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Biomedical subjects

L F Fajardo

Publications and source records attributed to L F Fajardo.

At least 55 records · Page 3Linked to original sources
PubMed1985

Thermal sensitivity of endothelial cells.

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.

Animals↗
PubMed1985

Thermal sensitivity to single and double heat treatments in normal canine liver.

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.

Animals↗
PubMed1984

Enhanced parasitization of platelets by Plasmodium berghei yoelii.

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.

Animals↗
PubMed1984

Protection from radiation nephropathy by WR-2721.

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.

Amifostine↗
PubMed1984

Pathological effects of hyperthermia in normal tissues.

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.

Adrenal Glands↗
PubMed1984

Response of swine skin microvasculature to acute single exposures of X rays: quantification of endothelial changes.

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.

Animals↗
PubMed1983

Diet and gastric cancer: nutrition survey in a high-risk area.

A nutrition survey was done in four Colombian villages situated in the rural area of Nariño, previously identified as exhibiting different levels of risk for gastric cancer and its precursor lesions. The survey was based on personal visits by trained interviewers to a random sample of families in each village. The major findings of the survey reflected a higher consumption of fava beans in villages with high indices of gastric cancer risk and a higher consumption of fresh fruits and vegetables in villages where such indices were lower. Excessive salt intake and lower potassium intake in villages with a high risk of gastric cancer were suggested, but further work is required to test this preliminary observation. A generally low intake of animal proteins and a high intake of cereals in Nariño did not discriminate between villages at different levels of risk to gastric cancer and its precursors.

Adolescent↗
PubMed1983

The effects of hyperthermia on normal mesenchymal tissues. Application of a histologic grading system.

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.

Adipose Tissue↗
PubMed1983

Thermal sensitivity and thermotolerance in normal porcine tissues.

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.

Adipose Tissue↗
PubMed1982

Radiation injury of the normal and neoplastic prostate.

Tissue samples from 40 patients with prostatic adenocarcinoma treated by radiation therapy were evaluated simultaneously by three observers to establish criteria for distinguishing residual tumor from radiation-induced atypia. Sections from 10 patients irradiated for nonprostatic pelvic neoplasms served as controls in addition to pretreatment biopsies from the determinate group. Patients had been treated by external x-irradiation, the majority receiving 6200-7400 rad to the prostate and pelvis over 7 to 8 weeks. Positive (tumor) biopsy incidence in the determinate group was 80% at 18 months, 40% at 36 months, and 43% in later samples. The following features were characteristic of radiation injury in the prostate: decreased ratio of the number of tumor glands to stroma, atrophy and squamous-like metaplasia of non-neoplastic glands with or without atypia, stromal fibrosis, arterial lumenal narrowing due to myointimal proliferation, foam cells within vessel walls, and fibrosis and atrophy of seminal vesicles. Criteria not useful for diagnosing radiation injury included architectural pattern or differentiation of tumor, cytologic features of tumor cells, inflammatory infiltrate, and ratio of normal glands to stroma. Ionizing radiation produced characteristic lesions in neoplastic and non-neoplastic prostatic glands, stroma, and blood vessels, and the sum of these changes was a reliable indicator of prior radiotherapy. An understanding of the morphologic effects of radiation injury of the prostate allowed distinction between residual prostatic adenocarcinoma and radiation-induced atypia of non-neoplastic glands.

Adenocarcinoma↗
PubMed1982

Differential radiation response of cultured endothelial cells and smooth myocytes.

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.

Animals↗
PubMed1981

Splenic injury caused by therapeutic irradiation.

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.

Adult↗
PubMed1981

Inaccuracy in automated measurement of hematocrit and corpuscular indices in the presence of severe hyperglycemia.

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.

Autoanalysis↗
PubMed1980

Effects of hyperthermia in a malignant tumor.

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.

Animals↗