every 21 days for three cycles. Vincristine (1 mg/kg) was administered i.v. every 7 days for nine consecutive weeks. Treatment started 11-21 days after tumor cell inoculation. RESULTS: Following injection of > or = 1 x 10(5) cells 100% of mice developed disease. Mice inoculated with 10(7) cells survived a median of 42 days. Survival time was a linear function of the cell inoculum. At autopsy, gross tumor was routinely detected in many organs in particular liver, ovaries, kidneys and adrenals. NB-1691 cells were detected by PCR in peripheral blood, and bone marrow. Immunohistochemical staining showed that lesions were strongly positive for synaptophysin, chromogranin A and negative for leukocyte common antigen. Topotecan (0.6 mg/kg) alone extended median survival from 44 days (controls) to 95 days. When treatment was started 21 days after inoculation of NB-1691 cells, topotecan extended median survival from 39 days (controls) to 91 and 99 days at dose levels of 0.3 and 0.6 mg/kg, respectively. Vincristine (1 mg/kg) extended survival by a median of 9.5 days. In combination with vincristine (1 mg/kg), median survival was increased to 141 days (topotecan 0.6 mg/kg) and 159 days (topotecan 1.0 mg/kg). CONCLUSION: This model of disseminated neuroblastoma is highly reproducible. As this model may more closely simulate childhood disease it may be a valuable adjunct in developing new approaches to advanced stage, poor prognosis neuroblastoma.


Subject(s)
Disease Models, Animal , Neuroblastoma , Animals , Antineoplastic Agents/therapeutic use , Antineoplastic Agents, Phytogenic/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Mice , Mice, SCID , Neuroblastoma/drug therapy , Neuroblastoma/pathology , Topotecan/therapeutic use , Tumor Cells, Cultured , Vincristine/therapeutic use
11.
J Am Dent Assoc ; 132(12): 1702-4, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11780989

ABSTRACT

BACKGROUND: Unintended intravascular injections from inferior alveolar nerve blocks result in frustrating complications, both systemically and locally. It is imperative that the dentist diagnose the complication and treat it appropriately. Sometimes, several reactions occur simultaneously. CASE DESCRIPTION: The authors present a case report that illustrates some of the many complications resulting from inferior alveolar nerve block injections. In this case, complications developed from intra-arterial injection of local anesthetic. The facial skin, intraoral structures and eye were affected. Within 60 minutes of the injection, all structures returned to their normal state. Prompt diagnosis and reassurance usually calm the patient. CLINICAL IMPLICATIONS: Even when clinicians use the utmost care, by aspirating before the injection and noting anatomical landmarks, intra-arterial injections can occur during inferior alveolar nerve blocks. Fortunately, permanent damage to nerves, facial and oral tissues, and eyes is rare. The practitioner should diagnose and treat the problems appropriately to avoid any irreversible complications.


Subject(s)
Face/blood supply , Hypesthesia/etiology , Injections, Intra-Arterial/adverse effects , Medication Errors , Nerve Block/adverse effects , Adult , Anesthetics, Local/administration & dosage , Epinephrine/administration & dosage , Face/innervation , Female , Humans , Vasoconstrictor Agents/administration & dosage
12.
Acad Emerg Med ; 7(11): 1303-10, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11073483

ABSTRACT

OBJECTIVE: A computer-based system to apply trauma resuscitation protocols to patients with penetrating thoracoabdominal trauma was previously validated for 97 consecutive patients at a Level 1 trauma center by a panel of the trauma attendings and further refined by a panel of national trauma experts. The purpose of this article is to describe how this system is now used to objectively critique the actual care given to those patients for process errors in reasoning, independent of outcome. METHODS: A chronological narrative of the care of each patient was presented to the computer program. The actual care was compared with the validated computer protocols at each decision point and differences were classified by a predetermined scoring system from 0 to 100, based on the potential impact on outcome, as critical/noncritical/no errors of commission, omission, or procedure selection. RESULTS: Errors in reasoning occurred in 100% of the 97 cases studied, averaging 11.9/case. Errors of omission were more prevalent than errors of commission (2. 4 errors/case vs 1.2) and were of greater severity (19.4/error vs 5. 1). The largest number of errors involved the failure to record, and perhaps observe, beside information relevant to the reasoning process, an average of 7.4 missing items/patient. Only 2 of the 10 adverse outcomes were judged to be potentially related to errors of reasoning. CONCLUSIONS: Process errors in reasoning were ubiquitous, occurring in every case, although they were infrequently judged to be potentially related to an adverse outcome. Errors of omission were assessed to be more severe. The most common error was failure to consider, or document, available relevant information in the selection of appropriate care.


