Effect of various microbial preparations on P-388 mouse lymphocytic leukemia.

Four bacteria-derived immunopotentiators were tested for their protective effect on a P-388 mouse lymphocytic leukemia model. The microbial test products were prepared from the following bacterial strains: ATCC 35983 Staphylococcus epidermidis isolated from a patient with IV catheter; ATCC 31874, a patented strain listed as Staphylococcus epidermidis isolated from the urine of a cancer patient; ATCC 25615 Staphylococcus hominis obtained from a child with lymphocytic leukemia, and ATCC 25614 Staphylococcus warneri, an isolate from a patient with adenocarcinoma of the breast. A limited degree of protection and prolongation in survival time was observed in the animal group treated with the bacterial strain ATCC 31874.


[Anthropometric and physiological characteristics of Puerto Rican cyclists].

This study was conducted to describe various anthropometric, body composition, cardiorespiratory, metabolic and neuromuscular characteristics of 31 athletes (F = 5, M = 26) members of the Puertorrican Cycling Federation's national pre-selection. The athletes were divided into four categories according to their sex and age. The mean and standard deviation of all the variables in each category was computed. An Analysis of Covariance was conducted to determine significant differences between the mean's of the four categories. Male cyclists showed superior results compared to female cyclists in all the variables studied except body mass, ectomorphy, VO2 max, max HR, max power (W), and neuromuscular function in which they showed no statistical differences. The anthropometric, body composition, max power (W) and cardiorespiratory characteristics of our cyclists compared with those reported for international cyclists. The groups means for push ups, sit ups and flexibility were below the excellent classification when compared to the general population's health related physical fitness norms.


Ethylcellulose as a carrier for controlled-release acetaminophen tablets.

In this study ethylcellulose was evaluated as a carrier for preparation of prolonged release acetaminophen tablets. Solid dispersions containing three levels of ethylcellulose and acetaminophen (1:3; 1:1; 3:1) were prepared by the solvent method. Also physical mixtures at the same level of ethylcellulose and acetaminophen were prepared. Systems composed of solid dispersion or physical mixture containing the equivalent weight of 50 mg acetaminophen, Emcompress as diluent and 1% magnesium stearate as lubricant were compressed into tablets and tested for dissolution. The dissolution data showed that the drug release decreased as the level of ethylcellulose increased in the solid dispersion formulations. The drug release from tablets prepared with solid dispersion followed the diffusion controlled model for inert porous matrix, while the drug release from tablets prepared with physical mixture followed the first-order kinetic model.


Psychosocial problems of deinstitutionalized VA psychiatric patients in Puerto Rico.

As a result of public law 99-166 the Department of Veterans Affairs Medical Center in San Juan (DVAMC), Puerto Rico engaged in a planned de-institutionalization of psychiatric veteran patients who had been treated in two contracted psychiatric hospitals in the community. This research seeks to determine whether they were receiving treatment after the deinstitutionalization effort was completed, the types of psychosocial problems they were facing and the resources utilized to cope with them. The authors found that the veterans were receiving treatment for their psychosocial problems, they relied to a great extent on DVAMC for services and that the psychosocial problems of those veterans over age 55 were less and differed from those under age 55.


Microdosimetry of diagnostic X rays: applications of the variance-covariance method.

Microdosimetric measurements in beams of diagnostic X rays (between 30 and 125 kV) have been performed. In these pulsed radiation fields, microdosimetric measurements are possible only by application of the variance-covariance technique. The dose mean lineal energy, yD, is determined for various simulated diameters, at different depths in the absorber, and at different points within the pulse intervals. From the measured temporal dependences one can also obtain values of yD for different X-ray pulse generators. The results demonstrate the potential of the variance-covariance method for a diversity of microdosimetric measurements in radiation protection and in the quality control of radiation beams.


Stopping power and the concept of effective ion charge at low energies.

A new formalism for the calculation of the ion-matter interaction phenomenon was developed by incorporating the atomic electron shell structure. This formalism allows for discrimination among the electrons of the target atoms according to their average positions with respect to the shell structure of the projectile ion. By doing so, we are able to show a strong dependence of the ion energy loss on its electron shell distribution. Thus a detailed quantum mechanical description of the moving ion is necessary to predict its precise trajectory and energy loss inside matter. The concept of an "effective charge" in the context of the electron stopping power formalism is emphasized and extended.


A spatially restricted linear energy transfer equation.

An analytical expression is developed for calculating the average energy deposited by an ion in a volume with dimensions less than the range of the secondary electrons produced. The expression is obtained by including two additional terms in an energy-restricted linear-energy-transfer equation. The usual energy-restricted expression accounts for energy deposited in the volume by energy transfers less than a certain cutoff value. The modified expression, due to the two additional terms, also accounts for energy deposited in the volume which results from energy transfers greater than the cutoff value. The additional terms therefore convert the energy-restricted equation to a distance- or spatially restricted equation. The method is used to obtain radial dose profile information on ion tracks and to calculate the energy deposited by an ion randomly incident upon spherical and hemispherical target sites. Results are in close agreement with more complex methods reported previously for ions with energies from 0.25 to 1000 MeV/amu in volumes of water vapor with dimensions from 1 nm to 10 microns. There are no fitted parameters in this general approach, and all the necessary input data are readily available.


Analysis of DNA damage at the dinucleoside monophosphate level: application to the formamido lesion.

The dinucleoside monophosphates d(TpG), d(TpC), and d(TpT) were X-irradiated in oxygenated solution. In each case the modification of the dinucleoside in which the thymine base is degraded to a formamido remnant was observed as a principal product. The hydrolysis of the phosphoester bond of formamido-modified dinucleosides is much slower than that of the corresponding unmodified dinucleosides. This effect is also observable in the hydrolysis of irradiated DNA, where hydrolysis by nuclease P1 (plus acid phosphatase) generates the modified dinucleosides d(TFpN), TF being the modified thymidine. The total yield of the formamido lesion in all its forms, d(TFpN), exceeds the yield of any other base modification.


Lipid peroxide levels in a murine adenocarcinoma exposed to hyperthermia: the role of glutathione depletion.

Increased lipid peroxide levels were obtained 1 h after a 60-min 43 degrees C hyperthermia treatment of a solid murine C3H mammary adenocarcinoma, grown subcutaneously in the hind paws of mice. Previous work from our group revealed that this heat treatment depletes the intracellular glutathione (GSH) content in this tumor. To investigate GSH depletion as one tentative mechanism behind the increased lipid peroxide levels obtained, we also measured the formation of lipid peroxidation products after extensive DL-buthionine-S,R-sulfoximine (BSO)-induced GSH depletion. The lipid peroxide effect provoked by BSO was less than that of the 60-min hyperthermia treatment. We therefore propose that the increased lipid peroxide levels induced by heat treatment do not correlate primarily with the observed decrease in GSH levels. Furthermore, in thermotolerance-induced tumors, lipid peroxide levels after a second heat treatment were observed to increase concomitantly with the cessation of thermotolerance. Lipid peroxide levels were also studied in liver, lung, and heart. Following BSO treatments, and up to 2-fold increase was observed in these organs in non-tumor-bearing mice. It was also observed that the intrinsic lipid peroxide levels in these organs from tumor-bearing mice were approximately 1.5- to 4-fold higher in comparison with non-tumor-bearing mice, thus indicating a systemic effect of the tumor implant.


Rat embryo cells immortalized with transfected oncogenes are transformed by gamma irradiation.

Cesium-137 gamma rays were used to transform rat embryo cells (REC) which were first transfected with activated c-myc or c-Ha-ras oncogenes to produce immortal cell lines (REC:myc and REC:ras). When exposed to 6 Gy of 137Cs gamma rays, some cells became morphologically transformed with focus formation frequencies of approximately 3 x 10(-4) for REC:myc and approximately 1 x 10(-4) for REC:ras, respectively. Cells isolated from foci of gamma-ray-transformed REC:myc (REC:myc:gamma) formed anchorage-independent colonies and were tumorigenic in nude mice, but foci from gamma-ray-transformed REC:ras (REC:ras:gamma) did not exhibit either of these criteria of transformation. Similar to the results with gamma irradiation, we observed a sequence-dependent phenomenon when myc and ras were transfected into REC, one at a time. REC immortalized by ras transfection were not converted to a tumorigenic phenotype by secondary transfection with myc, but REC transfected with myc were very susceptible to transformation by subsequent ras transfection. This suggests that myc-immortalized cells are more permissive to transformation via secondary treatments. In sequentially transfected REC, myc expression was high whether it was transfected first or second, whereas ras expression was highest when the ras gene was transfected secondarily into myc-containing REC. Molecular analysis of REC:ras:gamma transformants showed no alterations in structure of the transfected ras or of the endogenous ras, myc, p53, or fos genes. The expression of ras and p53 was increased in some isolates of REC:ras:gamma, but myc and fos expression were not affected. Similarly, REC:myc:gamma transformants did not demonstrate rearrangement or amplification of the transfected or the endogenous myc genes, or of the potentially cooperating Ha-, Ki-, or N-ras genes. Northern hybridization analysis revealed increased expression of N-ras in two isolates, REC:myc:gamma 33 and gamma 41, but no alterations in the expression of myc, raf, Ha-ras, or Ki-ras genes in any REC:myc transformant. DNA from several transformed REC:myc:gamma cell lines induced focus formation in recipient C3H 10T1/2 and NIH 3T3 cells. The NIH 3T3 foci tested positive when hybridized to a probe for rat repetitive DNA. A detailed analysis of the NIH 3T3 transformants generated from REC:myc:gamma 33 and gamma 41 DNA failed to detect Ha-ras, Ki-ras, raf, neu, trk, abl, fms, or src oncogenes of rat origin.(ABSTRACT TRUNCATED AT 400 WORDS)


Repeated inhalation exposure of rats to aerosols of 144CeO2. I. Lung, liver, and skeletal dosimetry.

