Bio

Academic Appointments


Administrative Appointments


  • Chief of Pathology and Laboratory Medicine Service, Palo Alto VA Health Care System (1977 - Present)

Professional Education


  • Medical Doctor, National University of Colombia (1952)

Research & Scholarship

Current Research and Scholarly Interests


Radiation Pathology: The study of radiation-induced cardiovascular disease was initiated in 1966 with the cooperation of the Radiotherapy and Cardiology Divisions. The clinical-pathological entity Radiation-Induced Heart Disease (RIHD) was defined and its relation to dose, time and fractionation was established. An animal model was developed. The pathogenesis of the myocardial component of RIHD was elucidated using sequential plastic sections, electron microscopy and autoradiography.

Radiation injury has been studied in other tissues, including renal, hepatic and pulmonary parenchyma. The morphological and functional effects of ionizing radiation on endothelial cells are being evaluated in vitro and in several species of mammals.

Cerebral malaria: Previous studies of human and murine cerebral malaria (CM) have been complemented in 1986-87 by establishing the role of cytokines -- particularly TNF -- in CM produced by infecting CBA/ca mice with Plasmodium berghei anka.

Angiogenesis: A simple in vivo model for the quantitative study of microvessel proliferation was developed in 1987: the implantable Disc Angiogenesis System (DAS). The inhibiting effect of ionizing radiation and therapeutic hyperthermia on angiogenesis has been demonstrated using the DAS in mice. The angiogenic agonist or antagonist impact of several cytokines and some other proteins is being evaluated in the DAS.

Publications

Journal Articles


  • The pathology of ionizing radiation as defined by morphologic patterns ACTA ONCOLOGICA Fajardo, L. F. 2005; 44 (1): 13-22

    Abstract

    This article presents a brief description of the effects of ionizing radiation in human tissues, as seen by the Pathologist. The lesions that occur in multiple organ/tissues will be discussed, dividing them into those that affect (a) the parenchyma or epithelia, (b) the stromal elements, and (c) the blood vessels. Since not all lesions fit into these patterns, the exceptions will be described as characteristic organ lesions. Unless specified otherwise the alterations presented are those that result from electromagnetic radiation (x-rays and gamma rays) as used for clinical radiation therapy. Most of the material presented will be delayed injury (i.e. months-to-years after exposure). The epithelial/parenchymal lesions include atrophy, necrosis, metaplasia, cellular atypia, dysplasia, and neoplasia. The common stromal lesions--the best recognized by pathologists--include fibrosis, fibrinous exudates, necrosis (with a paucity of cellular inflammatory exudates), and atypical fibroblasts. The vascular lesions are quite consistent: most often they affect the microvessels (capillaries, sinusoids) producing lethal and sublethal damage to the endothelial cells, with capillary rupture or thrombosis. Medium-size vessels show neointimal proliferation, fibrinoid necrosis, thrombosis, or acute arteritis. Damage in large vessels is less common; it occurs more in arteries than in veins and includes neointimal proliferation, atheromatosis, thrombosis and rupture (a dramatic complication). Some of the characteristic organ lesions are veno-occlusive liver disease, acute radiation pneumonitis, permanent bone marrow hypoplasia or aplasia, and colitis cystica profunda. Neoplasms are a well-recognized delayed complication of radiation and will not be described in detail. It is important to remember that there are no pathognomonic features of injuries produced by ionizing radiation. Nonetheless, although not specific individually, the combined features are characteristic enough to be recognized.

    View details for DOI 10.1080/0284186051007440

    View details for Web of Science ID 000227012500003

    View details for PubMedID 15848902

  • Lethal infection by a previously unrecognised metazoan parasite LANCET SantamariaFries, M., Fajardo, L. F., Sogin, M. L., Olson, P. D., Relman, D. A. 1996; 347 (9018): 1797-1801

    Abstract

    New microbial pathogens or variant clinical manifestations of known organisms may be first found in immunodeficient patients. An HIV-infected man developed a rapidly-enlarging abdominal mass, suggestive of a neoplasm, that subsequently invaded his liver and caused death. Initial studies showed unusual tissue morphology that could not be matched with any known disease process.Tissues obtained from biopsy at laparotomy and necropsy were studied by light microscopy, immunohistochemistry, electron microscopy, and broad-range ribosomal DNA-amplification and sequence analysis.Tissue lesions were characterised by peculiar cytoplasmic sacs containing minute cells with very prominent nucleoli. The pathological process was recognised as a parasitic infection, although its features were different from those of any known eukaryotic pathogen. Phylogenetic analysis of a 357 bp 18S rDNA sequence amplified directly from the involved tissue indicated that the causative agent was a previously-uncharacterised cestode.Fatal disease produced by this newly recognised cestode may not be limited to immunodeficient hosts. Awareness of this metazoan infection may allow early diagnosis-by morphology and DNA sequence analysis--and perhaps successful treatment of subsequent cases.

    View details for Web of Science ID A1996UU46900011

    View details for PubMedID 8667924

  • DUAL ROLE OF TUMOR-NECROSIS-FACTOR-ALPHA IN ANGIOGENESIS AMERICAN JOURNAL OF PATHOLOGY Fajardo, L. F., Kwan, H. H., Kowalski, J., Prionas, S. D., Allison, A. C. 1992; 140 (3): 539-544

    Abstract

    The role of tumor necrosis factor-alpha (TNF; cachectin) in angiogenesis has been controversial. In vitro TNF inhibits proliferation of endothelial cells (EC) whereas in the cornea it appears to stimulate vessel growth. The authors tested TNF in their recently developed disc angiogenesis system (DAS), designed to measure the proliferation of microvessels. The DAS, implanted subcutaneously in mice, was either fitted with a central pellet containing mouse recombinant TNF (mrTNF), or exposed to mrTNF delivered subcutaneously by an osmotic minipump. Low doses of mrTNF (0.01-1 ng) induced angiogenesis, which was maximum at 0.1 ng, whereas high doses (1, and 5 micrograms) inhibited it. Subcutaneous mrTNF delivered at the (high) rate of 15-60 ng/hr for 14 days inhibited angiogenesis. These results indicate bimodal, dose-dependent opposing effects and explain some of the in vitro versus in vivo paradoxical results. TNF (native or exogenous) may have opposing effects on microvessels of neoplasms and inflammatory reactions, depending on its local tissue concentrations.

    View details for Web of Science ID A1992HH12000003

    View details for PubMedID 1372154

  • The complexity of endothelial cells. A review. American journal of clinical pathology Fajardo, L. F. 1989; 92 (2): 241-250

    Abstract

    This review of the biology peculiar to endothelial cells (ECs) is based mainly on data available within the last decade. The functions described refer to angiogenesis, coagulation, and EC-platelet interaction, inflammation and immune response, synthesis of stromal components, vascular tone regulation, and miscellaneous metabolic activities. Emphasis is placed on the marked variability of ECs from tissue to tissue and from one species to another. This heterogeneity is evident morphologically, functionally, and in the response of ECs to injury.

    View details for PubMedID 2667329

  • TUMOR-NECROSIS-FACTOR (CACHECTIN) AS AN ESSENTIAL MEDIATOR IN MURINE CEREBRAL MALARIA SCIENCE Grau, G. E., Fajardo, L. F., PIGUET, P. F., ALLET, B., Lambert, P. H., VASSALLI, P. 1987; 237 (4819): 1210-1212

    Abstract

    Tumor necrosis factor, or cachectin (TNF-alpha), a protein with a wide range of biological activities, is produced mainly by macrophages and may be important in inflammatory processes. The role of TNF-alpha in the pathogenesis of cerebral malaria was investigated in a murine model. Most CBA mice infected with Plasmodium berghei anka die between days 6 and 14 with acute neurological manifestations unrelated to the level of parasitemia, whereas mice of some other strains have malaria of the same severity that ends in death after 3 to 4 weeks without neurological manifestations. The activity of serum TNF-alpha was considerably increased in CBA/Ca mice with cerebral malaria but not in Plasmodium berghei-infected mice that did not develop this complication. One injection of rabbit antibody to TNF-alpha on day 4 or 7 fully protected infected mice from cerebral malaria without modifying the parasitemia, whereas immunoglobulins from normal rabbit had no effect. In mice with cerebral malaria, the cerebral vessels showed focal accumulations of packed macrophages often containing infected erythrocytes; this lesion was not seen in mice treated with antibody to TNF-alpha or in untreated mice without cerebral malaria. These findings indicate that TNF-alpha has an important role in the pathogenesis of cerebral malaria in this murine model and suggest that local accumulation and activation of macrophages may lead to the predominance of lesions in the central nervous system.

    View details for Web of Science ID A1987J838900045

    View details for PubMedID 3306918

  • KINETICS OF EMT-6 CELLULAR SURVIVAL AFTER CURATIVE DOSES OF HYPERTHERMIA BULLETIN DU CANCER Hahn, G. M., Marmor, J. B., FAJARDO, L. J. 1978; 65 (4): 473-474

    View details for Web of Science ID A1978GF17600015

    View details for PubMedID 747803

  • COMBINED CARDIOTOXICITY OF ADRIAMYCIN AND X-RADIATION LABORATORY INVESTIGATION Fajardo, L. F., ELTRINGHAM, J. R., Stewart, J. R. 1976; 34 (1): 86-96

    Abstract

    Our previous studies have shown that x-radiation produces cardiac lesions. Likewise, adriamycin, a useful antineoplastic agent, is known to be cardiotoxic. Maximal "safe" doses have been established for each of these forms of therapy. Since combined therapy with adriamycin and radiation is being used for malignancies involving the mediastinum, it is important to know whether the combination of both agents is more cardiotoxic than either agent alone. In this study young New Zealand White rabbits were divided into five groups and given: (1) a single dose of x-radiation of 1600 rads in the cardiac area; (2) 167 mg. per sq. m. of adriamycin; (3) both raddiation and adriamycin at the same doses; (4) 255 mg. per sq. m. of adriamycin; (5) no treatment. Animals in the third (combined) group developed radiation and adriamycin lesions, the frequency and severity of which were greater than those in the single therapy groups at the same (low) doses. These observations suggest a synergistic effect of the two agents. If so, patients receiving combined treatment are at risk of developing severe carditis from doses of adriamycin and cardiac x-radiation today regarded as safe. Although neither one is specific, the light and electron microscopic lesions caused by x-radiation (myocardial capillary damage, pericarditis) were easily distinguished from those caused by adriamycin (myocyte damage). Both agents led to diffuse myocardial fibrosis. These morphologic characteristics may have clinical applications.

    View details for Web of Science ID A1976BC80700009

    View details for PubMedID 1246126

  • PATHOGENESIS OF RADIATION-INDUCED MYOCARDIAL FIBROSIS LABORATORY INVESTIGATION Fajardo, L. F., Stewart, J. R. 1973; 29 (2): 244-257

    View details for Web of Science ID A1973Q551300013

    View details for PubMedID 4724850

  • MALARIAL PARASITES IN MAMMALIAN PLATELETS NATURE Fajardo, L. F. 1973; 243 (5405): 298-299

    View details for Web of Science ID A1973P842500033

    View details for PubMedID 4582662

  • Clinical manifestations of noncoronary atherosclerotic vascular disease after moderate dose irradiation CANCER Patel, D. A., Kochanski, J., Suen, A. W., Fajardo, L. F., Hancock, S. L., Knox, S. J. 2006; 106 (3): 718-725

    Abstract

    Accelerated atherosclerosis and carotid stenosis are well-established risks occurring after high radiation doses that are used to treat cancers of the head and neck. Noncoronary vascular disease has been observed and may relate to more moderate dose irradiation.A search of patients treated for Hodgkin disease, non-Hodgkin lymphoma, or seminoma was performed to identify cases with noncoronary vascular complications after irradiation. These three groups were chosen because of the use of intermediate dose radiation and prevalence of long-term survivors. Individual patient records were reviewed to document the type and presentation of the stenosis and the clinical factors that may have contributed to this risk.Twenty-one patients were identified who developed disease in noncoronary arteries after treatment. The median time from irradiation to diagnosis of vascular stenosis was 15 years. Antecedent risk factors for vascular disease were prevalent. Five patients had disease identified by auscultation of bruits before an adverse clinical event occurred. Five patients died from complications related to their vascular disease, which included three deaths after stroke and two after small bowel infarction.Twelve cases arose at an atypically young age for atherosclerotic vascular disease and featured unusual clinical presentations. Nine cases identified occurred at an advanced aged and at a shorter median interval, making a causal relation to irradiation uncertain. Incorporating careful auscultation for bruits in followup evaluation of irradiated patients may identify individuals who are at risk for adverse vascular events. The potential for early vasculopathy in individuals exposed to intermediate dose irradiation suggests a need to manage dyslipidemia and reduce vascular risk factors throughout the posttreatment period.