Subject(s)
Abdominal Injuries/diagnosis , Cardiopulmonary Resuscitation/methods , Diagnosis, Computer-Assisted/statistics & numerical data , Medical Errors/statistics & numerical data , Thoracic Injuries/diagnosis , Trauma Centers/standards , Wounds, Penetrating/diagnosis , Abdominal Injuries/therapy , Cardiopulmonary Resuscitation/adverse effects , Diagnosis, Computer-Assisted/adverse effects , Diagnosis, Computer-Assisted/methods , Female , Hospitals, University , Humans , Incidence , Injury Severity Score , Male , Philadelphia , Reproducibility of Results , Retrospective Studies , Sensitivity and Specificity , Statistics as Topic , Thoracic Injuries/therapy , Trauma Centers/statistics & numerical data , Wounds, Penetrating/therapy
13.
Proc AMIA Symp ; : 620-4, 2000.
Article in English | MEDLINE | ID: mdl-11079958

ABSTRACT

This paper presents TraumaSCAN, a prototype computer system for assessing the effects of penetrating trauma to the chest and abdomen. TraumaSCAN combines geometric reasoning about potentially injured anatomic structures with (probabilistic) diagnostic reasoning about the consequences of these injuries. We also present results obtained from testing TraumaSCAN retrospectively on 26 actual gunshot wound cases.


Subject(s)
Computer Simulation , Models, Anatomic , Neural Networks, Computer , Wounds, Gunshot/diagnosis , Bayes Theorem , False Positive Reactions , Humans , Image Processing, Computer-Assisted , Probability , Retrospective Studies , User-Computer Interface , Wounds, Penetrating/diagnosis
14.
J Am Coll Cardiol ; 35(6): 1516-24, 2000 May.
Article in English | MEDLINE | ID: mdl-10807455

ABSTRACT

OBJECTIVES: To evaluate the corrected Thrombolysis in Myocardial Infarction (TIMI) frame count (CTFC) as a predictor of late survival after myocardial infarction. BACKGROUND: Thrombolysis in Myocardial Infarction flow grades predict late survival after myocardial infarction. The CTFC provides a more reproducible measurement of infarct-related artery blood flow than the TIMI flow grade, and has been linked to 30-day outcomes, but it has not yet been established how the CTFC correlates with late survival. METHODS: Of 1,001 patients with acute myocardial infarction presenting within 4 h of symptom onset, 882 underwent angiography at approximately three weeks. Infarct artery flow was assessed, blinded to clinical outcomes, according to the CTFC and TIMI flow grade. Late cardiac mortality and survival were determined in 97.5% of patients. RESULTS: The mean CTFC was 40 +/- 29 in 644 patent infarct arteries (median, 34 [interquartile range, 24 to 47]). The CTFC, assessed as a continuous univariate variable, was found to be a predictor of five-year survival, as was the TIMI flow grade (both p < 0.001). On multivariate analysis, factors associated with five-year survival included the ejection fraction or end-systolic volume index (both p < 0.001); exercise duration (p = 0.005), age (p = 0.008), diabetes (p = 0.02) and CTFC (p = 0.02) or TIMI flow (p = 0.02). The same factors, except for the CTFC and TIMI flow grade, were predictors of 10-year survival. CONCLUSIONS: The CTFC three weeks after myocardial infarction was an independent predictor of five-year survival, but not 10-year survival. Although the CTFC provided additional prognostic information within TIMI flow grades, its superiority was not demonstrated.