To develop a better understanding of the influence of cumulative radiation dose and dose rate to the lungs on the biological responses to inhaled radionuclides, several studies are in progress at this institute in which laboratory animals have been exposed once or repeatedly to aerosols of insoluble particles containing 144Ce or 239Pu. In the study reported here, F344 rats were exposed repeatedly to aerosols of 144CeO2 beginning at 94 days of age to reestablish desired lung burdens of 1.9, 9.2, 46, or 230 kBq of 144Ce every 60 days for 1 year (seven exposures). Other 94-day-old rats were exposed once to achieve similar desired initial lung burdens of 144Ce. Older rats were exposed once to achieve desired initial lung burdens of 46 or 230 kBq when 500 days of age, the age of the repeatedly exposed rats when exposed for the last time. Control rats were either unexposed, sham-exposed once or repeatedly, or exposed once or repeatedly to stable CeO2. Approximately equal numbers of male and female rats were used. The cumulative beta-radiation doses to the lungs, liver, and skeleton of rats exposed repeatedly were similar to those of rats with similar total lung burdens of 144Ce from a single inhalation exposure. The average beta-radiation dose rate to the lungs of the rats exposed repeatedly was about one-fifth of that in rats with similar total lung burdens after a single exposure.


Repeated inhalation exposure of rats to aerosols of 144CeO2. II. Effects on survival and lung, liver, and skeletal neoplasms.

Groups of 94-day-old F344/Crl rats were exposed repeatedly to aerosols of 144CeO2 to reestablish desired lung burdens of 1.9, 9.2, 46, or 230 kBq of 144Ce every 60 days for 1 year (seven exposures). Other 94-day-old rats were exposed once to achieve similar desired initial lung burdens of 144Ce. Older rats were exposed once to achieve desired initial lung burdens of 46 or 230 kBq when 500 days of age, the same age at which rats had the last of the repeated exposures. Control rats were either unexposed, sham-exposed once or repeatedly, or exposed once or repeatedly to stable CeO2. Approximately equal numbers of male and female rats were used. The median survival time and cumulative percentage survival curves were significantly decreased only in male and female rats exposed repeatedly to reestablish a 230-kBq lung burden and among the 94-day-old male rats exposed once to achieve a 230-kBq lung burden of 144Ce. The crude incidences of primary lung cancers (well described by a single Weibull distribution function), time to death with lung tumors, and risk of lung cancer per unit of beta-radiation dose to the lungs were correlated with the cumulative beta-radiation dose rather than the rate at which the dose was accumulated. A linear function, 70 (+/- 7.3) + -0.15 (+/- 0.056) x dose (+/- SD), adequately described the excess numbers of rats with lung cancers over a beta-radiation dose range to the lungs of 6.8 to 250 Gy for two groups of rats with the highest doses to the lungs after a single exposure and for two groups with the highest doses after repeated exposure.


Induction of mutations by bismuth-212 alpha particles at two genetic loci in human B-lymphoblasts.

The human lymphoblast cell line TK6 was exposed to the alpha-particle-emitting radon daughter 212Bi by adding DTPA-chelated 212Bi directly to the cell suspension. Cytotoxicity and mutagenicity at two genetic loci were measured, and the molecular nature of mutant clones was studied by Southern blot analysis. Induced mutant fractions were 2.5 x 10(-5)/Gy at the hprt locus and 3.75 x 10(-5)/Gy at the tk locus. Molecular analysis of HPRT- mutant DNAs showed a high frequency (69%) of clones with partial or full deletions of the hprt gene among radiation-induced mutants compared with spontaneous mutants (31%). Chi-squared analyses of mutational spectra show a significant difference (P < or = 0.005) between spontaneous mutants and alpha-particle-induced mutants. Comparison with published studies of accelerator-produced heavy-ion exposures of TK6 cells indicates that the induction of mutations at the hprt locus, and perhaps a subset of mutations at the tk locus, is a simple linear function of particle fluence regardless of the ion species or its LET.


Treatment of radiation nephropathy with captopril.

Both experimental and clinical radiation nephropathy are typically progressive, evolving to kidney failure over weeks to months. Other late radiation injuries (spinal cord, lung) are also progressive and have no known specific antidote. Recent reports of the efficacy of captopril in modifying radiation injury of the lung prompted this trial of captopril in treating established radiation nephropathy. Six months after 15-27 Gy in 12 fractions bilateral renal irradiation, 72 rats with blood urea nitrogen > 4.1 mmol/liter were started on captopril (500 mg/liter) or no drug in the drinking water. Subsequent survival was significantly enhanced in rats receiving captopril as opposed to no drug (P = 0.0013), and the rate of rise of blood urea nitrogen was significantly diminished (P < 0.0001) in the animals on captopril. Urine protein excretion was also reduced from initially elevated levels in the rats on captopril compared to levels in rats given no drug. We conclude that captopril therapy preserves kidney function, reduces proteinuria, and enhances survival in experimental radiation nephropathy.


The combined use of 131I-labeled antibody and the hypoxic cytotoxin SR 4233 in vitro and in vivo.

Radioimmunotherapy is hindered by the slow penetration of antibody molecules into tumors. Cells that are poorly targeted by antibody, because of their distance from feeding blood vessels, receive the lowest radiation dose, and this problem is compounded if there are radioresistant hypoxic cells present. It would be desirable to combine radioimmunotherapy with an agent that is preferentially toxic to these cells. SR 4233 is a potent hypoxic cytotoxin, and it was combined with 131I-NR-LU-10 to treat LS174T human colon adenocarcinoma multicell spheroids and nude mouse xenografts for these studies. Under conditions of severe hypoxia (< 0.01% O2), 2 h of pretreatment or 18 h of simultaneous treatment with SR 4233 did not significantly enhance the effectiveness of 131I-NR-LU-10 in spheroids. However, under aerobic conditions with a 10% fraction of hypoxic cells, there was more toxicity than would be predicted from simple additivity. Xenografts treated with 131I-NR-LU-10 + SR 4233 had a growth delay that was significantly longer than that achieved with 131I-NR-LU-10 alone. In both spheroids and xenografts, combined treatment produced about 10 times more cell killing than 131I-NR-LU-10 alone. The lack of enhancement in spheroids under complete hypoxia suggests that SR 4233 does not sensitize hypoxic cells to radiation damage. The results with aerobic spheroids and in vivo, where a portion of the cells were hypoxic, could be explained by the targeting of different cell populations (hypoxic and aerobic) by each therapeutic modality. This effect should also be enhanced by reoxygenation and reestablishment of the hypoxic fraction during treatment, thus allowing more than the initially hypoxic fraction of cells to be killed by the SR 4233.


Leukotriene C4-induced radioprotection: the role of hypoxia.

Pretreatment of mice with leukotriene C4 (LTC4), a biological mediator that can cause marked contraction of vascular, tracheal, and bronchial smooth muscles, enhances radiation survival. Optimal protection is observed with 10 micrograms LTC4 per mouse (400 micrograms/kg body wt) administered subcutaneously 5 to 10 min prior to irradiation. Pretreatment with 10 micrograms LTC4 increases the LD50/30 from 8.36 Gy in mice receiving saline to 15.7 Gy, providing a dose reduction factor of 1.9. Enhanced survival of mice was observed with doses of 50 micrograms LTD4/mouse, but not with LTE4. Fifteen minutes after administration of 10 micrograms LTC4, the breathing rate is reduced by 33%, the blood paO2 by 20%, the paCO2 by 29%, and the HCO3- by 43%. Whole blood lactate increased by 288% at this same time. The period over which the elevation in blood lactate occurs is similar to the times for optimal radioprotection. These data coupled with the finding that protection was eliminated when irradiation occurred in an enriched oxygen atmosphere indicate that hypoxia plays a role in leukotriene C4-induced animal radiation survival. High-performance liquid chromatography and tissue distribution analyses support a role for an indirect mechanism since the highest levels of LTC4 in the tissues do not correlate with the peak time for radioprotection.