    View details for DOI 10.1002/cncr.21636

    View details for Web of Science ID 000234822700028

    View details for PubMedID 16353211

  • The pathology of ionizing radiation as defined by morphologic patterns Acta Oncologica Fajardo L F 2005; 44: 13-22
  • Radiation-associated cardiovascular disease: Manifestations and management SEMINARS IN RADIATION ONCOLOGY Adams, M. J., Lipshultz, S. E., Schwartz, C., Fajardo, L. F., COEN, V., Constine, L. S. 2003; 13 (3): 346-356

    Abstract

    Irradiation of the heart incidental to the treatment of malignancies can cause a spectrum of cardiovascular complications. These include pericarditis, myocardial fibrosis, muscular dysfunction, valvular abnormalities, and conduction disturbances. Survivors of Hodgkin's disease and breast cancer survivors treated with radiotherapy after mastectomy appear to be the groups at highest risk for radiation-associated cardiovascular disease. Although modern techniques of chest radiotherapy have decreased its frequency by reducing the dose and volume of radiation exposure to the heart, survivors treated with radiation remain at increased risk of cardiovascular disease. The risk of fatal cardiovascular disease increases with younger age at treatment, longer follow-up, and higher dose volumes of exposure to the heart. Certain chemotherapeutic agents, such as anthracyclines, also increase the risk of damage to the heart. Cardiac damage associated with radiotherapy may be progressive. Screening of survivors may help identify those at highest risk for serious cardiovascular disease. The broad range of radiation-associated cardiovascular disease makes it necessary for survivors to be examined with multiple screening modalities, although data do not exist to support definitive recommendations on test frequency.

    View details for DOI 10.1016/S1053-4296(03)00026-2

    View details for Web of Science ID 000184670300017

    View details for PubMedID 12903022

  • Clinical significance of increased gelatinolytic activity in the rectal mucosa during external beam radiation therapy of prostate cancer INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Hovdenak, N., Wang, J. R., Sung, C. C., Kelly, T., Fajardo, L. F., Hauer-Jensen, M. 2002; 53 (4): 919-927

    Abstract

    Rectal toxicity (proctitis) is a dose-limiting factor in pelvic radiation therapy. Mucosal atrophy, i.e., net extracellular matrix degradation, is a prominent feature of radiation proctitis, but the underlying mechanisms are not known. We prospectively examined changes in matrix metalloproteinase (MMP)-2 and MMP-9 (gelatinase A and B) in the rectal mucosa during radiation therapy of prostate cancer, as well as the relationships of these changes with symptomatic, structural, and cellular evidence of radiation proctitis.Seventeen patients scheduled for external beam radiation therapy for prostate cancer were prospectively enrolled. Symptoms of gastrointestinal toxicity were recorded, and endoscopy with biopsy of the rectal mucosa was performed before radiation therapy, as well as 2 and 6 weeks into the treatment course. Radiation proctitis was assessed by endoscopic scoring, quantitative histology, and quantitative immunohistochemistry. MMP-2 and MMP-9 were localized immunohistochemically, and activities were determined by gelatin zymography.Symptoms, endoscopic scores, histologic injury, and mucosal macrophages and neutrophils increased from baseline to 2 weeks. Symptoms increased further from 2 weeks to 6 weeks, whereas endoscopic and cellular evidence of proctitis did not. Compared to pretreatment values, there was increased total gelatinolytic activity of MMP-2 and MMP-9 at 2 weeks (p = 0.02 and p = 0.004, respectively) and 6 weeks (p = 0.006 and p = 0.001, respectively). Active MMP-2 was increased at both time points (p = 0.0001 and p = 0.002). Increased MMP-9 and MMP-2 at 6 weeks was associated with radiation-induced diarrhea (p = 0.007 and p = 0.02, respectively) and with mucosal neutrophil infiltration (rho = 0.62).Pelvic radiation therapy causes increased MMP-2 and MMP-9 activity in the rectal mucosa. These changes correlate with radiation-induced diarrhea and granulocyte infiltration and may contribute to abnormal connective tissue remodeling in radiation proctitis.

    View details for Web of Science ID 000176925400016

    View details for PubMedID 12095558

  • Nicotine accelerates angiogenesis and wound healing in genetically diabetic mice AMERICAN JOURNAL OF PATHOLOGY Jacobi, J., Jang, J. J., Sundram, U., Dayoub, H., Fajardo, L. F., Cooke, J. P. 2002; 161 (1): 97-104

    Abstract

    Recently, we have discovered an endogenous cholinergic pathway for angiogenesis mediated by endothelial nicotinic acetylcholine receptors (nAChRs). Since angiogenesis plays a major role in wound repair, we hypothesized that activation of nAChRs with nicotine would accelerate wound healing in a murine excisional wound model. In genetically diabetic and control mice full-thickness skin wounds (0.8 cm) were created on the dorsum and topically treated over 7 days with either vehicle (phosphate-buffered saline, PBS) or nicotine (10(-8) mol/L, 10(-9) mol/L; each, n = 5). Wound size was measured over 14 days followed by resection, histological analysis, and quantitation of vascularity. In diabetic animals an agonist (epibatidine, 10(-10) mol/L) or antagonist (hexamethonium, 10(-4) mol/L) of nAChRs as well as the positive control basic fibroblast growth factor (bFGF, 25 microg/kg) were also tested. To further study the role of endothelial nAChRs in angiogenesis, we used an ex vivo vascular explant model. In diabetic mice wound healing was markedly impaired. Nicotine significantly accelerated wound healing as assessed by closure rate and histological score. The effects of nicotine were equal to bFGF and were mimicked by epibatidine and blocked by hexamethonium. Histomorphometry revealed increased neovascularization in animals treated with nicotine. Furthermore, capillary-like sprouting from vascular explants was significantly enhanced by nicotine. In conclusion, agonist-induced stimulation of nAChRs accelerates wound healing in diabetic mice by promoting angiogenesis. We have discovered a cholinergic pathway for angiogenesis that is involved in wound healing, and which is a potential target for therapeutic angiogenesis.

    View details for Web of Science ID 000176718300013

    View details for PubMedID 12107094

  • Dose-response study of intracoronary beta-radiation with 32P in balloon- and stent-injured coronary arteries in swine. Cardiovascular radiation medicine Kaluza, G. L., Raizner, A. E., Mazur, W., Schulz, D. G., Zymek, P. T., Nguyen-Ho, P., Tio, F. O., Fajardo, L. F., Ali, N. M. 2001; 2 (4): 225-230

    Abstract

    A dose-response study was performed in swine to investigate the vascular effects of 32P over a broad range of doses in order to define the therapeutic window of intracoronary radiotherapy (ICR) with 32P.A total of 131 porcine arteries were subjected to balloon injury or stenting followed by 0-36 Gy of ICR from a centered 32P source wire to 1 mm beyond lumen surface or a sham ICR procedure. Animals were euthanized at 4 weeks, and vessels were harvested for histomorphometry.In the balloon-injured arteries, doses of 7 and 9 Gy did not impact restenosis. At doses of 14-36 Gy, neointima was markedly reduced, with mild dilatation at the highest dose, 36 Gy. In the stent-injured arteries, the lowest dose of 9 Gy failed to reduce neointimal growth, while 14-26 Gy showed the most favorable response.ICR with 32P features a broad therapeutic window. Doses of 14-26 Gy to 1 mm beyond lumen surface provided an optimal combination of efficacy and safety. Doses of 7 and 9 Gy were generally ineffective, suggesting a minimum threshold for ICR with 32P to effectively inhibit restenosis.

    View details for PubMedID 12160764

  • Long-term effects of intracoronary beta-radiation in balloon and stent-injured porcine coronary arteries CIRCULATION Kaluza, G. L., Raizner, A. E., Mazur, W., Schulz, D. G., Buergler, J. M., Fajardo, L. F., Tio, F. O., Ali, N. M. 2001; 103 (16): 2108-2113

    Abstract

    The data on the long-term safety and efficacy of intracoronary beta-radiation in animal models are limited.A total of 30 coronary arteries in 15 swine were subjected to balloon or stent injury followed by beta-radiation from a centered 32P source (2000 cGy to 1 mm beyond lumen surface) or a sham radiation procedure. The animals received aspirin for 6 months and ticlopidine for 30 days. Five of the 10 animals subjected to radiation died (at 5 days, 7 days, 3 months [n = 2], and 4 months) as a result of layered, occlusive thrombus at the intervention site (3 stent and 2 balloon injury sites). No deaths occurred in the control group. In the surviving animals, balloon-injured and irradiated vessels showed a trend toward larger lumens than controls (2.15 +/- 0.17 versus 1.80 +/- 0.08 mm2, P=0.06) and larger external elastic lamina areas (3.32 +/- 0.21 versus 2.62 +/- 0.10 mm2, P=0.003). In the stent-injured vessels from surviving animals, lumen, neointimal, and external elastic lamina areas were 3.58 +/- 0.33, 3.16 +/- 0.35, and 8.12 +/- 0.42 mm2 for irradiated vessel segments; these values were not different from those in controls (3.21 +/- 0.15, 2.84 +/- 0.27, and 7.76 +/- 0.28 mm2, respectively). Histologically, healing was complete in most survivors, although intramural fibrin and hemorrhage were occasionally seen.In the long-term (6 month) porcine model of restenosis, the inhibition by intracoronary beta-radiotherapy of the neointimal formation that is known to be present at 1 month is not sustained. This lack of effect on neointimal formation after balloon and stent arterial injury is accompanied by subacute and late thrombosis that leads to cardiac death on a background of continuous aspirin but relatively brief ticlopidine treatment.

    View details for Web of Science ID 000168383300024

    View details for PubMedID 11319203

  • Acute radiation proctitis: A sequential clinicopathologic study during pelvic radiotherapy INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Hovdenak, N., Fajardo, L. F., Hauer-Jensen, M. 2000; 48 (4): 1111-1117

    Abstract

    Rectal toxicity is often dose limiting during pelvic radiation therapy. This prospective study examined the sequential development and associations of clinical, endoscopic, and histopathologic rectal toxicity during ongoing radiation therapy.Thirty-three patients with nongastrointestinal pelvic carcinomas underwent proctoscopy with biopsy before radiation therapy, after 2 weeks treatment, and toward the end of the treatment course (6 weeks). Symptoms of acute toxicity were recorded, and endoscopic changes were graded. Histologic changes in the surface epithelium, glandular layer, and lamina propria were assessed using an ad hoc scoring system. Macrophage accumulation was evaluated in anti-CD68 stained sections.Pretreatment endoscopy and biopsies were unremarkable. Clinical symptoms progressed toward the end of the treatment course. In contrast, endoscopic pathology was maximal at 2 weeks. Biopsies obtained during treatment exhibited atrophy of the surface epithelium, acute cryptitis, crypt abscesses, crypt distortion and atrophy, and stromal inflammation. Histologic changes, particularly those in the surface epithelium, were consistently more pronounced at 2 weeks than they were at 6 weeks.In contrast to clinical symptoms, endoscopic changes stabilize and histologic changes regress from the 2nd to the 6th week of treatment. These results may have implications for the design and timing of prophylactic and therapeutic interventions to reduce radiation proctitis.

    View details for Web of Science ID 000165238800026

    View details for PubMedID 11072170

  • Angiogenesis is impaired by hypercholesterolemia - Role of asymmetric dimethylarginine CIRCULATION Jang, J. J., Ho, H. K., Kwan, H. H., Fajardo, L. F., Cooke, J. P. 2000; 102 (12): 1414-1419

    Abstract

    Many angiogenic factors require endothelium-derived nitric oxide (NO) to exert their effects. Recently, an endogenous competitive antagonist of NO synthase has been characterized: asymmetric dimethylarginine (ADMA). Elevated plasma levels of ADMA reduce NO synthesis in hypercholesterolemia. Accordingly, we hypothesized that hypercholesterolemia impairs angiogenesis by an ADMA-dependent mechanism.Angiogenesis was assessed with the use of a disk angiogenesis system implanted subcutaneously in normal (E(+)) mice or apolipoprotein (apo)E-deficient hypercholesterolemic (E(-)) mice. After 2 weeks, the disks were removed, and the fibrovascular growth area was used as an index of angiogenesis. Basal and fibroblast growth factor-stimulated angiogenesis was impaired in E(-) mice, associated with an elevation in plasma ADMA. Oral administration of L-arginine reversed the impairment of angiogenesis in E(-) mice. By contrast, oral administration of L-nitroarginine (an exogenous antagonist of NO synthase) reduced angiogenesis. When added directly to the disk, ADMA dose-dependently inhibited basal and fibroblast growth factor-induced angiogenesis, an effect that was reversed by oral administration of L-arginine.The derangement of the NO synthase pathway that occurs in hypercholesterolemia is associated with an impairment of angiogenesis. The lipid-induced impairment of angiogenesis can be reversed by oral administration of L-arginine and can be mimicked in normocholesterolemic animals by administration of an NO synthase antagonist. The data are consistent with the hypothesis that ADMA is an endogenous inhibitor of angiogenesis.