Subject(s)
Myocardial Infarction/drug therapy , Thrombolytic Therapy , Adult , Aged , Blood Flow Velocity/drug effects , Coronary Angiography/drug effects , Coronary Circulation/drug effects , Female , Follow-Up Studies , Humans , Male , Middle Aged , Myocardial Infarction/mortality , Randomized Controlled Trials as Topic , Streptokinase/administration & dosage , Survival Rate , Tissue Plasminogen Activator/administration & dosage , Treatment Outcome
15.
Pediatr Dev Pathol ; 3(3): 290-300, 2000.
Article in English | MEDLINE | ID: mdl-10742419

ABSTRACT

Ectomesenchymomas (EM) are rare malignant neoplasms usually consisting of rhabdomyosarcoma (RMS) with a neural component. Only 21 cases have been previously reported. Here we extend the clinicopathologic spectrum of EM by describing our findings in 15 cases. Only 5 patients were infants; 10 were < or =3 years old and 5 were > or =6 years old. No male predilection was observed; 7 were female. The originating institutional diagnoses were; RMS (12), undifferentiated sarcoma (1), or EM (2), suggesting underdiagnosis of this entity. The primary tumor sites included external genital (5), pelvis/abdomen (6), head and neck (3), and extremity (1). The size of the primary neoplasm was usually > or =5 cm at diagnosis but dissemination only occurred in a minority. Local infiltration was not uncommon. These neoplasms were typically multilobate, thinly encapsulated, hemorrhagic, and necrotic. Light microscopic features were highly variable, but embryonal RMS with scattered or clustered ganglion cells, often in lacunae, was characteristic. In some cases, primitive neuroblastic or neuroectodermal areas were found and/or a component of alveolar RMS was seen. Focal anaplasia was occasionally observed. Mitotic activity appears higher than previously appreciated and some necrosis was invariably present. Electron microscopy was performed in 11 cases, which confirmed skeletal muscle +/- neural differentiation. Cytogenetic studies performed in five cases revealed no specific abnormality. Monoclonal neuron-specific enolase was the best marker of ganglion cells and primitive neural elements. MIC-2 (CD99) membrane expression was not definitively present in any of the six cases examined. A number of the above parameters appear to be of some prognostic significance, but overall, these neoplasms appear to have a similar outcome as would be predicted for their RMS element alone (exclusive of any neural component), with respect to the RMS subtype, age of the patient, and anatomic location of the neoplasm.


Subject(s)
Rhabdomyosarcoma/diagnosis , Abdominal Neoplasms/diagnosis , Adolescent , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Immunohistochemistry , Infant , Male , Muscle Neoplasms/diagnosis , Pelvic Neoplasms/diagnosis , Phosphopyruvate Hydratase/analysis , Retrospective Studies , Rhabdomyosarcoma/metabolism , Rhabdomyosarcoma/pathology , Survival Rate , Synaptophysin/analysis , Urogenital Neoplasms/diagnosis , Urogenital Neoplasms/metabolism , Urogenital Neoplasms/pathology
17.
J Am Coll Cardiol ; 34(1): 62-9, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10399993