Radioiodinated 1-(2-fluoro-4-iodo-2,4-dideoxy-beta-L-xylopyranosyl)-2-nitroimidazole: a novel probe for the noninvasive assessment of tumor hypoxia.

1-(2-Fluoro-4-iodo-2,4-dideoxy-beta-L-xylopyranosyl)-2-nitroimidazole (FIAZP) has been synthesized and labeled with radioiodine (125I). Radioiodinated FIAZP is one of a series of sugar-coupled 2-nitroimidazoles developed in our laboratory as probes for noninvasive scintigraphic assessment of tumor hypoxia. An in vivo biodistribution study with [125I]FIAZP in the murine BALB/c EMT-6 tumor model showed a tumor-to-blood ratio of 6, 24 h after injection, with 0.5% of the injected dose present per gram of tumor. These values are several times higher than the respective ratios and distribution values in any of the organs, with the exception of liver. Radioactivity from tissues other than tumor and liver declined with time, following the decline of blood radioactivity. Rapid whole-body elimination of radioactivity was observed (> 96% in 24 h). The thyroid showed little uptake of radioactivity, indicating minimal in vivo deiodination. 1-(2-Fluoro-4-iodo-2,4-dideoxy-beta-L-xylopranosyl)-2-nitroimidazo le appears to undergo hypoxia-dependent binding in tumor tissue at levels comparable to those of other sugar-coupled 2-nitroimidazoles. The potential for imaging with this compound is discussed.


Effect of dose rate on the survival of irradiated human skin fibroblasts.

The survival of cells in density-inhibited, confluent cultures maintained at 37 degrees C was examined following exposure to 137Cs gamma rays at low dose rates (0.023 or 0.153 Gy/h) or to 60Co gamma rays at a single high dose rate (0.70-0.75 Gy/min). Cells from an ataxia telangiectasia (AT) homozygote showed no dose-rate effect, whereas a three- to fivefold increase in D0 was observed for all other cell strains exposed at low dose rates. The magnitude of the dose-rate effect did not differ significantly among cells from persons with hereditary retinoblastoma, basal cell nevus syndrome, or AT-heterozygote compared with normal cell strains, and was not related to the size of the shoulder (extrapolation number) of the survival curve. Furthermore, no differences in the capacity for the repair of potentially lethal damage during confluent holding were observed among these latter cell strains.


5-lipoxygenase inhibitors and their anti-inflammatory activities.

A wide variety of agents have been reported as 5-LO inhibitors. The majority of the series appear to be lipophilic reducing agents, including phenols, partially saturated aromatics, and compounds containing heteroatom-heteroatom bonds. Many of these are not selective 5-LO inhibitors, but often affect CO and other LOs as well. In vivo systemic activity for many of these has been, in general, disappointing, probably because of poor bioavailability caused by lipophilicity and metabolic instability (oxidation, and conjugation of phenolic compounds). However, topically a number of agents have shown promise for skin inflammation, with Syntex's lonapalene the most advanced of these. Most results published to date appear more disappointing in the allergy/asthma field. More excitingly, a few structural types are selective 5-LO inhibitors which have shown systemic activity in vivo and in the clinic. Abbott's zileuton (136) appears to be one of the leading compounds in this category, along with other hydroxamates such as BW-A4C (129) from Burroughs-Wellcome. Recent selective non-reducing agents such as Wyeth-Ayerst's Wy-50,295 (143) and the similar ICI compounds such as ICI 216800 (145) also hold promise. The enantiospecific effects of (106) and (145) are especially interesting for the design of new inhibitors. If compounds like these validate the hypothesis that inhibition of 5-LO will have a significant anti-inflammatory effect, a redoubling of effort throughout the industry to find second- and third-generation selective agents may be expected. Part of the difficulty in interpreting and comparing the 5-LO literature is the plethora of test methods and activity criteria. As pointed out in the introduction, inhibition of product release from cells, often stimulated with A23187, has commonly been used to demonstrate 5-LO inhibition. However, this type of assay cannot be assumed to be diagnostic for 5-LO inhibition. Only if specificity for 5-LO product generation and (ideally) activity in cell-free enzymes is also shown should mechanistic interpretations be made. Recently, a new class of compounds was found at Merck which inhibited LT biosynthesis without inhibiting 5-LO, but apparently by a novel, specific mechanism. L-655,240 (169) and L-663,536 (MK-886) (170) were both active in human ISN, with IC50 values in the low micromolar range. Both also orally inhibited GPB (< 1 mg/kg). MK-886 was effective in Ascaris-induced asthma in squirrel monkeys, in rat carrageenan pleurisy, in rat Arthus pleurisy, and (topically) in guinea-pig ear oedema induced by A23187.(ABSTRACT TRUNCATED AT 400 WORDS)


The production of arachidonic acid metabolites in rat testis.

There is growing evidence that arachidonic acid is oxygenated enzymatically in every cell type and that the oxygenated metabolites regulate a variety of pathological and physiological processes including reproduction. In the present study, the metabolism of arachidonic acid in the testis via cyclooxygenase and lipoxygenase pathways was analyzed. Testicular microsomes showed substantial cyclooxygenase activity as measured by the polarographic method. Analysis of the products on TLC revealed PGF2 alpha (79.5%) as the main product followed by PGE2 (20.3%) and PGD2 (0.17%). At higher substrate concentrations (150 microM), however, 6-keto-PGF1 alpha, the stable metabolite of prostacyclin, was observed in substantial quantities. Maximum activity of lipoxygenase was observed at pH 6.4 in both microsomes and cytosol, the activity being higher in cytosol. Analysis of lipoxygenase pathway products with arachidonic acid as the substrate, revealed the presence of 12-HPETE as the major product both in cytosol and in microsomes. Besides this, 15- and 5-HPETEs were also observed in substantial quantities.


Jugular plasma concentrations of 13,14-dihydro-15-keto-prostaglandin F2 alpha in prepubertal beef heifers treated with progestogen then challenged with oxytocin.

Prepubertal Angus crossbred heifers (n = 24) between 8 and 10 mo of age were used to determine if progestogen treatment would enhance jugular concentrations of 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) after oxytocin (OT) injections. Heifers were stratified by age and weight and allotted to randomized treatments in a 2 x 2 factorial arrangement. Heifers were treated with either a norgestomet (NOR) implant (6 mg) for 9 d or no implant (0 mg; BLK). On d 8 of NOR treatment, jugular veins were catheterized and, on d 9, blood samples were collected every 15 min for 165 min. The first four samples were used to determine basal PGFM concentrations (an indirect measure of uterine PGF2 alpha release). After collection of the fourth sample, either OT (100 IU) or saline (0 IU; SAL) was injected via the jugular catheter. After the 165-min sample was collected, NOR implants were removed. Beginning 48 h after implant removal, a second 165- min blood sampling period was initiated. Average progesterone concentrations were less than 1 ng/ml during both bleeding periods. Within treatment, PGFM concentrations were similar between the first and second sampling periods; therefore, data within treatment were combined. Basal PGFM concentrations were higher (P < .01) in NOR-treated than in BLK heifers. Oxytocin did not increase PGFM concentrations in BLK-OT heifers; however, a marked increase in PGFM was detected in the NOR-OT heifers in response to oxytocin. Average PGFM concentration was greatest (P < .0001) in NOR-OT heifers, and PGFM profiles differed (P < .0001) between NOR-OT and each of the other treatment groups. Results from this study indicate that NOR increases basal PGFM and may "condition" the uterus to respond to OT in prepubertal heifers.


Intrauterine infusion of prostaglandin E2 and subsequent luteal function in cattle.