    View details for Web of Science ID 000089335900014

    View details for PubMedID 10993861

  • Clinical and pathologic overlap in nonsteroidal anti-inflammatory drug-related small bowel diaphragm disease and the neuromuscular and vascular hamartoma of the small bowel AMERICAN JOURNAL OF SURGICAL PATHOLOGY Cortina, G., Wren, S., Armstrong, B., Lewin, K., Fajardo, L. 1999; 23 (11): 1414-1417

    Abstract

    Diaphragm disease (DD) is a radiographically subtle cause of small bowel obstruction and is part of the spectrum of diseases associated with nonsteroidal anti-inflammatory drug injury. The neuromuscular and vascular hamartoma (NMVH) is a nonepithelial hamartomatous, submucosally based proliferation of mature submucosal elements capable of causing small bowel obstruction. The authors report two patients in whom the clinical setting and gross pathology are that of DD, but the histologic characterization is identical to that described for NMVH. It is probable that in some patients the two diseases overlap so that some patients readily fit the criteria for both entities.

    View details for Web of Science ID 000083467900013

    View details for PubMedID 10555011

  • Is the pathology of radiation injury different in small vs large blood vessels? Cardiovascular radiation medicine Fajardo, L. F. 1999; 1 (1): 108-110

    View details for PubMedID 11272350

  • Despite its homology to angiostatin apolipoprotein(a) does not affect angiogenesis EXPERIMENTAL AND MOLECULAR PATHOLOGY Lou, X. J., Kwan, H. H., Prionas, S. D., Yang, Z. J., Lawn, R. M., Fajardo, L. F. 1998; 65 (2): 53-63

    Abstract

    Apolipoprotein(a) [apo(a)] contains a kringle domain(IV) homologous to that of angiostatin, a natural angiogenic inhibitor. Because of this structural similarity we suspected that apo(a) could be an inhibitor of angiogenesis. The possible role of apo(a) in microvascular proliferation was studied in an in vivo quantitative model, the disc angiogenesis system (DAS) and compared to angiostatin. Apo(a) and other test compounds were placed in the center of a polyvinyl alcohol foam disc that was implanted subcutaneously in mice. After 14 days, the disc was removed and vascular growth into the disc was measured. Apo(a) did not affect spontaneous vessel growth into the disc, while angiostatin suppressed this growth and basic fibroblast growth factor (bFGF) increased it. Additionally, apo(a) did not modify the vascular growth induced by bFGF. Transgenic mice expressing the human apo(a) gene were used to study the systemic effect of apo(a): neither an increase nor a decrease in vascular growth was detected. Our results suggest that apo(a) is unlikely to play a significant role in the control of angiogenesis. Furthermore, our experiments confirm the inhibitory effect of angiostatin not only on induced angiogenesis but also on baseline, spontaneous angiogenesis.

    View details for Web of Science ID 000077353000001

    View details for PubMedID 9828147

  • The nature of arterial restenosis after angioplasty. Editorial Int. J. Radiation Oncology Biol. Phys. Fajardo LF 1998; 40: 761-763
  • High dose rate intracoronary radiation for inhibition of neointimal formation in the stented and balloon-injured porcine models of restenosis: Angiographic, morphometric, and histopathologic analyses INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Mazur, W., Ali, M. N., Khan, M. M., DABAGHI, S. F., DeFelice, C. A., Paradis, P., Butler, E. B., Wright, A. E., Fajardo, L. F., French, B. A., Raizner, A. E. 1996; 36 (4): 777-788

    Abstract

    We examined the effects of intracoronary irradiation delivered at a high dose rate on neointimal hyperplasia after injury induced by two methods: balloon overstretch injury, and stent implantation in a porcine model of coronary restenosis.In 34 Hanford miniature swine, a segment of each coronary artery was targeted for injury and treatment. The artery segments were treated with 192Ir at doses of 10 Gy over 4 min (eight animals), 15 Gy over 6 min (nine animals), 25 Gy over 10 min (nine animals) or control (simulation wire only; eight animals). The treated segments were subjected to stent implantation (left anterior descending and right coronary artery) or balloon overstretch (circumflex) injury. Twenty-eight days later, repeat coronary angiography and sacrifice were done. Quantitative coronary angiography, morphometry, and extensive histopathologic analyses were carried out in a blinded fashion.The change in minimal lumen diameter from postinjury to presacrifice in the stent-injured left anterior descending was -0.79 +/- 0.34 (mean: +/- SD) mm in the control group, compared to -0.43 +/- 0.35 mm in the 15 Gy (p = 0.04) and -0.21 +/- 0.50 mm in the 25 Gy (p = 0.01) groups; and in the balloon-injured circumflex was -0.31 +/- 0.22 mm in the control group compared to -0.03 +/- 0.18 mm in the 10 Gy (p = 0.05) and 0.00 +/- 0.33 in the 15 Gy (p = 0.01) groups. Percent area stenosis in the left anterior descending was 36 +/- 9% in the control group compared to 18 +/- 12% in the 15 Gy (p = 0.003) and 11 +/- 11% in the 25 Gy (p < 0.001) groups; and in the circumflex was 16 +/- 10% in the control groups, compared to 5 +/- 5% in the 15 Gy (p = 0.02) and 2 +/- 2% in the 25 Gy (p = 0.009) groups. Histopathology showed a striking reduction in the amount of neointima in the irradiated arteries compared with control vessels. Other radiation effects were stromal fibrin exudate, thinning of the media, and adventitial fibrosis and leukocyte infiltration in the radiated arterial segments.High dose rate intracoronary irradiation with 192Ir effectively inhibits intimal proliferation after stent-induced as well as balloon-overstretch injury. This shorter treatment time (4 to 10 min) may provide a clinically practical approach to the prevention of restenosis after angioplasty.

    View details for Web of Science ID A1996VX99200002

    View details for PubMedID 8960503

  • Radiation and the coronary arteries: Friend or foe? INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Fajardo, L. F., Stewart, J. R. 1996; 36 (4): 971-972

    View details for Web of Science ID A1996VX99200030

    View details for PubMedID 8960531

  • Multifocal heterogeneity in villin and Ep-CAM expression in Barrett's esophagus INTERNATIONAL JOURNAL OF CANCER KUMBLE, S., Omary, M. B., Fajardo, L. F., Triadafilopoulos, G. 1996; 66 (1): 48-54

    Abstract

    Barrett's esophagus (BE) is a metaplastic change of the squamous esophageal epithelium to columnar gastric or intestinal-like epithelium. BE is associated with long-standing gastroesophageal reflux disease and carries an increased risk for dysplasia and adenocarcinoma. Little if any is known regarding the differentiation state of esophageal metaplasia and its relationship to carcinogenesis. In this study, we investigated the potential of villin, a cytoskeletal protein, and Ep-CAM, a glandular epithelial glycoprotein, to serve as markers for enterocytic differentiation in BE at the molecular level. Endoscopic mucosal biopsy samples of normal esophagus, BE, stomach and duodenum were collected from 23 patients with BE. Biopsies were analyzed for villin and Ep-CAM expression by immunoblotting, and in some cases for the presence of microvilli by electron microscopy. By mapping of BE segments in 6 patients, correlations were also made between the histologic evidence of metaplasia and villin expression. Villin was uniformly expressed in all duodenal samples but was not detected in normal esophagus and stomach. In BE biopsies, villin expression was limited to the subset of patients whose adjacent biopsies showed microvilli by electron microscopy. In several patients studied, however, the expression of villin and the epithelial glycoprotein Ep-CAM differed among various regions of esophageal metaplasia within the same patient. Mapping studies failed to reveal any correlation among histologic evidence of metaplasia, dysplasia and villin expression and confirmed the multifocal heterogeneity of villin expression in BE. Preliminary data of 4 adenocarcinoma patients studied showed that villin expression was absent in 3 and very low in 1 patient. Ep-CAM was highly expressed in all adenocarcinoma patients. Our results show that BE represents a complex epithelium with significant heterogeneity in antigen expression and ultrastructural morphologic features. This molecular heterogeneity supports the presence of different stages of differentiation within the same epithelium.

    View details for Web of Science ID A1996UB75100009

    View details for PubMedID 8608965

  • Transforming growth factor beta 1 induces angiogenesis in vivo with a threshold pattern LABORATORY INVESTIGATION Fajardo, L. F., Prionas, S. D., Kwan, H. H., Kowalski, J., Allison, A. C. 1996; 74 (3): 600-608

    Abstract

    The true role of transforming growth factor beta1 (TGFbeta) on angiogenesis is in question. Several in vitro studies have shown inhibition of proliferation and migration of endothelial cells (EC). However, some investigators have observed that TGFbeta stimulates the formation of EC tubes in vitro. Fewer in vivo studies have been performed, but these also show discrepancies: some report angiogenic induction and at least one reports inhibition. We used the disc angiogenesis system (DAS) to measure the in vivo effect of TGFbeta. Discs containing 1 ng to 2000 ng of TGFbeta were placed subcutaneously in mice, removed after a growth period of 14 days, measured by three different techniques, and compared with spontaneous growth controls and with positive controls containing prostaglandin El. Tritiated thymidine was used to determine proliferation of EC. The discs were also examined morphologically for patterns of vessel and stromal proliferation. The contribution of native TGFbeta to the spontaneous angiogenesis of wound healing was tested using a monoclonal anti-TGFbeta antibody. The combined effect of TGFbeta and fibroblast growth factor (bFGF) was studied by using suboptimal doses of both (500 ng and 10 microg, respectively). Although TGFbeta doses of 1 ng to 500 ng failed to induce angiogenesis, 1000 ng induced a significant level of angiogenesis which was maintained at 2000 ng. This effect was the same regardless of the method of quantification: centripetal growth of the vessels, size of fibrovascular growth area, or amount of incorporation of tritiated thymidine. The anti-TGFbeta antibody decreased the spontaneous vascular growth below the level of controls containing irrelevant IgG. The combination of TGFbeta and bFGF at suboptimal doses did not increase or decrease the angiogenic response. Discs containing TGFbeta showed more collagen and greater accumulation of neutrophils than control discs or discs containing other cytokines. In conclusion, TGFbeta1 is angiogenic in vivo, when it reaches a threshold of 1 microg, but is not angiogenic at doses of 1 to 500 ng. Endogenous TGFbeta contributes to spontaneous (wound healing) angiogenesis. At the suboptimal doses of TGFbeta and bFGF used, there is no evidence of a combined angiogenic effect. The angiogenic effect of TGFbeta is probably indirect, requiring recruitment of leukocytes that secondarily release angiogenic substances. This secondary effect may explain some of the discrepancies between the in vitro and in vivo effects of TGFbeta.

    View details for Web of Science ID A1996UB44300004

    View details for PubMedID 8600310

  • EORTC Late Effects Working Group. Overview of late effects normal tissues (LENT) scoring system. Radiotherapy and oncology Rubin, P., Constine, L. S., Fajardo, L. F., Phillips, T. L., Wasserman, T. H. 1995; 35 (1): 9-10

    View details for PubMedID 7569016

  • RTOG LATE EFFECTS WORKING GROUP - OVERVIEW - LATE EFFECTS OF NORMAL-TISSUES (LENT) SCORING SYSTEM INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Rubin, P., Constine, L. S., Fajardo, L. F., Phillips, T. L., Wasserman, T. H. 1995; 31 (5): 1041-1042

    View details for Web of Science ID A1995QU29500003

    View details for PubMedID 7713774

  • ENDOTHELIAL-CELLS AND HYPERTHERMIA INTERNATIONAL JOURNAL OF HYPERTHERMIA Fajardo, L. F., Prionas, S. D. 1994; 10 (3): 347-353

    Abstract

    Most radiation oncologists are aware of the effects of clinical hyperthermia on neoplastic cells. Its effects on blood vessels, however, are not as well recognized. Yet, since the 1960s a number of investigators have described and categorized the effects of hyperthermia on microvessels (in vivo), and on cultured endothelial cells (EC) (in vitro). Both EC and microvessels can be lethally damaged by the hyperthermia doses used as antineoplastic therapy. In vitro data indicate that capillary EC are moderately sensitive to hyperthermia. Proliferating EC are more thermosensitive suggesting that microvessels of malignant neoplasms (which contain many proliferating EC) are more affected than microvessels of normal tissues. This differential sensitivity of microvessels has also been observed in blood flow studies. Furthermore, hyperthermia inhibits angiogenesis. Thus, some of the antineoplastic effects of heat are caused by ischaemia due to obstruction or destruction of the tumour vessels or to inability to form new vessels. Sublethal EC damage can also be demonstrated, resulting in decreased synthesis of most proteins including adhesion molecules (as well as increased expression of a few such as heat shock proteins) and producing reversible loss of cytoskeletal elements. The therapeutic advantage provided by the higher thermal sensitivity of neoplastic vessels should be exploited further, perhaps by developing strategies specifically aimed to the tumour microvasculature.