ABSTRACT

OBJECTIVES: The purpose of this study was to determine whether the mortality benefit of intravenous streptokinase administered within 4 h of the onset of acute myocardial infarction is maintained at 12 years, and whether Thrombolysis in Myocardial Infarction (TIMI) flow grades independently influence late survival. BACKGROUND: Treatment with reperfusion therapies and achievement of TIMI 3 flow are associated with increased short- and medium-term survival after infarction. Whether infarct artery flow independently influences survival more than five years after infarction is unknown. METHODS: The late survival of patients randomized to receive either streptokinase (1,500,000 IU over 30 to 60 min) or a matching placebo within 4 h of symptom onset in 1984-1986 was determined. Angiography was performed in surviving patients at three to four weeks, and TIMI flow grades were assessed blind to randomization and outcomes. The late vital status was determined in 99% of patients. RESULTS: Patients randomized to receive streptokinase (n = 107) had improved survival compared with those randomized to placebo (n = 112) at five years (84% vs. 70%; p = 0.023) and 12 years (66% vs. 51%; p = 0.022). At five years 94% of patients with TIMI grade 3 flow, 81% of those with TIMI grade 2 flow and 72% of those with TIMI grade 0-1 flow survived (p = 0.005). At 12 years 72% of patients with TIMI 3, 67% of those with TIMI 2 and 54% of those with TIMI 0-1 flow survived (p = 0.023). Multivariate analysis identified the ejection fraction (p = 0.014), exercise duration (p = 0.013) and TIMI 3 flow (p = 0.04 compared with TIMI 0-2 flow) as important factors for five-year survival. At 12 years multivariate predictors of late survival were the ejection fraction (p = 0.006), exercise duration (p = 0.003) and myocardial score (p = 0.013). The end-systolic volume index was similar to the ejection fraction as a predictor of survival at five and 12 years. CONCLUSIONS: The survival benefits of streptokinase persist for 12 years after infarction. TIMI flow at three to four weeks is an independent predictor of five-year survival.


Subject(s)
Fibrinolytic Agents/therapeutic use , Myocardial Infarction/drug therapy , Myocardial Infarction/mortality , Streptokinase/therapeutic use , Thrombolytic Therapy , Actuarial Analysis , Aged , Coronary Vessels/physiopathology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Myocardial Infarction/physiopathology , Randomized Controlled Trials as Topic , Regional Blood Flow , Survival Analysis , Treatment Outcome , Ventricular Function
18.
Semin Radiat Oncol ; 9(2 Suppl 1): 77-84, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10210544

ABSTRACT

Preoperative chemotherapy and chemoradiation protocols are generally associated with high clinical response rates but limited pathologic responses for large primary tumors. We have initiated a prospective phase II study of weekly paclitaxel and carboplatin plus concurrent, fractionated external-beam radiation, followed by organ-preserving or function-restorative surgery (when applicable to maximize locoregional tumor control). Operable patients staged by triple endoscopy received a percutaneous gastrostomy and vigorous dental and nutritional support during therapy. Paclitaxel 60 mg/m2 and carboplatin at an area under the concentration-time curve of 1 were administered weekly with radiation therapy 45 Gy, with repeat biopsy of the primary site at 5 weeks. Patients with a positive biopsy had definitive surgery within 4 to 5 weeks. Patients with a negative biopsy received 3 additional weeks of radiation therapy, to a total dose of 72 Gy plus paclitaxel and carboplatin. Forty-three patients were enrolled, including 33 men and 10 women ranging in age from 37 to 81 years. Fourteen patients had stage III disease, 19 patients had stage IVA disease, and 10 patients had stage IVB disease. Sites of disease included the floor of the mouth (n = 8), tongue (n = 8), oropharynx (n = 5), hypopharynx (n = 4), larynx (n = 12), palate-tonsil (n = 2), unknown primary (n = 3), and nasal cavity (n = 1). Of 38 patients evaluable for primary response (two patients had unknown primary tumor, two patients failed to complete the chemoradiation protocol, and one patient was evaluable for toxicity only), 18 patients had a complete clinical response and 20 patients had a partial response; the overall clinical response rate was 100%. A pathologic clinical response at the primary site occurred in 25 of these 38 patients (66%), who subsequently received completion radiation (67 to 72 Gy). After induction chemoradiation, 36 patients with N1-N3 nodes had neck dissection; seven had positive nodes (19%). Fourteen patients had residual cancer at the primary site at the time of the repeat biopsy. Sites of the lesions were the floor of the mouth/mandible (n = 4), nasal cavity/maxilla (n = 2), base of tongue (n = 2), and larynx (n = 6). All were resected with function-preserving reconstruction (two patients required total laryngectomy and one patient refused surgery). At a median follow-up of more than 16 months, progression-free and overall survival rates were 64% and 68%, respectively. Preoperative paclitaxel, carboplatin, and radiation was associated with a high clinical response rate at the primary site and a high level of organ preservation or functional restoration, if ablation was performed.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/radiotherapy , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/administration & dosage , Carboplatin/adverse effects , Combined Modality Therapy , Female , Head and Neck Neoplasms/surgery , Humans , Male , Middle Aged , Neoplasm Staging , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Postoperative Complications , Preoperative Care , Prospective Studies , Survival Analysis , Treatment Outcome
19.
Pediatr Dev Pathol ; 2(3): 275-85, 1999.
Article in English | MEDLINE | ID: mdl-10191352