The objective was to evaluate the effect of intrauterine infusion of prostaglandin E2 (PGE2) on luteal function in cattle. Heifers and cows were randomly assigned after two normal estrous cycles to either PGE2 or control treatment groups. Females in Treatment A were infused with 1 mg of PGE2 once daily into the uterine horn ipsilateral to the corpus luteum between days 7-10 of the estrous cycle with a 0.25 ml plastic semen straw and an artificial insemination pipette. Females in Treatment B were similarly infused with 1 mg of PGE2 once daily in 20 ml of a carrier vehicle via a catheter on days 10 and 11 of the estrous cycle. Control animals were infused with the carrier vehicle using either a semen straw (Treatment C) or via a catheter (Treatment D) on the same days of the estrous cycle. Blood samples were collected daily to monitor plasma progesterone concentrations during the treatment period. Females infused with PGE2 on days 7-10 of the estrous cycle returned to estrus in a mean of 23.5 days (range 22-25 days) and were similar (P > 0.05) to those infused on days 10 and 11 which returned to estrus in 23.5 days (range 22-25 days). Animals similarly infused with carrier vehicle on the same days of the estrous cycle returned to standing estrus in 20.2 days (range 17-23 days). Plasma progesterone concentrations indicated an extended period of elevated progesterone concentrations in PGE2-treated animals compared with control animals. These results indicate that short term administration of PGE2 early in the estrous cycle may result in extended luteal maintenance.


Effects of thromboxane synthase and cyclooxygenase inhibition on PAF-induced changes in lung function and arachidonic acid metabolism.

PAF was administered as an intravenous bolus (0.1 micrograms/kg) to eight chronically instrumented awake sheep. The effects of pretreatment with an inhibitor of cyclooxygenase (meclofenamate) on PAF-induced changes in lung function were compared to those observed with a specific inhibitor of thromboxane synthase (DP1904). Each animal was studied four times in varied order: PAF alone, PAF + DP1904, PAF + meclofenamate, and DP1904 alone. Saline alone (control), DP1904 alone, and meclofenamate alone did not cause changes in any of the measured variables. DP1904 and meclofenamate significantly attenuated the PAF-induced fall in lung compliance, elevation in peak pulmonary artery pressure, and increased lung lymph flow. Both drugs abolished the PAF-induced increases in lung lymph thromboxane B2 concentrations. Meclofenamate, but not DP1904, blocked the rise in lymph 6-keto-PGF1 alpha. Although meclofenamate blocked the rise in lymph PGE2, DP1904 resulted in levels 2.7 times higher than PAF alone. We conclude that: (1) inhibition of thromboxane synthase is as effective as inhibition of cyclooxygenase in attenuating PAF-induced changes in lung function, and (2) thromboxane synthase inhibition results in augmented production of PGE2 following PAF administration in vivo.


Oxidative metabolism of N-phenyllinoleamide by human nasal polyps.

N-phenyllinoleamide (NPLA), the anilide of linoleic acid, has been associated with the epidemiology of Toxic Oil Syndrome, but no data are available on its metabolism. On account of the similarity in chemical structure between the linoleic acid and NPLA, the aim of this study has been to investigate the oxidative metabolism of this xenobiotic by the human nasal polyp, a tissue with elevated 15-lipoxygenase activity. For this purpose, tissue homogenates have been incubated for 2 h with NPLA (0.1 mM) spiked with either N-(ring G-3H)PLA (0.2 microCi/ml) or N-P(1-14C)LA (0.05 microCi/ml). Gas chromatographic/mass spectrometric analysis of the high performance liquid radiochromatographic fractions shows that the 9,12,13-trihydroxy, 12,13-epoxy-11-hydroxy and 13-hydroxy NPLA derivatives are the major metabolites. These results revealed that NPLA metabolites are chemical structures related to the linoleic acid derivatives, some of which may show biological activity.


[Diagnostic value of antibodies against HIV-1 proteins in seropositive drug addicts tested by the western blotting method].

The incidence of various patterns of antibodies against HIV 1 proteins was tested by Western blot in EIA--positive serum samples from intravenous drug abusers. The presence of anti-p24, anti-gp160 and anti-gp120 antibodies was the most typical pattern suggestive for early humoral response. In most instances of indeterminate results subsequent WB tests performed during 4 to 6 week period showed whole spectrum of anti-HIV 1 antibodies.


Incentive learning following reinforcer devaluation is not conditional upon the motivational state during re-exposure.

Three experiments analysed the effect of re-exposure to the reinforcer following aversion conditioning on instrumental performance. In the first experiment, groups of hungry and thirsty rats were trained to press a lever for sucrose, which was then followed by a single injection of lithium chloride (LiCl). On the following day, half the animals in each motivational condition received re-exposure to the sucrose solution; the remaining animals were not re-exposed. In a subsequent extinction test animals that had received re-exposure to the sucrose pressed less than animals that were not re-exposed. Moreover, the effect of re-exposure to the sucrose solution was similar following training under hunger and thirst. In the remaining studies, animals were trained to lever-press for sucrose while either hungry or thirsty. They were then injected with LiCl and re-exposed to the sucrose while either hungry or thirsty, i.e. in the same or different motivational state employed during training, or they were not re-exposed. Lever pressing was then tested in extinction in the training motivational state. As in the first experiment, re-exposure to the reinforcer after aversion conditioning enhanced the magnitude of the reinforcer devaluation effect. More importantly, re-exposure to the sucrose produced a comparable effect on instrumental performance, whether re-exposure was given under the same or different motivational state to that employed during training. These results suggest that the instrumental reinforcer devaluation effect depends upon a process of incentive learning, but that this process is not conditional upon the current motivational state of the animal.


Signalling and incentive processes in instrumental reinforcer devaluation.

We have previously reported that conditioning an aversion to the reinforcer using an isotonic lithium chloride (LiCl) solution following instrumental training reduces performance in a subsequent extinction test only if animals are re-exposed to the reinforcer prior to the test. Rescorla (1992), in contrast, reported an immediate devaluation effect using a hypertonic LiCl solution that did not depend upon re-exposure. In two experiments we examined the effect of using a hypertonic LiCl solution to condition the aversion to the reinforcer on subsequent instrumental performance in extinction, with and without re-exposure. In Experiment 1 thirsty rats were trained to press a lever for a sucrose solution before being injected with 0.6 M LiCl either immediately or after a delay. Half of the immediate and delay groups were then re-exposed to the sucrose in the absence of the lever, with the remainder being exposed to water. Contrary to the previously reported effects of isotonic LiCl, a hypertonic solution induced a reinforcer devaluation effect in all the immediately poisoned animals, which did not depend upon re-exposure to the reinforcer. In Experiment 2 the possibility that this devaluation effect was induced by the discomfort associated with the hypertonicity of the solution was assessed by replicating Experiment 1 but, in addition, using two immediately poisoned groups given the LiCl injection under anaesthesia. In the absence of anaesthesia, the devaluation effect observed without re-exposure to the reinforcer in Experiment 1 was replicated. When the injection was given under anaesthesia, however, a reinforcer devaluation effect was observed only in animals that were re-exposed to the reinforcer prior to the extinction test. These results were interpreted as evidence that a reinforcer devaluation effect induced by pairing the reinforcer with illness depends upon a process of incentive learning, whereas a devaluation effect mediated by learning a signalling relationship between the reinforcer and somatic discomfort does not.


Potentiation by a taste of toxicosis-based context conditioning: effects of varying the test fluid.

Rats that drank water in a distinctive environment and were then injected with lithium chloride (water-lithium condition) were compared with those given an added taste on those conditioning sessions (sucrose-lithium condition). In three experiments this taste potentiated a conditioned aversion to the context, as measured by suppression of intake of another solution: either a novel sour taste (Experiments 1 and 2) or a familiar saline solution (Experiment 3). In contrast, this potentiation effect was not detected when subjects were tested with water, whether a high or low dose of lithium was used (Experiment 2). Instead, in Experiments 1 and 2 water-lithium subjects drank less water than did the sucrose-lithium subjects on such tests i.e. an apparent overshadowing effect, which was the opposite outcome to that found previously using almost identical procedures. Intake on recovery sessions in another context suggested that, when water is used as the test fluid, potentiation can be masked by two factors: a context-dependent aversion to water in water-lithium subjects, and a conditioned inhibition effect of water in sucrose-lithium subjects. These may account for previous failures to detect potentiation of context conditioning.


Contextual factors in neophobia and its habituation: the role of absolute and relative novelty.

In four experiments we investigated the role of contextual cues in the habituation of neophobia in rats. Experiment 1 showed that the consumption of a novel flavour increased across a series of presentations in one context (A) but fell when the flavour was subsequently presented in a second, novel, context (B). In Experiments 2 and 3, subjects again received exposure to a flavour in context A, but also were familiarized with the test context, B. These subjects consumed the flavour with equal readiness, whether it was presented in Context A or in Context B at test. Experiment 4 replicated the results of Experiment 1 and also showed that the consumption of a novel flavour was not influenced by whether it was presented in a novel or a familiar context. Several mechanisms by which the novelty or familiarity of the context might interact with the novelty or familiarity of the flavour were discussed.


Calcitonin gene-related peptide neurons innervating the canine digestive system.