    View details for Web of Science ID A1994NP47600006

    View details for PubMedID 7930800

  • BASIC MECHANISMS AND GENERAL MORPHOLOGY OF RADIATION-INJURY SEMINARS IN ROENTGENOLOGY Fajardo, L. F. 1993; 28 (4): 297-302

    View details for Web of Science ID A1993ME32700004

    View details for PubMedID 8272878

  • APPLICATION OF THE DISC ANGIOGENESIS SYSTEM TO TUMOR-INDUCED NEOVASCULARIZATION EXPERIMENTAL AND MOLECULAR PATHOLOGY Nelson, M. J., CONLEY, F. K., Fajardo, L. F. 1993; 58 (2): 105-113

    Abstract

    Solid tumors elaborate soluble substances that (directly or indirectly) induce angiogenesis by a step-wise process which ultimately results in a microvascular network that nourishes the growing tumor. To study angiogenesis induced by brain tumors we have used a rat glioma model. Modifying the disc angiogenesis system (DAS) we evaluated quantitatively the angiogenic response to cultured, live RT-2 rat glioma cells placed in the center of the discs. DAS were implanted in the subcutaneous tissue of rats and evaluated for vessel proliferation 2 weeks later. Recognition of vessels was greatly facilitated by the staining of their basement membrane using a polyclonal anti-collagen IV antibody. Experimental discs containing 10(3) or 10(5) glioma cells as well as positive control discs containing the agonist prostaglandin E1 consistently demonstrated greater vessel growth than negative controls (discs containing a balanced salt solution). The disc angiogenesis system is a useful tool for the measurement of angiogenic response to living tumor cell suspensions.

    View details for Web of Science ID A1993LC92600003

    View details for PubMedID 7684337

  • CHARACTERIZATION AND APPLICATIONS OF THE DISK ANGIOGENESIS SYSTEM EXPERIMENTAL AND MOLECULAR PATHOLOGY Kowalski, J., Kwan, H. H., Prionas, S. D., Allison, A. C., Fajardo, L. F. 1992; 56 (1): 1-19

    Abstract

    A model to study microvascular proliferation, the Disc Angiogenesis System (DAS), consists of a synthetic foam disc implanted subcutaneously in experimental animals. After a period of growth, usually 7 to 21 days, the disc is removed. Planar sections are used to measure and characterize the growth. Microvessels grow centripetally into the disc, together with fibroblasts. Concentric growth zones have been defined by light and electron microscopy. Moderate growth occurs spontaneously and is accelerated by angiogenic stimulants placed in the center of the disc. Morphometric analyses have shown that vessel growth is directly proportional to total fibrovascular growth, so the former can be quantified by procedures measuring the latter. These include manual projection of sections and computer-assisted digital image analysis, which is recommended for routine use. The proliferation of endothelial and other cells is determined by incorporation of tritiated thymidine, using scintillation counting and autoradiography. Using the DAS, well-established angiogenic agents such as basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), and prostaglandin E1 were found to increase proliferation of endothelial cells (EC) and microvessels. Heparin augmented the effect of bFGF. When used by itself heparin increased angiogenesis but not EC proliferation, in keeping with in vitro observations indicating that it stimulates migration but not proliferation of EC. Locally applied hyperthermia and ionizing radiation decreased angiogenesis, even when applied after the angiogenic stimulus. Systemic prostaglandin synthetase inhibitors antagonized the angiogenic effects of bFGF and EGF, in accordance with a postulated role of prostaglandins in the transduction of proliferative signals in microvascular EC. The DAS is easy to assemble and implant in small animals, including mice, which tolerate it well. Hence multiple discs can be used for each time or dose point, which allows reproducible measurements of vascular growth and increases statistical accuracy. Another advantage of the system is the capability of discriminating between proliferation and migration of EC and fibroblasts. The DAS can be used to test putative agonists or antagonists of angiogenesis. More generally, the DAS provides a model of wound healing, either uncomplicated or complicated by inflammation, and of angiogenic responses to solid tumors.

    View details for Web of Science ID A1992HK02700001

    View details for PubMedID 1372267

  • Cultured proliferating rat mammary epithelial cells. In vitro cellular & developmental biology Ehmann, U. K., OSBORN, R. C., Guzman, R. C., Fajardo, L. F. 1991; 27A (9): 749-754

    Abstract

    Normal epithelial cells from the rat mammary gland proliferated in culture when plated with lethally irradiated cells of the LA7 rat mammary tumor line. Proliferation of the normal rat cells occurred as the LA7 cells slowly died from the radiation. By labeling the cultures with 3H-thymidine it was determined that most of the proliferating rat cells were those adjacent to the LA7 feeder cells. The epithelial cells from the primary culture proliferated after subsequent passages if the cells were plated at each subculture with newly irradiated LA7 cells. If the cells were plated at a ratio of approximately 1:8 rat:LA7 a confluent layer of normal rat cells covered the plastic substrate after 6 to 7 wk. The cells have so far been carried up through Passage 7, which amounted to approximately 19 doublings in cell number, and still proliferate vigorously. The growth medium for this culture system was Dulbecco's modified Eagle's medium:Ham's F12 1:1 supplemented with fetal bovine serum, insulin, and antibiotics. The presence in the cells of keratin, desmosomes, and cell junctions attested to their epithelial origin. The cultures were composed of cells with diploid or near diploid chromosome numbers. Samples of the cultured cells were implanted into the cleared fat pads of nude mice. Most of the implants from Passage 2 formed normal mammary ductal structures, but the incidence of outgrowths decreased significantly with later passages until no outgrowths resulted from the implantation of cells from Passage 5. The one unusual, feeder-independent cell line that arose from a primary culture seemed to be immortal in culture, contained a hyperdiploid chromosome complement, and formed abnormal structures when implanted into cleared fat pads.

    View details for PubMedID 1717432

  • TUMOR-NECROSIS-FACTOR IN HUMAN-DISEASE WESTERN JOURNAL OF MEDICINE Fajardo, L. F., Grau, G. E. 1991; 154 (1): 88-89

    Abstract

    The Scientific Board of the California Medical Association presents the following inventory of items of progress in pathology. Each item, in the judgment of a panel of knowledgeable physicians, has recently become reasonably firmly established, both as to scientific fact and important clinical significance. The items are presented in simple epitome and an authoritative reference, both to the item itself and to the subject as a whole, is generally given for those who may be unfamiliar with a particular item. The purpose is to assist busy practitioners, students, researchers, or scholars to stay abreast of these items of progress in pathology that have recently achieved a substantial degree of authoritative acceptance, whether in their own field of special interest or another. The items of progress listed below were selected by the Advisory Panel to the Section on Pathology of the California Medical Association, and the summaries were prepared under its direction.

    View details for Web of Science ID A1991EU51100008

    View details for PubMedID 2024513

  • MECHANISM OF ANTITUMOR-ACTIVITY OF TUMOR-NECROSIS-FACTOR-ALPHA WITH HYPERTHERMIA IN A TUMOR-NECROSIS-FACTOR ALPHA-RESISTANT TUMOR JOURNAL OF THE NATIONAL CANCER INSTITUTE Srinivasan, J. M., Fajardo, L. F., Hahn, G. M. 1990; 82 (24): 1904-1910

    Abstract

    Cells from a radiation-induced fibrosarcoma (RIF-1) are exceedingly resistant to tumor necrosis factor alpha (TNF-alpha) in vitro. We tested whether the addition of mild hyperthermia (42.5 degrees C, 30 minutes) could enhance TNF-alpha activity against RIF-1 tumors growing in syngeneic hosts (C3H mice). TNF-alpha was administered intratumorally. Tumor cell killing essentially was not measurable following TNF-alpha, hyperthermia, or a combination of the two. Single-modality treatments also had no effect on tumor growth delay or on the x-ray dose (given 24 hours after the primary treatment) required to sterilize 50% of the tumors. The combination of TNF-alpha and hyperthermia, however, resulted in a marked increase in tumor doubling time and a highly significant reduction in the x-ray dose required to sterilize the tumors. Syngeneic lymph nodal lymphocytes and blood leukocytes did not appear to mediate the action of TNF-alpha on RIF-1 cells in vitro. Necrosis and hemorrhage were the most prominent histopathological alterations in the treated tumors. Electron microscopic studies 6 hours after therapy showed increased damage to capillary endothelial cells and accumulation of neutrophils in the capillaries of tumors treated with TNF-alpha with or without heat, suggesting that neutrophils may mediate the endothelial cell injury. These observations indicate a greater than additive tumoricidal effect of TNF-alpha with hyperthermia. Furthermore, they support the concept that the interaction between the two agents damages the vasculature, compromising the microcirculation and ultimately causing ischemic tumor necrosis.

    View details for Web of Science ID A1990EN05300013

    View details for PubMedID 2250311

  • EFFECTS OF X-IRRADIATION ON ANGIOGENESIS RADIATION RESEARCH Prionas, S. D., Kowalski, J., Fajardo, L. F., Kaplan, I., Kwan, H. H., Allison, A. C. 1990; 124 (1): 43-49

    Abstract

    We have evaluated the effect of X irradiation on the mesenchymal tissue growth (blood capillaries and stromal cells) in an angiogenesis system in the mouse. This was accomplished by implanting a polyvinyl alcohol sponge disc in the subcutis of the thorax, and quantifying the extent of growth reduction of capillaries and stromal cells following graded doses of X rays. The sponge disc contained a centrally located pellet impregnated with 20 micrograms of epidermal growth factor and coated with a thin film of slow-releasing compound. Total growth of vessels and fibroblasts was determined by morphometric analysis of histologic sections. The incorporation of [3H]TdR was measured during a 24-h period. A dose-response relationship was observed when X irradiation was given on Day 11 after implantation, with the disc removed on Day 20. A single dose of 15 Gy reduced both the rate of incorporation of [3H]TdR and the total growth area. These and previous observations point to endothelial cells as important targets of ionizing radiation in the stroma, especially during the period of active proliferation of these cells, induced by growth factors.

    View details for Web of Science ID A1990EE91600007

    View details for PubMedID 1700450

  • The disc angiogenesis system. Laboratory investigation; a journal of technical methods and pathology Fajardo, L. F., Kowalski, J., Kwan, H. H., Prionas, S. D., Allison, A. C. 1988; 58 (6): 718-724

    Abstract

    A new system for the study of angiogenesis in vivo has been devised. It consists of a small disc of polyvinyl alcohol foam, covered on both flat sides by Millipore filters, leaving only the edge as the area for cell penetration into the disc. Angiogenic agonists or antagonists, as well as other substances to be studied, are placed in the center of the disc. The slow release of these substances is maintained by a film of ethylene-vinyl acetate co-polymer, or by the use of agarose. The disc is implanted subcutaneously in the host animal through a distant skin incision. In mice, the optimal times for examination of the discs are 7 to 12 days after implantation for discs containing angiogenic stimulants and 12 to 20 days for those without stimulants. After a period of growth is completed, the disc is removed, fixed, and embedded in paraffin or methacrylate. Medial plane sections, stained by a variety of methods, are used to observe and measure the growth of vessels and stroma into the disc. Whether stimulated or not, this growth is centripetal and can be easily quantitated by simple morphometric technics. This system has already been used in mice, to study the proliferation of vessels and fibroblasts into discs devoid of, or containing angiogenic stimulants (epidermal growth factor, acidic fibroblastic growth factor). We have also utilized the discs to demonstrate the inhibition of vessel growth by hyperthermia. Examples of these applications are presented. The disc angiogenesis system is easy to prepare, inexpensive, and well tolerated, at least by mice. Its simplicity and reproducibility make it suitable for a wide range of applications beyond those described here.