ABSTRACT

This review chronicles the series of publications that were the result of the willingness of pathologists and clinicians in the United States to share their pathologic materials and clinical data on patients who were placed on treatment protocols for rhabdomyosarcoma and related tumors over an extended period of time. The availability of this database enabled pathologists and clinicians to study a tumor type that is rare in individual institutions, but occurs in large enough numbers to produce valid conclusions not otherwise possible. Furthermore, young investigators were challenged by this opportunity and were able to spend the necessary time to make new observations that, in retrospect, helped direct protocol designs that produced significant improvement in patient survival. The key factor in this process is the surrender of individual scientific prerogatives to a small number of investigators. It is also important to recognize that the pathologist component of these series of contributions is only a part of the entire effort. It takes an organization of gifted, dedicated experts in many disciplines working together. The investigators who served on the Intergroup Rhabdomyosarcoma Group over a 25-year period eminently fulfilled this.


Subject(s)
Pathology, Clinical/history , Rhabdomyosarcoma/history , Societies, Medical/history , Child , Fellowships and Scholarships/history , History, 20th Century , Humans , Rhabdomyosarcoma/pathology
20.
Heart ; 81(2): 128-33, 1999 Feb.
Article in English | MEDLINE | ID: mdl-9922346

ABSTRACT

OBJECTIVE: To assess whether the 90 minute corrected thrombolysis in myocardial infarction frame count (CTFC) in the infarct related artery predicts left ventricular function at 48 hours in patients with myocardial infarction treated with aspirin, streptokinase, and either heparin or Hirulog. DESIGN AND SETTING: Analysis of 251 patients with acute myocardial infarction enrolled in the international, multicentre Hirulog early reperfusion/occlusion (HERO-1) trial, who underwent both 90 minute coronary angiography and 48 hour left ventriculography. MAIN OUTCOME VARIABLES: The CTFC was determined in the infarct related artery 90 minutes after starting intravenous streptokinase (1.5 x 106 U over 30 to 60 minutes), and compared with indices of left ventricular function assessed by contrast ventriculography at 48 hours. RESULTS: A CTFC of 2 SD below normal (37% v 51%, p = 0.005), and trends towards higher left ventricular ejection fractions (60.9% v 58.2%, p = 0.11) and lower end systolic volumes (50.1 ml v 55.9 ml, p = 0.23). A CTFC of 2 SD below normal (41% v 52%, p = 0.025), a smaller end systolic volume (49.1 ml v 59.3 ml, p = 0.02), and a higher left ventricular ejection fraction (60.4% v 56.5%, p = 0.03). CONCLUSIONS: The 90 minute CTFC predicts left ventricular function at 48 hours following streptokinase. The CTFC associated with better ventricular function may be higher than values determined from a non-infarct population.


Subject(s)
Coronary Angiography , Fibrinolytic Agents/therapeutic use , Myocardial Infarction/diagnostic imaging , Streptokinase/therapeutic use , Thrombolytic Therapy , Ventricular Dysfunction, Left/diagnostic imaging , Female , Humans , Male , Middle Aged , Myocardial Infarction/drug therapy , Myocardial Infarction/physiopathology , Predictive Value of Tests , Prognosis , Regional Blood Flow , Time Factors
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