The pattern of nerve cells and fibers containing calcitonin gene-related peptide immunoreactivity (CGRP-IR) was investigated in the canine digestive tract by means of immunohistochemistry. CGRP-IR nerve fibers innervate all the layers of the gut, including the vasculature, with different densities depending on the region. CGRP-IR processes are sparse in the esophagus and stomach, where they are mostly confined to the enteric plexuses and vasculature. CGRP-IR fibers are quite abundant in the small and large intestine, where they form dense arborizations in the mucosa, and are numerous in the muscularis mucosae, deep muscular plexus and circular muscle. The myenteric and submucous plexuses of the intestine contain dense networks of CGRP-IR fibers and numerous CGRP-IR ganglion cells. On the other hand, in the enteric ganglia of the esophagus and stomach, in the intrapancreatic ganglia and in the ganglionated plexus of the gallbladder, CGRP-IR is restricted to non-varicose processes. A moderate density of CGRP-IR fibers supplies the endocrine and exocrine pancreas, and the fibromuscular layer and lamina propria of the gallbladder. The density of CGRP innervation in different regions can be summarized as follows: intestine >> pancreas and gallbladder > or = antrum > cardia > gastric corpus and distal esophagus. CGRP- and tachykinin (TK)-IRs are colocalized in a substantial population of fibers, particularly those distributed to the mucosa, muscularis mucosae and vasculature, whereas there was no evidence of colocalization in intrinsic ganglion cells. The present results suggest that (1) the CGRP innervation of the dog digestive system includes an intrinsic and an extrinsic component, and (2) CGRP- and TK-IRs are co-expressed in extrinsic nerve fibers. These findings extend previous observations in rats and guinea pigs and provide insights into the sites of action of CGRP in the digestive system of the dog, which has served as a model for CGRP functional studies.


Enzymatic degradation of endothelin-1 by activated human polymorphonuclear neutrophils.

Endothelin-1 (ET-1) is a potent vasoconstrictor peptide secreted by endothelial cells. We investigated whether polymorphonuclear neutrophils (PMN) were able to destroy this peptide by enzymatic hydrolysis produced either by the membrane-bound endopeptidase 24.11 or by lysosomal proteinases released in the medium by activated cells. Resting and activated PMN were incubated with 125I-labelled ET-1 and the degradation fragments were analyzed by HPLC. A marked degradation of ET-1 was observed only in the presence of the stimulated cells, leading to the generation of seven radiolabelled peaks. Addition of phosphoramidon had no effect on the appearance of these metabolites, while soybean trypsin inhibitor abolished almost completely the degradation of the peptide, suggesting a role of cathepsin G in ET-1 hydrolysis. Among the purified leukocyte enzymes tested, cathepsin G hydrolyzed 125I-labelled ET-1 at the higher rate and gave rise to two radiolabelled peaks already observed in the presence of activated PMN. Incubation of unlabelled ET-1 with purified cathepsin G allowed to identify a major cleavage site corresponding to the His16-Leu17 bond, leading to the formation of inactive [1-16] fragments and the C-terminal pentapeptide. This mechanism of ET-1 inactivation could play a role in acute inflammatory reaction where PMN adhere to the vascular endothelial cells.


Plasma concentration of neuropeptide Y in patients with adrenal hypertension.

The mechanisms of hypertension during primary hyperaldosteronism and Cushing's syndrome are not completely understood. An enhanced vascular sensitivity to noradrenaline has been described in both situations. Neuropeptide Y (NPY) induces direct vasoconstriction and potentiates the action of noradrenaline. Sodium retention and dexamethasone have been shown to increase circulating NPY levels in animals and the expression of NPY in neuroendocrine cells. In order to determine if NPY could be involved in the enhanced vascular sensitivity to noradrenaline associated with adrenocortical hyperactivity, we measured plasma NPY in patients with Cushing's syndrome (n = 26) and primary hyperaldosteronism (n = 15) and compared it with that of hypertensive patients with pheochromocytomas (n = 13) or essential hypertension (n = 51) and with normotensive controls (n = 47). The concentration of NPY-Like immunoreactivity (NPY-Li) (mean +/- S.E.) in controls was 39.6 +/- 3.0 pg/ml. Elevated concentrations were found in 77% of the samples collected from pheochromocytoma patients (1180.4 +/- 394.0 pg/ml). NPY-Li levels in patients with essential hypertension (35.0 +/- 2.6 pg/ml), primary hyperaldosteronism (31.3 +/- 3.9 pg/ml) and Cushing's syndrome (33.1 +/- 4.8 pg/ml) were not different from that of controls. NPY-Li levels in hypertensive and normotensive patients with Cushing's syndrome were similar (38.5 +/- 7.5 vs 24.2 +/- 3.7 pg/ml). No correlation was found between the NPY-Li level and the mean blood pressure at the time of sampling. Our results suggest that NPY is unlikely to be involved in the pathogenesis of hypertension associated with primary hyperaldosteronism and Cushing's syndrome.


Structure-function studies of five natural, including catfish and dogfish, gonadotropin-releasing hormones and eight analogs on reproduction in Thai catfish (Clarias macrocephalus).

Five distinct forms of gonadotropin-releasing hormone (GnRH) and their analogs, six of which are newly designed, were used to study reproduction in Thai catfish, Clarias macrocephalus. Determination was made for the percentage of fish that ovulated within 16-18 h; the percentage of eggs fertilized; and the percentage of larva that hatched and survived for 7 days. The results show, firstly, that natural chicken GnRH-II, which is identical with catfish GnRH-II, was significantly more effective at a dose of 300 micrograms/kg than the control injection for the induction of ovulation. Dogfish GnRH at the same dose was also significantly more effective than the control, but was not significantly different from chicken (catfish) GnRH-II for ovulation induction. The novel catfish GnRH-I, mammalian GnRH and salmon GnRH were not effective at 100, 150 or 300 micrograms/kg in Thai catfish. Secondly, 5 of 8 analogs of GnRH at a dose of 20 micrograms/kg resulted in a significantly higher percentage of ovulating fish compared with the control fish. Among these five analogs, the most effective were the two analog forms of chicken GnRH-II (D-Arg6,Pro9 NEt and D-Nal6,Pro9 NEt), followed by the salmon GnRH analog (D-Arg6,Pro9 NEt), a dogfish GnRH analog (D-Arg6,Pro9 NEt) and the mammalian GnRH analog (D-Ala6,Pro9 NEt). Not significantly different from the controls were the two catfish GnRH-I analogs and one of the dogfish (D-Nal6,Pro9 NEt) analogs. The six new analogs had not been previously tested in any animal. Thirdly, the number of fish ovulating was the same whether GnRH was administered in one or two injections.


Human epidermal growth factor-on molecular forms present in urine and blood.

A sensitive enzyme-linked immunosorbent assay (ELISA) for quantitation of human epidermal growth factor (EGF) was employed to study EGF in urine and blood. The EGF/creatinine ratio in urine was significantly higher for women (range and (median); 0.20-0.83 (0.50) nmol EGF/mmol creatinine) than for men (0.17-0.63 (0.30) nmol EGF/mmol creatinine). We were not able to demonstrate EGF in plasma (median plasma EGF < 0.01 nmol/l) whereas serum contained a range and (median) of 0.02-0.31 (0.12) nmol EGF/l. The amount of EGF in serum showed a weak correlation to the platelet count (r = 0.327). EGF was partly purified by affinity chromatography from urine (urine EGF) and from activated platelets in platelet rich plasma (blood EGF). Both blood and urine contained a high molecular weight form of EGF (HMW EGF) as well as 6 kDa EGF. HMW EGF from blood was similar to HMW EGF from urine concerning behaviour upon gel filtration, pI and apparent affinity constant for binding to the EGF receptor. However, HMW EGF constituted approx. 40% of blood EGF but only 10% of urinary EGF. The 6 kDa EGF from both blood and urine contained two isopeptides with pI around 4.40 and 4.15 but in various proportions. The apparent affinity constant for binding to the EGF receptor for blood 6 kDa EGF was 1.8 x 10(10) l/mol compared to 1.0 x 10(10) l/mol for urinary 6 kDa EGF and 0.8 x 10(10) l/mol for HMW EGF from both blood and urine. The present study suggests that the processing of the EGF precursor differs in the blood and in the kidneys and that 6 kDa EGF from blood and urine binds to the EGF receptor with a higher apparent affinity constant than does HMW EGF.


Degradation and inactivation of rat atrial natriuretic peptide 1-28 by neutral endopeptidase-24.11 in rat pulmonary membranes.