    View details for PubMedID 2454350

  • HYPERTHERMIA INHIBITS ANGIOGENESIS RADIATION RESEARCH Fajardo, L. F., Prionas, S. D., Kowalski, J., Kwan, H. H. 1988; 114 (2): 297-306

    Abstract

    Since in vitro studies have demonstrated that capillary endothelial cells are thermosensitive, experiments were performed to determine the (in vivo) heat sensitivity of blood capillaries and their endothelial cells. Angiogenesis discs were implanted subcutaneously in mice, and vascular growth was stimulated by slow release of epidermal growth factor placed in the center of each disc. After 5 days of growth the discs were subjected to radiofrequency-induced hyperthermia. Heat exposures were 41, 42, 43, and 44 degrees C for 30 min. Control discs were sham treated. Seven days after heating the discs were extracted and paraffin embedded. Centripetal (radial) vessel growth was measured in magnified medial planar sections. An inverse relationship was demonstrated between vessel growth and exposure temperature. The extent of the fibroblastic growth was also inversely proportional to temperature. Thus, at least in this system, the microvasculature shows dose-dependent damage by hyperthermia, consistent with preceding in vitro observations. This inhibition of angiogenesis may result from endothelial cell killing, interference with cell replication, inhibition of cell migration, or a combination of these mechanisms.

    View details for Web of Science ID A1988N486000010

    View details for PubMedID 2453896

  • VASCULAR-LESIONS FOLLOWING RADIATION PATHOLOGY ANNUAL Fajardo, L. F., BERTHRONG, M. 1988; 23: 297-330

    Abstract

    The special radiation sensitivity of the vascular system is mainly linked to that of endothelial cells, which are perhaps the most radiation-vulnerable elements of mesenchymal tissues. Within the vascular tree, radiation injures most often capillaries, sinusoids, and small arteries, in that order. Lesions of veins are observed less often, but in certain tissues the veins are regularly damaged (e.g., intestine) or are the most affected structures (i.e., liver). Large arteries do suffer the least; however, when significant damage does occur in an elastic artery (e.g., thrombosis or rupture), it tends to be clinically significant and even fatal. Although not always demonstrable in human tissues, radiation vasculopathy generally is dose and time dependent. Like other radiation-induced lesions, the morphology in the vessels is not specific, but it is characteristic enough to be often recognizable. Vascular injury, especially by therapeutic radiation is not just a morphologic marker. It is a mediator of tissue damage; perhaps the most consistent pathogenetic mechanism in delayed radiation injury.

    View details for Web of Science ID A1988AB14700010

    View details for PubMedID 3387138

  • SAFETY OF I-125 AND IR-192 IMPLANTS TO THE CANINE CAROTID-ARTERY - LONG-TERM RESULTS ACTA OTO-LARYNGOLOGICA Fee, W. E., Goffinet, D. R., Fajardo, L. F., GUTHANER, D., HANDEN, C. 1987; 103 (5-6): 514-518

    Abstract

    Thirty-nine healthy dogs underwent a simulated radical neck dissection followed by implantation of either 125Iodine (125I) or 192Iridium (192Ir) in various dose regimes randomized prospectively from 3,000 to 30,000 rad. Bilateral selective carotid angiography was performed immediately postoperatively and at 6, 12, 18, and 24 months. No significant effects occurred to the animals who received 15,000 rad 125I or 6,000 rad 192Ir. In the higher dosed animals the 125I-treated group fared better than the 192Ir-treated group, probably due to the lower dose rate delivery. Fewer and less serious complications occurred in the 125I-treated group, but this group developed more complications after one year than the Iridium group.

    View details for Web of Science ID A1987H681100028

    View details for PubMedID 3618180

  • VONWILLEBRAND-FACTOR LEVELS DO NOT PREDICT OR DIAGNOSE RADIATION PNEUMONITIS INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Fajardo, L. F., Donaldson, S. S., KELLY, N. I. 1986; 12 (1): 107-110

    Abstract

    In search for an index of endothelial injury that would provide an early diagnosis of radiation pneumonitis, we investigated the plasma levels of von Willebrand Factor (Factor VIII Related Antigen, FVIII:RAg) in 14 patients undergoing pulmonary irradiation. This study was based on observations indicating that damage to the endothelium-rich pulmonary parenchyma may produce alterations in the synthesis, storage or release of FVIII:RAg, detectable in plasma. There was no correlation between FVIII:RAg levels and radiation pneumonitis, radiation dose, volume of irradiated lung, tumor burden, or time-interval between exposure and sampling. The heterogeneity of the neoplasms and the inconstant effects of radiation in the tumor vasculature are among several variables that may explain this lack of correlation. The plasma levels of FVIII:RAg cannot be used to diagnose or predict radiation pneumonitis.

    View details for Web of Science ID A1986AYV1700017

    View details for PubMedID 3484736

  • Ionizing radiation and neoplasia. Monographs in pathology Fajardo, L. F. 1986: 97-125

    View details for PubMedID 3531819

  • SAFETY OF I-125 AND IR-192 IMPLANTS TO THE CANINE CAROTID-ARTERY - PRELIMINARY-REPORT LARYNGOSCOPE Fee, W. E., Goffinet, D. R., Fajardo, L. F., GUTHANER, D., HANDEN, C. 1985; 95 (3): 317-320

    Abstract

    Thirty-nine healthy dogs underwent a simulated radical neck dissection followed by implantation of either 125Iodine (125I) or 192Iridium (192Ir) in various dose regimes randomized prospectively from 3,000 to 30,000 rad. Bilateral selective carotid angiography was performed immediately postoperatively and at six months and one year. No significant effects occurred to the animals who received 15,000 rad 125I or 6,000 rad 192Ir. In the higher dosed animals the 125I treated group fared better than the 192Ir treated group, probably due to the lower dose rate delivery. All surviving animals will be maintained an additional year to determine the late effects of brachytherapy irradiation to the carotid artery.

    View details for Web of Science ID A1985ADK4500015

    View details for PubMedID 3974384

  • THERMAL SENSITIVITY OF ENDOTHELIAL-CELLS RADIATION RESEARCH Fajardo, L. F., SCHREIBER, A. B., KELLY, N. I., Hahn, G. M. 1985; 103 (2): 276-285

    Abstract

    Experimental work indicates that one of the mechanisms of tumor control by hyperthermia may be damage to blood vessels, resulting in decreased blood flow to the neoplasms. Among the various elements of the microvasculature, endothelial cells are the most important possible targets of thermal injury. Furthermore, neoplasms have a significantly higher proportion of proliferating endothelial cells than do normal tissues. Thus it is necessary to establish the thermal sensitivity of endothelial cells and to explore possible differences in response between resting and proliferating endothelium. We studied the in vitro thermal sensitivity of murine and human capillary endothelial cells compared to human fibroblasts by following cell survival and growth recovery. Nonstimulated endothelial cells are more sensitive than fibroblasts. Their sensitivity is dose dependent within the range of 42 to 45 degrees C/30 min. Stimulation to proliferate by endothelial cell growth factor (ECGF) renders these cells even more sensitive. Morphologic studies confirm these thermal effects in endothelial cells and fibroblasts. These findings support a direct effect of hyperthermia on endothelial cells, which appears to be more severe in proliferating cells. This may explain the reduced blood flow in heated tumors and may indicate a valuable therapeutic gain for hyperthermia.

    View details for Web of Science ID A1985ANY2300011

    View details for PubMedID 4023180

  • THERMAL SENSITIVITY TO SINGLE AND DOUBLE HEAT-TREATMENTS IN NORMAL CANINE LIVER CANCER RESEARCH Prionas, S. D., TAYLOR, M. A., Fajardo, L. F., KELLY, N. I., NELSEN, T. S., Hahn, G. M. 1985; 45 (10): 4791-4797

    Abstract

    The treatment of intrahepatic or perihepatic neoplasms by hyperthermia may be limited by the thermal sensitivity of normal liver tissue. To establish the temperature dependence of hepatic toxicity, eight canine liver lobes were exposed to a single 30-min dose of localized hyperthermia in the range of 43.0 degrees C-47.5 degrees C, induced by radiofrequency currents. Four additional liver lobes were conditioned with a pretreatment dose of 43.0 degrees C/30 min and challenged at either 44.5 degrees C/30 min or 47.5 degrees C/30 min, 4 h later. Temperature distributions were measured using implantable thermocouple sensors. Treated areas were sampled 28 days later, and liver damage was determined using histopathological criteria. Most treated sites showed only modest alterations. The parameters of tissue injury that correlated best with dose were: evidence of hepatocyte loss; focal fibrosis; and distortion of lobular architecture. Areas of necrosis were observed in several samples, but their presence or severity did not correlate with dose. Thermal damage to liver capsule, liver lobules, portal areas, and central veins did not exhibit monotonic dose-response relationships. The data do not demonstrate thermotolerance; in fact, they suggest, although do not prove, its absence. If thermotolerance did not develop, vascular effects might explain such a finding.

    View details for Web of Science ID A1985ARH6200014

    View details for PubMedID 4027968

  • CORRELATION OF THE DERMAL MICROVASCULATURE MORPHOLOGY WITH THE EPIDERMAL AND THE ENDOTHELIAL POPULATION-CHANGES PRODUCED BY SINGLE X-RAY FRACTIONS OF 1649-RAD, 2231-RAD AND 2619-RAD IN SWINE INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Archambeau, J. O., Ines, A., Fajardo, L. F. 1985; 11 (9): 1639-1646

    Abstract

    The role of the dermal microvasculature in the production of skin changes has not been specified. The healing moist reaction observed between 21 and 36 days following X ray exposures of 1649, 2231, and 2619 rad results from the loss and repopulation of the epidermal basal cells. The second breakdown occurring between 36 and 70 days results from the loss of endothelial cells in vessels of the papillary plexus. The epidermal population in swine skin decreases linearly to a nadir at 23 days and returns to control levels (and beyond) exponentially at 28-32 days. During this period, the endothelial cell density remains at control levels. At 28-36 days there is an abrupt decrease to 50% of control levels following administration of 1649 rad and a further decrease to 0 after 2231 and 2619 rad by 70 days. The qualitative morphology of the microvasculature remains unchanged until 32-36 days following irradiation. At that time there is increased endothelial cell pyknosis and loss of endothelial cells. A decrease in the vascular lumen cross-section profile density occurs by 43-49 days. This is accompanied by a progressive vascular dilatation. Interstitial edema becomes marked, with an inflammatory infiltrate of varying amount. Micro thrombi are found after 2619 rad, but are nearly absent after 1649 rad.

    View details for Web of Science ID A1985AQD0300008

    View details for PubMedID 4030432

  • Pathological effects of hyperthermia in normal tissues. Cancer research Fajardo, L. F. 1984; 44 (10): 4826s-4835s

    Abstract

    This is a brief review of the major pathological alterations produced by hyperthermia in normal tissues of humans and other mammals. Whole-body hyperthermia, spontaneous or artificially induced, can produce severe lesions that have been best described in humans: necropsies, of fatal cases of heatstroke or of individuals treated in the 1940s by hyperpyrexia, have demonstrated important lesions in the central nervous system, liver, kidney, heart, adrenal, testis, and bone marrow. All cases have shown hemorrhagic diathesis affecting many tissues, and in some the hemorrhages may have directly contributed to death. The information on the pathology of localized hyperthermia comes mainly from experimental studies in mammals. Pathology descriptions are available mainly for skin, mesenchymal tissues (skeletal muscle and adipose tissue), liver, small intestine, brain, kidney, urinary bladder, prostate, and cartilage. In several of these tissues, however, the morphological data are incomplete, and very few have sequential observations. Thus, the ultimate (delayed) result of the acute lesions of focal hyperthermia is unknown for most tissues. Clearly, more information is needed in order to define the range of safety for clinical hyperthermia.

    View details for PubMedID 6467235

  • ENHANCED PARASITIZATION OF PLATELETS BY PLASMODIUM-BERGHEI-YOELII TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE Perkash, A., KELLY, N. I., Fajardo, L. F. 1984; 78 (4): 451-455

    Abstract

    In previous studies plasmodia have been found by electron microscopy within human platelets naturally infected with Plasmodium vivax and within platelets of mice infected intraperitoneally with P. berghei. In both situations the number of parasitized platelets was low. An enhancement of platelet parasitization was attempted in order to study in greater detail the mechanisms and implications of such a phenomenon. Various in vitro incubation mixtures of normal mouse platelets and free merozoites of the 17X strain of P. berghei yoelii failed to produce any recognizable parasitization of platelets. In vivo, however, large numbers of invaded platelets were obtained by the use of massive intraperitoneal inocula of plasmodia (5 X 10(8) infected erythrocytes). By the 5th day of infection the proportion of parasitized platelets was 13.2 times higher in the animals receiving the large dose than in those receiving the regular passage inoculum (6 X 10(6) infected erythrocytes). Ultrastructural study of 266 intrathrombocytic parasites over eight days of infection failed to show schizogonic maturation beyond the trophozoite state.

    View details for Web of Science ID A1984TG66100006

    View details for PubMedID 6485052

  • PHARMACOKINETICS OF IN-111 BLEDTA IN MAN INVESTIGATIVE RADIOLOGY Sartoris, D. J., Goodwin, D. A., Meares, C. F., DERIEMER, L. H., Fajardo, L. F. 1984; 19 (3): 221-227

    Abstract

    111In-BLEDTA is a bleomycin-containing radiopharmaceutical that has proven useful as a tumor imaging agent. Whole blood distribution and pharmacokinetic parameters were studied in nine cancer patients, and the results compared with previously reported studies using 57Co-bleomycin. In eight patients studied by bolus intravenous injection, 111In-BLEDTA had a beta half-life (t1/2 beta) of 1.3 hours, a terminal-phase half-life (t1/2) of 11.7 hours, a volume of distribution (Vd gamma) of 57.5L/m2, a total body clearance rate (C1b) of 52.8 ml/min/m2, a renal clearance rate (C1r) of 23.3 ml/min/m2, and a 24-hour urinary excretion of 38.1% total administered dose. 111In-BLEDTA and 57Co-bleomycin have similar C1bs but differing Vds. Polymorphonuclear cell uptake of 111In-BLEDTA may explain its shorter t1/2 beta and t1/2, as well as its lower C1r and 24-hour urinary excretion. While the biologic characteristics of 111In-BLEDTA contribute to a greater background activity than is observed in scans with 57Co-bleomycin, its superior physical properties render it clinically more desirable as a tumor-imaging radiopharmaceutical.

    View details for Web of Science ID A1984SS78900012

    View details for PubMedID 6206021

  • RESPONSE OF SWINE SKIN MICROVASCULATURE TO ACUTE SINGLE EXPOSURES OF X-RAYS - QUANTIFICATION OF ENDOTHELIAL CHANGES RADIATION RESEARCH Archambeau, J. O., Ines, A., Fajardo, L. F. 1984; 98 (1): 37-51

    Abstract

    An acute single X-ray exposure of 2300 R produces in swine skin a moist reaction (ulceration) that appears at 17 days, heals by 32 days, and may break down again between 42 and 70 days. Initial studies quantified the epidermal population density changes during this 70-day period. This study was designed to quantify the density changes occurring in the endothelial cell population of the dermal microvasculature. While the basal population decreases to a nadir of 10% control by 24 days, the endothelial population remains at control levels. Beyond 24 days, the endothelial cell density decreases abruptly to 50% as the epidermal cell density returns to control levels and overshoots by 20% at 32 days. Subsequently, both populations decrease to zero by 57 days. Endothelial cell loss parallels a similar decrease in vascular lumen density. These findings indicate that the initial moist reaction results from a radiation-induced loss of epidermal cells, while the second reaction results from the loss of dermal microvasculature.

    View details for Web of Science ID A1984SM85800004

    View details for PubMedID 6718694

  • PROTECTION FROM RADIATION NEPHROPATHY BY WR-2721 RADIATION RESEARCH Donaldson, S. S., MOSKOWITZ, P. S., Evans, J. W., Fajardo, L. F. 1984; 97 (2): 414-423

    Abstract

    The efficacy of WR-2721 pretreatment against radiation injury to the growing kidney was evaluated in the weanling mouse. Immediately following unilateral nephrectomy, animals received intraperitoneal injections of saline or WR-2721 (220 mg/kg). Thirty minutes later both nonprotected (saline-treated) control animals and protected (WR-2721-treated) animals received 1000-rad single-fraction radiation to the remaining kidney. Other animals received WR-2721 immediately following unilateral nephrectomy but no radiation. Animals were sacrificed at 3 and 24 weeks. Nonirradiated animals treated with WR-2721 only showed normal compensatory renal growth, body growth, and renal function at 24 weeks. The nonprotected, irradiated animals exhibited renal growth inhibition without body growth inhibition, and renal functional abnormalities including elevation of serum BUN and reduction of glomerular filtration rate. Pretreatment with WR-2721 prior to 1000 rad prevented the renal growth inhibition and functional abnormalities seen in the nonprotected irradiated animals. Within the observation period there were no differences in renal morphology by light and electron microscopy between protected and nonprotected groups; only mild glomerular and tubular abnormalities compatible with radiation injury were seen. WR-2721 can modulate renal radiation injury; however, the growth and functional protection is not well correlated with specific histologic change. The dose reduction factor for WR-2721 renal growth protection is between 1.16 and 1.2. WR-2721 may have future clinical utility by increasing radiation tolerance of the kidney.

    View details for Web of Science ID A1984SD80900019

    View details for PubMedID 6320252

  • RADIATION-INDUCED HEART-DISEASE - AN UPDATE PROGRESS IN CARDIOVASCULAR DISEASES Stewart, J. R., Fajardo, L. F. 1984; 27 (3): 173-194

    View details for Web of Science ID A1984TS47900003

    View details for PubMedID 6387801

  • Thermal injury and thermotolerance in mesenchymal tissues. Frontiers of radiation therapy and oncology Fajardo, L. F., Meyer, J. L., Meshorer, A., PRIONAS, S., Martinez, A. A., Hahn, G. M. 1984; 18: 144-152

    View details for PubMedID 6706131

  • THE EFFECTS OF HYPERTHERMIA ON NORMAL MESENCHYMAL TISSUES - APPLICATION OF A HISTOLOGIC GRADING SYSTEM ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE Meshorer, A., Prionas, S. D., Fajardo, L. F., Meyer, J. L., Hahn, G. M., Martinez, A. A. 1983; 107 (6): 328-334

    Abstract

    The alterations produced by radiofrequency-induced hyperthermia of 42 to 48 degrees C for 30 minutes were studied in the subcutaneous adipose tissue and skeletal muscle of swine. Acute lesions (18 to 24 hours) included edema, hemorrhage, necrosis (predominantly of myocytes) and granulocytic exudate in fat or muscle. The most important chronic lesion (28 to 31 days) was fibrosis replacing either tissue. There was a histiolymphocytic exudate with foreign-body giant cells around large lipid vacuoles. Muscle necrosis persisted and there was variable myocyte regeneration. Several specimens showed deep necrosis and abscesses. A grading system was developed to quantitate independently acute and chronic damage in each tissue. Acute lesions were usually less severe and extensive than chronic ones, without obvious dose response. Chronic lesions showed clearly a dose response, which began at 43 degrees C and increased with temperature. The latter appear to be reliable indicators of hyperthermic damage in deep soft tissues.

    View details for Web of Science ID A1983QR22300014

    View details for PubMedID 6687797

  • THERMAL SENSITIVITY AND THERMOTOLERANCE IN NORMAL PORCINE TISSUES CANCER RESEARCH Martinez, A. A., Meshorer, A., Meyer, J. L., Hahn, G. M., Fajardo, L. F., Prionas, S. D. 1983; 43 (5): 2072-2075

    Abstract

    We have previously presented a histopathological grading scheme for thermal damage in normal porcine adipose and skeletal muscle tissues. Here we have used this scheme to assess the heat sensitivity of these tissues, and evaluate the protective benefit of thermotolerance as induced by a prior thermal exposure. Tissues were exposed to temperatures ranging from 40-50 degrees for 30 min. Half of all sites also received a thermal exposure of 41.0-43.0 degrees 4 hr earlier. Biopsies for histological evaluation were obtained at 18 to 24 hr ("acute") and at 28 to 31 days ("chronic") following treatment. Only mild acute injury was seen in the early samples, following either single or double heat exposures, at all temperature levels. Minimal chronic damage was also seen in the late samples following single exposures of 45 degrees or less. Higher single exposures caused important chronic lesions, the severity of which was dose dependent. Regions that had received the earlier conditioning thermal exposure showed a significant protection against the subsequent thermal exposure. In such regions, mean (chronic) pathology scores were reduced by 76 to 86% over the temperature range 45-48 degrees. The degree of acute damage failed to predict the degree of chronic damage. Overall, induction of thermotolerance provided an advantage of 2 degrees or more in normal tissue protection.

    View details for Web of Science ID A1983QN19500025

    View details for PubMedID 6831438

  • FAT NECROSIS OF THE BREAST SIMULATING RECURRENT CARCINOMA AFTER PRIMARY RADIOTHERAPY IN THE MANAGEMENT OF EARLY STAGE BREAST-CARCINOMA CANCER Clarke, D., Curtis, J. L., Martinez, A., Fajardo, L., Goffinet, D. 1983; 52 (3): 442-445

    Abstract

    Between March 1973 and December 1980, 76 patients with Stage I or II breast carcinoma were treated by biopsy and definitive radiation therapy at Stanford University Medical Center. There were 78 treated breasts since two patients had bilateral carcinomas at presentation. During a median follow-up period of 29 months, eight patients developed discrete masses in the treated breast. In four of these patients biopsied tissue revealed recurrent carcinoma yielding a local control rate of 95%. Four additional patients had lesions which were clinically indistinguishable from recurrent cancer. Biopsy specimens, however, revealed fat necrosis of the breast. The clinical and pathologic features of this entity are described. It is imperative that clinicians be aware of this treatment sequelae so that conservative diagnostic procedures may be used and breast deformity minimized. If postirradiation fat necrosis is considered, mastectomy for suspected persistent or recurrent disease may be avoided.

    View details for Web of Science ID A1983QZ18400009

    View details for PubMedID 6861083

  • DIFFERENTIAL RADIATION RESPONSE OF CULTURED ENDOTHELIAL-CELLS AND SMOOTH MYOCYTES ANALYTICAL AND QUANTITATIVE CYTOLOGY AND HISTOLOGY Johnson, L. K., LONGENECKER, J. P., Fajardo, L. F. 1982; 4 (3): 188-198

    Abstract

    In vivo observations have suggested that endothelial cells are the most radiosensitive elements of the vascular wall. To test whether this represents an intrinsic differential sensitivity, the response of bovine aortic endothelial cells and smooth myocytes was investigated in confluent cell cultures exposed to single doses of gamma radiation (250, 500, 1,000 or 2,000 rad). Both cell types showed a dose-dependent decrease in attachment efficiency when dissociated and replated at six hours after radiation. However, the attachment efficiency in both cell types was similar when a 72-hour postirradiation incubation period was used prior to dissociation of the cells. Growth inhibition was significantly greater (7- to 10-fold) in endothelial cells than in myocytes when examined four days after attachment. Confluent endothelial monolayers showed a dose-dependent, progressive cell loss during the 72-hour postirradiation period (70% after 1,000 rad); the myocyte cultures showed no radiation effect on the cell numbers. In spite of the reduction in number, the endothelial cells maintained the continuity of their monolayer by compensation with an increase in mean cell size. Endothelial cells developed multiple structural lesions, including an increase in the number and size of residual and lysosomal bodies, electron-lucent cytoplasmic defects, interruptions in the plasma membrane and irregular aggregation of chromatin, causing electron-lucent nuclei. These changes increased in severity with time and dose and were most pronounced 24 to 72 hours after 1,000 rad. No significant ultrastructural alterations were detected in myocytes four days after 2,000 rad.

    View details for Web of Science ID A1982PK37100004

    View details for PubMedID 7149484

  • SPLENIC INJURY CAUSED BY THERAPEUTIC IRRADIATION AMERICAN JOURNAL OF SURGICAL PATHOLOGY Dailey, M. O., Coleman, C. N., Fajardo, L. F. 1981; 5 (4): 325-331

    Abstract

    Splenic irradiation in the course of therapy for lymphoma can result in functional deficit, sometimes as severe as that caused by splenectomy, placing the patient at risk for fatal infection. We examined 33 spleens obtained at necropsy from patients irradiated for lymphomas (mainly Hodgkin's disease) and compared them with 18 nonirradiated spleens from similar patients. One to 8 years after a mean radiation dose of 3899 rads, fractionated over 5-6 weeks, most irradiated spleens were small (average weight 75 g) and had thick, wrinkled capsules, often with focal hemorrhage. There was collapse of the parenchyma, with close apposition of trabeculae and mild to severe diffuse fibrosis of the red pulp. Lymphocyte depletion was obvious in more than 50% of the specimens. The most consistent alteration was myointimal proliferation of arteries. Significant intimal thickening was seen only in the irradiated specimens. Similar myointimal changes were found in the veins of three cases. While none of these changes is specific, their combination appears to be characteristic of delayed radiation injury to the spleen.