Atrial natriuretic peptide (ANP), a 28-residue peptide with cardiovascular and renal effects, is rapidly cleared from the circulation. Beside renal clearance, an extra-renal metabolism by the enzyme neutral endopeptidase-24.11 (NEP-24.11) has been proposed, since specific NEP-24.11-inhibitors increase endogenous plasma-ANP. NEP-24.11 is present in rat lung but its significance for ANP hydrolysis within the lung is unclear. The aim of this study was to investigate a possible degradation of rat ANP in a membrane preparation from rat lung. Hydrolysis products of ANP were separated by HPLC and further characterized by a pulmonary artery bioassay, by radioimmunoassay with different antisera, by peptide sequencing and by masspectrometry. Rat pulmonary membranes degraded ANP to one main metabolite lacking biological activity and with poor cross-reactivity to an antiserum recognising the central ring-structure of the peptide. Formation of the hydrolysis product was prevented by the NEP-24.11-inhibitor phosphoramidon (1 microM). Peptide sequencing of the metabolite revealed a cleavage between Cys7 and Phe8, which was confirmed by mass-spectrometry. The metabolite had an HPLC elution time identical to that of the product formed by purified porcine NEP-24.11. These findings suggest that ANP is metabolized and inactivated by endopeptidase-24.11 in rat lungs, the first organ exposed to ANP released from the heart.


Role of cholecystokinin in the intestinal fat- and acid-induced inhibition of gastric secretion.

This study was designed to determine the role of cholecystokinin (CCK) in the inhibition of gastric HCl secretion by duodenal peptone, fat and acid in dogs with chronic gastric and pancreatic fistulas. Intraduodenal instillation of 5% peptone stimulated both gastric HCl secretion and pancreatic protein secretion and caused significant increments in plasma gastrin and CCK levels. L-364,718, a selective antagonist of CCK-A receptors, caused further increase in gastric HCl and plasma gastrin responses to duodenal peptone but reduced the pancreatic protein outputs in these tests by about 75%. L-365,260, an antagonist of type B receptors, reduced gastric acid by about 25% but failed to influence pancreatic response to duodenal peptone. Addition of 10% oleate or acidification of peptone to pH 3.0 profoundly inhibited acid secretion while significantly increasing the pancreatic protein secretion and plasma CCK levels. Administration of L-364,718 reversed the fall in gastric HCl secretion and significantly attenuated pancreatic protein secretion in tests with both peptone plus oleate and peptone plus acid. Exogenous CCK infused i.v. in a dose (25 pmol/kg per h) that raised plasma CCK to the level similar to that achieved by peptone meal plus fat resulted in similar inhibition of gastric acid response to that attained with fat and this effect was completely abolished by the pretreatment with L-364,718. We conclude that CCK released by intestinal peptone meal, containing fat or acid, exerts a tonic inhibitory influence on gastric acid secretion and gastrin release through the CCK-A receptors.


[Color-Doppler instruments: their design principles and modes of use].

The use of color-Doppler US equipment allows the clinician to evaluate, at the same time and within the same image, both shape and structure of the examined organs and the flow patterns in the vessels within them. Such information as direction and velocity of blood flow are displayed with a variety of intravascular colors, according to a conventional code. Moreover, this diagnostic method can provide physiological and anatomical pieces of information in the same image and is therefore widely used in medical imaging. However, the images obtained by means of color-Doppler units are not always easy to understand and diagnostic misinterpretations may occur. In this paper we will summarize the physical and technological principles on which such units are based. In the first half of paper, the problems relative to acquisition and construction of the images are presented, together with the different technical approaches used to obtain flow velocity information. Moreover, the relationships between the "black-and-white" and the "color" parts of the images are described. The principles according to which color is assigned to vessels are reported, together with the patterns exhibited by a vessel according to the type of transducer used to examine it. The non-linear correlation between the color scale and flow velocities is also discussed. The second half of the paper deals with technical parameters of color-Doppler scanning, discussing the criteria of choice of transducers, the determination of Doppler angle, the setting of both wall filters and scanning depth. The problem of pulse repetition frequency (PRF) setting is also addressed; this parameter is especially critical in color-Doppler studies. The authors believe that careful setting of all examination parameters and the good knowledge of the physical and technological factors underlying color-Doppler images are the basis for a correct and useful approach to this fascinating technique.


[Neuronal migration anomalies. The magnetic resonance aspects of some types].

The authors investigated the value of magnetic resonance (MR) imaging in the evaluation of some types of neuronal migration anomaly. During pregnancy, a radial neuronal migration from germinal matrix to cortex occurs in the fetal brain, and 6 layers are formed. Infections, traumas, vascular factors can block the migration. Neuronal migration disorders are divided into 5 different classes: (1) agyria-pachigyria complex; (2) schizencephaly; (3) polymicrogyria; (4) unilateral megaencephaly; (5) heterotopia. In this study, 12 patients were evaluated with MR imaging: 5 had lissencephaly, 4 heterotopia and 3 schizencephaly (2 with open lips, and 1 with closed lips). MR imaging is the method of choice in these patients; indeed, characteristic morphologic and signal patterns allow the correct evaluation and diagnosis of neuronal migration anomalies in all cases.


[Magnetic resonance angiography with gadolinium (Gd-DTPA) versus baseline magnetic resonance angiography in the study of the intracranial circulation].

The authors evaluated the role of GdDTPA in magnetic resonance angiography (MRA) of intracranial vessels. Fifteen patients affected with different conditions underwent MRA of intracranial vessels before and after paramagnetic contrast medium infusion. A superconductive 1.5-T magnet (Magnetom Siemens) was used, and a head circular coil, together with the 3DFT TOF technique. The enhanced exam was performed following the infusion of 0.2 ml/kg of GdDTPA in about 2 minutes, with simultaneous MRA image acquisition. To compare enhanced with unenhanced images relative to signal intensity, the signal increase at the basilar artery and carotid sinus was studied, together with signal-to-noise (S/N) ratio and spatial resolution. During acquisition, enhanced MRA images at the basilar artery showed a mean intensity value of 423.8 +/- 33.2 vs 357.8 +/- 53.2 of unenhanced scans; a statistically significant difference (p < 0.05; p < 0.01) was observed in favor of enhanced images. At the carotid sinus, enhanced MRA showed 184.5 +/- 28.4 mean intensity value vs 190.5 +/- 19.8 of unenhanced exams; no statistically significant difference was observed (p < 0.05; p < 0.01) in favor of unenhanced exams. At the basilar artery the S/N ratio of baseline exams was 1.9 vs 2.2 for enhanced scans; at the carotid sinus S/N ratio was 2.4 (unenhanced) vs 2.3 (enhanced). Thus, MRA allowed better visualization of peripheral branches of arterial (95.6%) and venous vessels, which unenhanced scans always failed to depict; on the other hand, enhanced images exhibited poorer definition of arterial vessels which were never isolated from the background. The simultaneous visualization of arterial and venous vessels, of choroid plexus and mucosae, affect the quality of enhanced angiograms. At present, GdDTPA is the sole contrast medium suitable for MRA intracranial vessels even though, due to its pharmacokinetic features, it is not the optimum medium.


[The use of the single-pulse RARE sequence in the study of the cerebrospinal axis].

The authors describe a fast MR sequence allowing to obtain a myelographic-like, markedly T2-weighted, image quite similar to conventional myelographies. Relative to conventional spin-echo sequences, in which echoes are encoded so as to achieve the same phase, each echo of the sequence here employed is given a different phase encoding. The sequence, called MYUR (myelography-urography) is based on the generation, after a 90 degrees pulse, of a "train" of 256 echoes, each one phase-encoded differently, by multiple 180 degrees pulses, producing a single image. The total duration of such a sequence, with 2 repetitions, is 21 seconds. The MR myelographic sequence allows to univocally study tissues with a very long T2 relaxation time; under normal conditions, only cerebrospinal fluid, urine and bile are demonstrated. A resistive MR unit operating at 0.28 T was employed in the present study. MR myelography is capable of pointing out an eventual dural sac compression or a space-occupying mass, thus allowing an effective scout-view to center the subsequent pulse sequences; all MR-myelographic exams need to be completed with other short and long TR sequences.


[SPECT in the study of pathology of the temporomandibular joint. The authors' personal experience].