    View details for Web of Science ID A1981LU97800002

    View details for PubMedID 7270781

  • RADIATION-INJURY IN SURGICAL PATHOLOGY .2. ALIMENTARY-TRACT AMERICAN JOURNAL OF SURGICAL PATHOLOGY BERTHRONG, M., Fajardo, L. F. 1981; 5 (2): 153-178

    View details for Web of Science ID A1981LG51100003

    View details for PubMedID 7013506

  • RADIATION-INJURY IN SURGICAL PATHOLOGY .3. SALIVARY-GLANDS, PANCREAS AND SKIN AMERICAN JOURNAL OF SURGICAL PATHOLOGY Fajardo, L. F., BERTHRONG, M. 1981; 5 (3): 279-296

    View details for Web of Science ID A1981LL61700008

    View details for PubMedID 7235121

  • INACCURACY IN AUTOMATED MEASUREMENT OF HEMATOCRIT AND CORPUSCULAR INDEXES IN THE PRESENCE OF SEVERE HYPERGLYCEMIA BLOOD Strauchen, J. A., ALSTON, W., Anderson, J., GUSTAFSON, Z., Fajardo, L. F. 1981; 57 (6): 1065-1067

    Abstract

    Because we recently observed two patients with severe diabetic hyperglycemia and spuriously elevated electronically determined hematocrit and mean corpuscular volume (MCV), we investigated the effect of hyperglycemia on two popular automated hematology systems, the Coulter S and Ortho ELT-8. Marked hyperglycemia (blood glucose 800--2000 mg/dl) caused consistent overestimation of the electronically determined MCV compared to that derived from a simultaneous spun microhematocrit. The resultant overestimation and underestimation, respectively, of the derived values for hematocrit and mean corpuscular hemoglobin concentration may be clinically misleading. The mechanism of MCV elevation in hyperglycemia appears to be swelling of hyperosmolar glucose "loaded" erythrocytes when diluted into "isotonic" counting medium. This effect is readily circumvented by determination of a spun microhematocrit.

    View details for Web of Science ID A1981LT01600011

    View details for PubMedID 6784789

  • PATHOGENESIS OF VENO-OCCLUSIVE LIVER-DISEASE AFTER RADIATION ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE Fajardo, L. F., Colby, T. V. 1980; 104 (11): 584-588

    Abstract

    Radiation-induced liver disease is characterized structurally by progressive fibrous obliteration of central veins (veno-occlusive disease [VOD]). The pathogenesis is unknown. Samples of liver from 11 patients with radiation-induced VOD were studied by light and electron microscopy for evidence of central vein thrombosis. The patients had received fractionated radiation with total doses of 1,850 to 4,050 rads, or single doses of 1,000 rads. In addition, six patients had received chemotherapy. Although usually undetectable by light microscopy, fibrin was found in all samples, sometimes in large amounts, within central veins, and also often in the adjacent sinusoids. One sample had a small platelet aggregate. In two patients, portal veins also showed occlusive lesions. We postulate that ionizing radiation injures preferentially the endothelial cells of central veins, which leads to focal deposition of fibrin. The resulting fibrin network is eventually replaced by collagen, causing fibrous occlusion. In several patients, this type of liver injury occurred at radiation doses conventionally considered safe even in the absence of chemotherapy.

    View details for Web of Science ID A1980KQ06200007

    View details for PubMedID 6893535

  • COMBINATION RADIATION-ADRIAMYCIN THERAPY - RENOPRIVAL GROWTH, FUNCTIONAL AND STRUCTURAL EFFECTS IN THE IMMATURE MOUSE INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Donaldson, S. S., MOSKOWITZ, P. S., CANTY, E. L., Fajardo, L. F. 1980; 6 (7): 851-859

    View details for Web of Science ID A1980KA92600010

    View details for PubMedID 7204121

  • ADRIAMYCIN NEPHROTOXICITY LABORATORY INVESTIGATION Fajardo, L. F., ELTRINGHAM, J. R., Stewart, J. R., Klauber, M. R. 1980; 43 (3): 242-253

    View details for Web of Science ID A1980KJ93800006

    View details for PubMedID 7401634

  • EFFECTS OF HYPERTHERMIA IN A MALIGNANT-TUMOR CANCER Fajardo, L. F., Egbert, B., Marmor, J., Hahn, G. M. 1980; 45 (3): 613-623

    Abstract

    The mechanisms of immediate and delayed tumor cell killing by hyperthermia were investigated in EMT-6 neoplasms implanted in BALB/cKa mice. Radiofrequency electromagnetic fields were used to achieve a curative local dose of 44 degrees C for 30 minutes. The tumors were sampled sequentially, during and after heat therapy, and studied by light and elecron microscopy. Assays for cell survival, including cell cultures, were performed at various times after completion of therapy. Focal cytoplasmic swelling, rupture of the plasma membrane and peripheral migration of heterochromatin were observed 5 minutes after initiation of therapy and led to cytoplasmic fragmentation by the end of the treatment period (30 minutes). Necrosis of most cells occurred 2--6 hours after the end of treatment. At 48 hours, there were no recognizable tumor cells. A scar replaced the tumor bed 14 days later. Viable (clonogenic) tumor cells were still 2% of control levels at the end of therapy and then progressively decreased to 0.0003% at 48 hours, confirming the morphologic observations and indicating that factors other than the direct effect of heat on tumor cells contributed to complete tumor eradication. Our findings, coupled with previous studies, suggest that the immediate heat induced necrosis in this tumor occurs through the mechanisms of physical changes in the plasma membrane. The delayed (post-therapy) cell death is likely due to modifications in the environment of the tumor bed.

    View details for Web of Science ID A1980JE80700030

    View details for PubMedID 7353209

  • POSTERIOR OCULAR ABNORMALITIES AFTER IRRADIATION FOR RETINOBLASTOMA - A HISTOPATHOLOGICAL STUDY BRITISH JOURNAL OF OPHTHALMOLOGY Egbert, P. R., Fajardo, L. F., Donaldson, S. S., MOAZED, K. 1980; 64 (9): 660-665

    Abstract

    Radiation-induced ocular lesions in the posterior eye and orbit were investigated in 33 surgical specimens of patients with retinoblastoma. The eyes were obtained from children 7 months to 6 years of age. Seventeen eyes were irradiated; 16 eyes had not received irradiation and served as controls. The majority of the irradiated eyes were treated with 6000 rads of external beam radiation. They were removed at a mean of 23 months after radiotherapy. All specimens were examined simultaneously by 2 observers without knowledge of treatment and analysed for the presence or absence of 15 lesions. The most consistent lesions in the irradiated eyes were abnormalities of the retinal vessels (11 of 17 eyes) and striking changes in the ciliary arteries (13 of 17 eyes). The retinal vessels showed thickening of the wall, often caused by deposition of fibrillary material, sometimes with fibrin deposits. The most consistent lesion was myointimal proliferation with narrowing of the ciliary arteries. Lesions of the central retinal artery were less common but occurred only in irradiated patients.

    View details for Web of Science ID A1980KL85500004

    View details for PubMedID 7426587

  • ROLE OF PLATELETS IN INFECTIONS .1. OBSERVATIONS IN HUMAN AND MURINE MALARIA ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE Fajardo, L. F. 1979; 103 (3): 131-134

    Abstract

    The interaction between platelets and microorganisms may be underestimated. Our in vivo studies support a direct role of thrombocytes in malarial infections. We have found intrathrombocytic parasites of Plasmodium vivax (in 10% of men naturally infected) and P berghei (in 53% of mice experimentally infected); these were both merozoites and trophozoites. Neither the mechanism of parasitization (whether by active penetration or by phagocytosis) nor the outcome of this phenomenon is known. However, structures suggestive of partially digested parasitic material were seen in platelets of almost 50% of the men and 75% of the mice. These findings suggest that other microoganisms (fungi, bacteria, and viruses) may also enter thrombocytes in vivo. If so, platelets could play important roles, either favorable or deleterious, in infections.

    View details for Web of Science ID A1979GM16400007

    View details for PubMedID 371580

  • RADIATION-INJURY IN SURGICAL PATHOLOGY .1. AMERICAN JOURNAL OF SURGICAL PATHOLOGY Fajardo, L. F., BERTHRONG, M. 1978; 2 (2): 159-199

    View details for Web of Science ID A1978FA64400005

    View details for PubMedID 350063

  • CANCER AND CORONARY-ARTERY DISEASE INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Stewart, J. R., Fajardo, L. F. 1978; 4 (9-10): 915-916

    View details for Web of Science ID A1978FS82100023

    View details for PubMedID 711562

  • RADIATION-INJURY IN MOUSE KIDNEY .1. SEQUENTIAL LIGHT MICROSCOPIC STUDY INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Glatstein, E., Fajardo, L. F., Brown, J. M. 1977; 2 (9-10): 933-943

    View details for Web of Science ID A1977EJ73300011

    View details for PubMedID 591410

  • OXALOSIS AND CHRONIC RENAL-FAILURE AFTER INTESTINAL-BYPASS ARCHIVES OF INTERNAL MEDICINE GELBART, D. R., BREWER, L. L., Fajardo, L. F., Weinstein, A. B. 1977; 137 (2): 239-243

    Abstract

    A 45-year-old man underwent a jejunoileal shunt procedure for obesity. Twenty months later he developed severe oxalosis and chronic renal failure, which required maintenance hemodialysis. The sequential observation of two biopsy specimens and the necropsy (over a span of 39 months) suggests that oxalate deposition caused tubular obstruction and destruction with subsequent atrophy of nephrons. This indicates that patients undergoing intestinal bypass are at risk for developing irreversible renal failure due to enteric hyperoxaluria.

    View details for Web of Science ID A1977CV43200015

    View details for PubMedID 836109

  • ALLOPURINOL-INDUCED INTERSTITIAL NEPHRITIS ANNALS OF INTERNAL MEDICINE GELBART, D. R., Weinstein, A. B., Fajardo, L. F. 1977; 86 (2): 196-198

    View details for Web of Science ID A1977CU89600016

    View details for PubMedID 835946

  • RADIATION-INDUCED CORONARY-ARTERY DISEASE CHEST Fajardo, L. F. 1977; 71 (5): 563-564

    View details for Web of Science ID A1977DE67900001

    View details for PubMedID 852333

  • GLOMERULAR AND JUXTA-GLOMERULAR LESIONS IN RADIATION NEPHROPATHY RADIATION RESEARCH Fajardo, L. F., Brown, J. M., Glatstein, E. 1976; 68 (1): 177-183

    View details for Web of Science ID A1976CH82900018

    View details for PubMedID 967972

  • RUPTURE OF MAJOR VESSELS AFTER RADIATION CANCER Fajardo, L. F., Lee, A. 1975; 36 (3): 904-913

    Abstract

    Rupture of irradiated large vessels is an uncommon complication which tends to occur in carotid, aorta, and femoral arteries, in decreasing order of incidence. It particularly affects men subjected to surgery and radiotherapy for epidermoid carcinomas in oropharynx, esophagus, or genitalia. Contrary to some opinion, radiation is not the most significant cause; this "spontaneous" arterial rupture can occur without radiation. The perforation is not associated with tumor invasion of arterial wall, as has been claimed. Surgical complications, especially necrosis of skin flaps, infection, and fistulas are most important etiologically. Only 2 of the 11 instances that we describe appear to have been caused mainly by radiation. The perforation is usually fatal, but several patients, including 3 of our series (2 carotid, 1 femoral), have been saved by hospital personnel aware of this complication. To prevent it, prolonged exposure or infection of arteries, whether irradiated or not, should be avoided.

    View details for Web of Science ID A1975AR81400010

    View details for PubMedID 1182677

  • EVALUATION OF CRYOSURGERY FOR BASAL-CELL CARCINOMA PLASTIC AND RECONSTRUCTIVE SURGERY VISTNES, L. M., Harris, D. R., Fajardo, L. F. 1975; 55 (1): 71-75

    Abstract

    Fifteen histologically proven basal cell carcinomas were treated by conventional cryosurgery. Three to 6 months following healing, the entire treated area was excised and serially sectioned. There was clinical and microscopic evidence of residual tumor in two of the 15 cases and microscopic evidence of recurrence in one additional patient (20 percent recurrence).