Symptomatic temporomandibular joint dysfunctions may affect about 25% of the adult population, with a smaller though significant percentage of patients experiencing severe impairment. From 1986 through 1991, 107 patients with severe temporomandibular joint symptoms and with various temporomandibular joint disorders were evaluated with conventional radiology and with closed/open-mouth temporomandibular joint tomograms. Single-photon emission-computed tomography (SPECT) and planar imaging were performed on 32 patients using a rotating gamma camera equipped with a general purpose collimator. Transaxial, coronal and sagittal tomoscintigrams were reconstructed. Increased radiotracer uptake in the temporomandibular joint was regarded as a positive finding, and the intensity of temporomandibular joint activity was compared with that of adjacent calvarium using regions of interest. In the 32 patients submitted to scintigraphy, conventional radiology showed no pathologic patterns, while SPECT showed pathologic findings in 31 patients (97% of cases). The patient with normal temporomandibular joint findings on SPECT exhibited abnormal maxillary isotope uptake, ipsilateral to the symptoms. Our results indicate that SPECT is a simple, noninvasive, inexpensive and very sensitive screening test relative to the internal derangement of the temporomandibular joint. Moreover, it provides information which is not available by means of routine bone scans or X-ray studies. Thus, SPECT appears to be the modality of choice for patients whose clinical findings are equivocal or whose symptoms are unclear, and it can guide treatment strategies and be useful in the follow-up.


[Magnetic resonance and arthroscopy of the knee. A double-blind study in 40 patients].

To evaluate the capabilities of ultra-low-field MR for the high-resolution imaging of the knee with a short acquisition time, a prospective double-blind study was carried out on 40 consecutive patients with acute or chronic articular conditions who were examined with both MR imaging and arthroscopy. Three-dimensional gradient-echo MR sequences were employed which allow many thin high-resolution slices to be obtained in a relatively short time. To evaluate the results arthroscopy, performed the day after MR imaging, was considered the gold standard. MR imaging and arthroscopy were in agreement in 84.6% of meniscal tears with 91.6% sensitivity and 80% specificity, in 82% of anterior cruciate ligament lesions with 100% sensitivity and 80% specificity and in 81% of cartilage lesions with 100% sensitivity and 61% specificity. On the whole, MR imaging and arthroscopy were in agreement in 82.5% of cases with 97.2% sensitivity and 75.3% specificity. MR imaging gave more information about collateral ligament, muscle and bone involvement. These results confirm the capabilities of ultra-low-field MR imaging in the study of the knee: the technique allows diagnostic studies to be performed in a short time, at a low cost, and with similar results to those obtained with higher field strengths.


[The radiology of osteogenesis imperfecta].

The term "osteogenesis imperfecta" refers to a heterogeneous group of hereditary diseases characterized by osteopenia, increased bone fragility, blue sclerae and dentinogenesis imperfecta. The abnormal synthesis of type-I collagen is responsible for the pathologic changes occurring not only in bone, but also in skin, tendons and ligaments, sclerae and teeth. The clinical and radiographic features of 5 cases (2 males and 3 females; age range: 1 month to 29 years) were analyzed. The patients were unrelated with each other. The diagnosis of the different types of osteogenesis imperfecta is as difficult as the identification of the various genotypes which are responsible for the different clinical pictures. The most characteristic radiographic pattern--which is observed in any type of the disease--consists in osteopenia associated, in most cases, with multiple fractures and deformities--e.g., micromelia, large metaphysis, archon long bones. Typically, "pop corn" calcifications are observed in both epiphysis and metaphysis of long bones. Dentinogenesis imperfecta is one of the most significant clinical patterns, and it can be the only bone abnormality. The prognosis of osteogenesis imperfecta is as varied as its genetics--i.e., the fractures discovered at birth are not necessarily a negative prognostic sign.


[The incidence and role of the os acromiale in the acromiohumeral impingement syndrome].

Os acromiale (an apparently supernumerary bone) corresponds to persistence of the lateral end of acromion ossification nucleus over 18 years of age. Os acromiale is articulated with the clavicle and the base of acromion; its incidence is high and often bilateral. A rarer variant is secondary os acromiale, lying between acromion and great humeral tuberosity. Both variants predispose to the onset of pain due to acromiohumeral impingement. Rotator cuff tears are frequently associated due to direct injury to subacromial compartment structures and to overtraction of acromiocoracoid ligament following functional overuse. Three hundred and ninety-eight patients were examined (313 males and 85 females, aged 12 to 71 years): 265 of them underwent conventional radiography with specific projections for the shoulder and 133 underwent CT. Dysplasia was observed in 9.55% of cases (38 patients), which is in agreement with reports by other authors. CT demonstrates the presence of os acromiale better than specific radiographic projections, without requiring painful patient positioning. Axial CT scans allow the depiction of subacromial compartment structures that cannot be demonstrated by US. The evident and frequent association of arthrotic-degenerative acromioclavicular alterations even after os acromiale assimilation confirms the close relationship of the latter bone to rotator cuff conditions, especially to rotator cuff tears. In our opinion, the correct description of this finding has high prognostic value in the subjects likely to experience functional shoulder overuse and allows the correct etiopathogenesis of pain. Therefore CT, which is an elective imaging method especially suited to demonstrate calcium-density structures, thanks to its high spatial and contrast resolution, can be used concurrently with MR imaging because it is less expensive and more easily available.


[The T1 time dependence of water measured in normal and neoplastic lung tissues].

The authors determined the time dependence of the average T1 relaxation time for the constitutive water of normal and neoplastic lung tissues. In healthy tissues, the T1 dependence appears strictly as a single decaying exponential function down to a threshold value which is invariant over time. The time change of T1 in neoplastic tissues is represented by monoexponential functions, in the short and long run, with a sudden drop 2 weeks after beginning measurements. Moreover, the time dependence is independent of the examined variant of epidermoid carcinoma. We report the kinetic constants of the in vitro aging of the tissues. The presence of a cooperative process, involving neoplastic lung water, to explain the features of aging changes, is also suggested.


[Thoracic localizations of extramedullary erythropoiesis].

A series of 8 patients affected with hemolytic beta thalassemia with intrathoracic extramedullary hematopoiesis is reviewed. All patients were studied with conventional radiologic techniques and with CT and MR imaging. There was good correlation between conventional radiology findings and MR and CT results. CT and MR imaging were useful to evaluate not only the topographic localization of the masses of extramedullary hematopoiesis, but also their functional status. On CT, masses in the active phase exhibit high density and marked enhancement after i.v. administration of contrast medium; in the remission phase, the masses are hypodense, due to fat substitution, and unenhanced. On MR images, the active phase is characterized by a relatively low signal in both T1 and T2, while in the remission phase high signal is observed in both T1 and T2. A sign is seen on MR images which is considered as pathognomonic: a peripheral ring with high signal. The use of CT and MR imaging allows detailed information on the evolution of the hemolytic disease to be obtained. These pieces of information cannot be obtained with conventional radiology, which allows, at any rate, the correct diagnosis to be made.


[The diagnostic imaging of intrathoracic extramedullary hematopoiesis].

Extramedullary hematopoiesis is a rare finding. It represents a compensatory mechanism capable of assuring and keeping sufficient erythrogenesis. The distribution of the main locations of extramedullary hematopoiesis was observed in different organs and apparatuses. According to their experience, the authors investigated the potentials and limitations of conventional radiology, of CT and MR Imaging, to diagnose intrathoracic extramedullary hematopoiesis in the posterior mediastinum. While stressing the value of clinical and anamnestic data and of conventional radiology, the authors emphasize the leading role of CT and MR imaging. As a matter of fact, the latter is the method of choice, thanks to higher contrast resolution and to its multiplanar and multiparameter capabilities, in the study of space-occupying lesions in the costo-vertebral region. On the other hand, MR Imaging fails to detect calcic areas in paravertebral masses; moreover, the exhaustive and morphostructural analysis of bone segments, ribs and vertebrae, is allowed only by CT.


[Strecker vascular prostheses. The median- and long-term results].

Between September 1989 and October 1991, 37 patients were treated with percutaneous transluminal angioplasty (PTA) and the insertion of a Strecker stent. The patients--35 men and 2 women, mean age 61 years, range 41-47--had 39 lesions in 39 arteries--30 iliac arteries, 8 femoral arteries and 1 popliteal artery. The lesions included 19 dissections after PTA (48%), 13 residual stenoses > 30% after PTA (34%), 7 restenoses (18%) and 4 total occlusions (10%). The stents were successfully inserted in 37/39 cases (95%). Complications occurred in 4 patients: 2 acute thromboses (resolved with local infusion of urokinase), 1 distal embolization and 1 pseudoaneurysm. Distal embolization, despite aspiration and local fibrinolysis, required leg amputation after about 1 month. The max follow-up period was 2 years (average 15 months): patency was 97% at 1 and 3 months, 100% at 6 and 12 months, 95% at 18 months and 100% at 24 months. Total patency was 85% at 24 months. Four patients were lost to follow-up, and 1 patient died. Four stents failed: 2 of them at 1 and 3 months, and surgery was performed, and 2 at 18 months. Intimal hyperplasia of minimum grade occurred in 2 vessels. There was no evidence of stent migration. The authors believe that the placement of Strecker stents is a valuable approach to the treatment of PTA complications.