    View details for Web of Science ID A1975V479500011

    View details for PubMedID 1114181

  • PLATELET MORPHOLOGY AFTER ASPIRIN AMERICAN JOURNAL OF CLINICAL PATHOLOGY Fajardo, L. F. 1975; 63 (4): 554-558

    Abstract

    Previous studies have revealed morphologic platelet abnormalities, particularly inclusions, in patients who have acute malarial infections. To determine the possible role of aspirin (ASA) in the etiology of these abnormalities, the thrombocytes of 14 normal men were examined before and after ingestion of 2 Gm. of ASA. A significant decrease in platelet size was noticed after ASA: however, no ultrastructural alteration of these circulating platelets was found, although functional impairment was manifested in vivo (bleeding time) and in vitro (aggregation). It is concluded that inclusions and other morphologic abnormalities in thrombocytes of malaria patients are not caused by aspirin ingestion.

    View details for Web of Science ID A1975W145100013

    View details for PubMedID 1119446

  • ADRIAMYCIN CARDIOMYOPATHY - ENHANCED CARDIAC DAMAGE IN RABBITS WITH COMBINED DRUG AND CARDIAC IRRADIATION RADIOLOGY ELTRINGHAM, J. R., Fajardo, L. F., Stewart, J. R. 1975; 115 (2): 471-472

    Abstract

    Rabbits received either (a) no treatment; (b) a single radiation dose; (c) protracted low-dose Adriamycin; (d) combined cardiac irradiation and low-dose Adriamycin; or (e) protracted high-dose Adriamycin. More severe myocardial lesions (similar to those in high-dose Adriamycin groups) developed in rabbits receiving combined treatment. Pericardial effusions and fibrosis were more common in the combined treatment group.

    View details for Web of Science ID A1975AA13300042

    View details for PubMedID 806934

  • ALPHA-1-ANTITRYPSIN DEFICIENCY - HEREDITARY ENIGMA AMERICAN JOURNAL OF CLINICAL PATHOLOGY Williams, W. D., Fajardo, L. F. 1974; 61 (3): 311-320

    View details for Web of Science ID A1974S422700001

    View details for PubMedID 4131010

  • Extra-adrenal pheochromocytoma causing renal artery stenosis. Relationship to hypertension and renin levels. Urology Freiha, F. S., KAVANEY, P. B., Cunningham, J. J., Fajardo, L. F., Castellino, R. A. 1973; 2 (3): 303-307

    View details for PubMedID 4747670

  • CARDIAC MURAL THROMBI CAUSED BY RADIATION RADIATION RESEARCH Fajardo, L. F., Brown, J. M. 1973; 55 (2): 387-389

    View details for Web of Science ID A1973Q515800016

    View details for PubMedID 4722692

  • FAILURE OF TOPICAL AMPHOTERICIN-B IN CRYPTOCOCCOSIS ANNALS OF INTERNAL MEDICINE Fajardo, L. F. 1973; 78 (5): 777-778

    View details for Web of Science ID A1973P560800026

    View details for PubMedID 4576207

  • TECHNIQUE FOR PERCUTANEOUS NEEDLE BIOPSY OF BONE AND MARROW CALIFORNIA MEDICINE Fajardo, L. F., SARASTI, H. 1972; 117 (2): 21-?

    View details for Web of Science ID A1972N303000005

    View details for PubMedID 5052052

  • PRIMARY CUTANEOUS CRYPTOCOCCOSIS - REVIEW AND MORPHOLOGIC STUDY AMERICAN JOURNAL OF CLINICAL PATHOLOGY Noble, R. C., Fajardo, L. F. 1972; 57 (1): 13-?

    View details for Web of Science ID A1972L375700002

    View details for PubMedID 4332932

  • CORONARY-ARTERY DISEASE AFTER RADIATION NEW ENGLAND JOURNAL OF MEDICINE Fajardo, L. F., Stewart, J. R. 1972; 286 (23): 1265-?

    View details for Web of Science ID A1972M629600012

    View details for PubMedID 5022894

  • CHARACTERISTICS OF A SERIALLY TRANSPLANTED MOUSE MAMMARY TUMOR AND ITS TISSUE-CULTURE-ADAPTED DERIVATIVE JOURNAL OF THE NATIONAL CANCER INSTITUTE ROCKWELL, S. C., KALLMAN, R. F., Fajardo, L. F. 1972; 49 (3): 735-?

    View details for Web of Science ID A1972N666100014

    View details for PubMedID 4647494

  • EOSINOPHILIA TERMINATING IN MYELOBLASTOMA AMERICAN JOURNAL OF MEDICINE Gershwin, M. E., GURWITH, M., Kosek, J. C., Fajardo, L. F. 1972; 53 (3): 348-?

    View details for Web of Science ID A1972N459100012

    View details for PubMedID 5054727

  • LARGE PLATELETS NEW ENGLAND JOURNAL OF MEDICINE Fajardo, L. F. 1971; 284 (12): 671-?

    View details for Web of Science ID A1971I814500012

    View details for PubMedID 5545611

  • CAPILLARY INJURY PRECEDING RADIATION-INDUCED MYOCARDIAL FIBROSIS RADIOLOGY Fajardo, L. F., Stewart, J. R. 1971; 101 (2): 429-?

    View details for Web of Science ID A1971K404700033

    View details for PubMedID 5114783

  • RADIATION-INDUCED HEART DISEASE- CLINICAL AD EXPERIMENTAL ASPECTS RADIOLOGIC CLINICS OF NORTH AMERICA Stewart, J. R., Fajardo, L. F. 1971; 9 (3): 511-?

    View details for Web of Science ID A1971L033200010

    View details for PubMedID 5001977

  • DOSE RESPONSE IN HUMAN AND EXPERIMENTAL RADIATION-INDUCED HEART DISEASE - APPLICATION OF NOMINAL STANDARD DOSE (NSD) CONCEPT RADIOLOGY Stewart, J. R., Fajardo, L. F. 1971; 99 (2): 403-?

    View details for Web of Science ID A1971I949000029

    View details for PubMedID 5553580

  • PLATELET ENLARGEMENT IN MALARIA MILITARY MEDICINE Fajardo, L. F., Rao, S. 1971; 136 (5): 463-?

    View details for Web of Science ID A1971J274000008

    View details for PubMedID 5005443

  • Experimental radiation-induced heart disease. I. Light microscopic studies. American journal of pathology Fajardo, L. F., Stewart, J. R. 1970; 59 (2): 299-316

    View details for PubMedID 5443637

  • SURGERY VS ELECTROSURGERY FOR RHINOPHYMA ARCHIVES OF OTOLARYNGOLOGY LINEHAN, J. W., Goode, R. L., Fajardo, L. F. 1970; 91 (5): 444-?

    View details for Web of Science ID A1970G008800009

    View details for PubMedID 4245633

  • CARDIOVASCULAR RADIATION SYNDROME NEW ENGLAND JOURNAL OF MEDICINE Fajardo, L. F., Stewart, J. R. 1970; 283 (7): 374-?

    View details for Web of Science ID A1970H003600016

    View details for PubMedID 4988599

  • METASTATIC BASAL CELL CARCINOMA - A REVIEW ARCHIVES OF PATHOLOGY WERMUTH, B. M., Fajardo, L. F. 1970; 90 (5): 458-?

    View details for Web of Science ID A1970H711700010

    View details for PubMedID 4920291

  • LIGHT AND ELECTRON MICROSCOPIC OBSERVATIONS ON GRANULOMATOUS ORCHITIS INVESTIGATIVE UROLOGY Fajardo, L. F., DUEKER, G. E., Kosek, J. C. 1968; 6 (2): 158-?

    View details for Web of Science ID A1968B842100008

    View details for PubMedID 5675378

  • MORPHOLOGY OF RADIATION-INDUCED HEART DISEASE ARCHIVES OF PATHOLOGY Fajardo, L. F., Stewart, J. R., COHN, K. E. 1968; 86 (5): 512-?

    View details for Web of Science ID A1968B996400007

    View details for PubMedID 5681435

  • HEART DISEASE FOLLOWING RADIATION MEDICINE COHN, K. E., Stewart, J. R., Fajardo, L. F., Hancock, E. W. 1967; 46 (3): 281-?

    View details for Web of Science ID A19679439700003

    View details for PubMedID 6026629

  • DISTRIBUTION OF BLOOD ANTIGENS A B AND D IN POPULATION OF BOGOTA (ANALYSIS OF 30000 SAMPLES) AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY Fajardo, L. F., Lavalle, Z. N. 1966; 24 (2): 257-?

    View details for Web of Science ID A19667799300014

    View details for PubMedID 5938204

  • [IMMUNOLOGIC DETERMINATION OF CLORIONIC GONADOTROPINS (AS A METHOD OF DIAGNOSING PREGNANCY)]. Revista de la Facultad de Medicina, Universidad Nacional de Colombia Sanchez, A. S., Fajardo, L. F. 1964; 32: 19-25

    View details for PubMedID 14260345

  • PREGNANCY AND AC-GLOBULIN DEFICIENCY - REPORT OF A CASE AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Fajardo, L. F., SILVERT, D. 1957; 74 (4): 909-914

    View details for Web of Science ID A1957WJ78400017

    View details for PubMedID 13458292

Conference Proceedings


  • RADIATION-INJURY TO THE HEART Stewart, J. R., Fajardo, L. F., Gillette, S. M., Constine, L. S. ELSEVIER SCIENCE INC. 1995: 1205-1211

    Abstract

    For the RTOG Consensus Conference on Late Effects of Cancer Treatment we summarize the clinical manifestations of cardiac complications appearing months to years following incidental irradiation of the heart during treatment of thoracic neoplasms. The most common effects present as pericardial disease, however, it is becoming more clear that precocious or accelerated coronary artery disease is an important late effect, especially in patients treated with radiation before the age of 21 years. To the extent it is known, the pathophysiology of the various syndromes is described and the extensive literature on dose, volume, and fractionation factors is reviewed. Based upon our current understanding of late cardiac effects, a clinical grading system has been developed and is published elsewhere in this issue.

    View details for Web of Science ID A1995QU29500012

    View details for PubMedID 7713783

  • HEPATIC TOXICITY RESULTING FROM CANCER-TREATMENT Lawrence, T. S., Robertson, J. M., Anscher, M. S., Jirtle, R. L., Ensminger, W. D., Fajardo, L. F. ELSEVIER SCIENCE INC. 1995: 1237-1248

    Abstract

    Radiation-induced liver disease (RILD), often called radiation hepatitis, is a syndrome characterized by the development of anicteric ascites approximately 2 weeks to 4 months after hepatic irradiation. There has been a renewed interest in hepatic irradiation because of two significant advances in cancer treatment: three dimensional radiation therapy treatment planning and bone marrow transplantation using total body irradiation. RILD resulting from liver radiation can usually be distinguished clinically from that resulting from the preparative regime associated with bone marrow transplantation. However, both syndromes demonstrate the same pathological lesion: veno-occlusive disease. Recent evidence suggests that elevated transforming growth factor beta levels may play a role in the development of veno-occlusive disease. Three dimensional treatment planning offers the potential to determine the radiation dose and volume dependence of RILD, permitting the safe delivery of high doses of radiation to parts of the liver. The chief therapy for RILD is diuretics, although some advocate steroids for severe cases. The characteristics of RILD permit the development of a grading system modeled after the NCI Acute Common Toxicity Criteria, which incorporates standard criteria of hepatic dysfunction.

    View details for Web of Science ID A1995QU29500014

    View details for PubMedID 7713785

  • EFFECTS OF IONIZING-RADIATION ON LYMPH-NODES - A REVIEW Fajardo, L. F. KARGER. 1994: 37-45

    View details for Web of Science ID A1994BB35T00004

    View details for PubMedID 7982602

  • LYMPH-NODES AND CANCER - A REVIEW Fajardo, L. F. KARGER. 1994: 1-10

    View details for Web of Science ID A1994BB35T00001

    View details for PubMedID 7982587

  • THE UNIQUE PHYSIOLOGY OF ENDOTHELIAL-CELLS AND ITS IMPLICATIONS IN RADIOBIOLOGY Fajardo, L. F. KARGER. 1989: 96-112

    View details for Web of Science ID A1989BP94U00007

    View details for PubMedID 2697671

  • MORPHOLOGIC PATTERNS OF RADIATION-INJURY Fajardo, L. F. KARGER. 1989: 75-84

    View details for Web of Science ID A1989BP94U00005

    View details for PubMedID 2697669

  • CEREBRAL MALARIA IN A VIRULENT RODENT PLASMODIAL INFECTION Yoeli, M., MOST, H., Hargreaves, B., Fajardo, L. ROYAL SOC TROPICAL MEDICINE. 1975: 4-5

    View details for Web of Science ID A1975W232600009

    View details for PubMedID 1096377

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