[The percutaneous treatment of the urological complications following kidney transplantation].

Renal transplantation is considered the treatment of choice in most cases of renal failure; the urologic complication rate ranges 1 to 10% in different surveys. This work was aimed at evaluating the application and results of interventional radiology in these cases. Since 1983, 24 patients (20 males and 4 females) whose age ranged from 18 to 63 years (mean age: 42 years) have been submitted to percutaneous maneuvers in our department. Thirty-four complications were treated: 14 stenoses, 11 fistulas, 7 urinomas and 2 transient obstructions. Complete success was obtained in 15/24 patients (62.5%), while 7/24 patients (29.16%) underwent reoperation and in 2/24 cases (8.34%) a definitive pyelostomy catheter was inserted. In 7 stenosis cases ureteroplasty was successfully performed and a double-J endoprosthesis inserted; the follow-up results (5-21 months) were satisfying in all cases. The only complication was one case of endoperitoneal hematoma. Considering the good results obtained, the low morbidity and mortality and the low cost, percutaneous maneuvers must be considered the treatment of choice in the urologic complications of renal transplants. When the percutaneous treatment of the main lesion fails, pyelostomy does nonetheless allow the drainage of urinary collections, the maintenance of renal function and the improvement of local and general conditions, which makes it easier to reoperate under elective conditions.


[Percutaneous transjugular intrahepatic portosystemic shunt (TIPS). The preliminary experience and proposal of a new method].

A new interventional procedure employing metallic stents has been recently suggested to perform percutaneous portosystemic shunts in the treatment of variceal bleeding in portal hypertension; the technique is called TIPSS (transjugular intrahepatic portosystemic stent shunt). This percutaneous treatment presents several advantages over surgery: the shunt diameter can be calibrated according to the degree of portal hypertension; moreover, TIPSS can be performed in patients waiting for liver transplantation because it does not alter the vascular anatomy of liver. The original technique employed transhepatic portography. In this paper the authors report on their personal experience and present their series of 4 patients with portal hypertension and variceal bleeding, in whom TIPSS was performed utilizing noninvasive US guidance. Variceal bleeding was successfully treated in all patients and variceal distension was also obtained.


[Percutaneous gastrostomy].

Percutaneous gastrostomy was developed over the last years as an alternative method to surgical and endoscopic procedures, either for enteral feeding or for drainage of secretions or fluid collections communicating with the upper gastrointestinal (GI) tract. January 1990 through January 1992, 15 percutaneous gastrostomies and 2 percutaneous jejunostomies were performed at the Gastroenterologic Radiology Division of INT, Milan, Italy. The catheters were always inserted under local anesthesia, generally using special gastrostomy sets. Catheter insertion was possible in all the patients who underwent the procedure: in 12 cases gastrostomy allowed enteral feeding till the patients died and in 1 case the catheter is still working. In 2 cases the procedure was performed for drainage of gastroenteric secretions and the catheter was left in situ as a definitive palliation. In 1 patient the catheter was removed after draining a collection due to an anastomotic fistula. No major complications were observed in 17 procedures. In our experience, the indication according to which percutaneous gastrostomies and jejunostomies were performed for enteral feeding was always affected by the presence of a stenosis, in the upper GI tract. Other indications to the procedure, for enteral feeding, are functional swallowing disorders. Finally, it must be emphasized that when tight stenoses of the upper GI tract are present, percutaneous gastrostomy is the sole alternative to surgery.


[The echographic aspects of prostatic carcinoma before and after radiation treatment].

The authors evaluated the US patterns of 50 prostatic carcinomas before and after radiation therapy, analyzing the correlation of US patterns with histologic (bioptic) findings and with treatment outcome. Before radiation therapy, 28 tumors were hypoechoic, 8 were isoechoic and 14 mixed. In 18 of 28 hypoechoic carcinomas, the lesion showed a progressive increase in echogenicity, becoming completely isoechoic 9-18 months after the end of treatment. In this group of patients the final response to treatment was complete in 17 cases and partial in 1; during the follow-up (24-90 months, mean 48 months) neither local recurrences nor distant metastases were observed. In 10 of 28 hypoechoic carcinomas, a hypoechoic area of variable size was still clearly recognizable within the lesion after a minimum period of 18 months since the end of treatment. Nine of these patients underwent histology and persistent carcinomas were found in 8 of them; one patient developed distant metastases. In the group of isoechoic and mixed carcinomas, no significant differences were observed in the US patterns relative to treatment outcome. Persistent prostatic carcinoma after radiation therapy seems not to affect its US pattern. If the tumor is hypoechoic before treatment, the persistence of a hypoechoic area within the lesion 18 months after the end of treatment must be regarded as a possible therapeutic failure and histologically verified. On the contrary, the evolution of the lesion toward isoechogenicity is usually related to a favorable outcome. If the tumor is isoechoic or mixed before treatment, a reliable US evaluation is not possible and the correct assessment of the response to treatment can only be made with multiple biopsies.


[The evaluation of the performance of a new-concept screen-film system].

Aim of this work is to show the results of the evaluation of the sensitometric properties of a new Du Pont anti cross-over radiographic film system called Ultra Vision, based on a new film and different YTaO4 undoped screens whose emission is centered at about 335 nm. Fog, contrast, latitude, sensitivity, noise and resolution were tested: the MTFs were obtained by exposing a standard resolution pattern and using the "zero"-frequency step as a knife edge. The image of this knife edge was scanned with a microdensitometer with a 20 microns slit. The results (at 70 kVp with 2.5 mm Al and 2.5 mm Cu total filtration), compared with those of Du Pont conventional radiographic screen-film systems Cronex 10 S/Quanta, show that the new system significantly increases contrast, sensitivity and resolution and will consequently improve, in the clinical use, radiographic image quality.


[Clinical and diagnostic characteristics of bladder instability in urinary incontinence in the elderly].

Urinary incontinence is a common disease in elderly people, and the vesical instability is the most frequent cause. A prospective clinical study was done in elderly subjects with established urinary incontinence, produced by vesical instability, to find out if the analysis of several clinical parameters (general and urinary) together with the physical exam, are enough to establish a definitive diagnosis of vesical instability. The most characteristic urinary symptoms were urge incontinence (100%) and diurnal frequency (72%). Physical exam was normal in most patients. Our findings show that the clinical history and physical exam alone do not provide enough information to adequately characterize vesical instability, so, besides these parameters, an urodynamic study is needed to establish the originating mechanism of the urinary incontinence.


[Hemodynamic impact of tension ascites and evacuatory paracentesis].

Cardiac function is studied with regular hemodynamic determinations and 2D-doppler echocardiography, in 22 patients with massive ascites. Patients were divided in two groups: 1. Hepatic cirrhosis (n = 12) and 2. Peritoneal carcinomatosis (n = 10). Patients with carcinomatosis showed lowered heart-beat volume, cardiac output, ventricular work and ejection fraction in comparison with cirrhotic patients. In cirrhotic patients the hemodynamic study was done before and after an evacuatory paracentesis, following which an improvement in cardiac function was shown, with significant increments in heart-beat volume, cardiac output, ventricular work, and ejection fraction. 42% of the cirrhotic patients showed an hyperdynamic circulatory status in the baseline study, but after paracentesis this hyperkinetic status was present in 100% of the patients. It is suggested that tension ascites influences negatively in cardiac function because it difficult the venous return. This depression in the ventricular function is more obvious in patients with carcinomas that in cirrhotic patients due to the fact that the former do not have a previous circulatory status.


[Significance of apolipoproteins A and B and the remaining lipid fractions as indicators of protein-calorie malnutrition in the elderly].

Effects of calorie/protein malnourishment have been studied on plasma concentrations of cholesterol, triglycerides, HDL-C, LDL-C and apolipoproteins A and B, in institutionalized elderly people, 53 males and 62 females, of whom 19 females and 12 males were malnourished. In malnourished patients, total cholesterol and LDL-C were significantly lower both in males and in females, but HDL-C was lower only in females. No significant differences in plasma triglycerides were found between the control and the malnourished groups. Apolipoprotein A showed no significant changes on malnourished males, but did show a significant lowering in malnourished females. On the opposite, apolipoprotein B was lower in males than in females. The lowering in cholesterol in malnourished patients leads us to think that this could be a early predictor of nutritional risk in the elderly.


[Hereditary hemorrhagic telangiectasia at an internal medicine service: study of 12 patients].

Hereditary hemorrhagic telangiectasia (HHT) is a hereditary dominant autosoma clinical entity characterized by repeated hemorrhages (being epistaxis the more frequent) and telangiectasia in skin, mucosa and internal organs. Incidence in Europe is 1,2 per 100,000 pop. We discuss the experience of an Internal Medicine Department (Arnau de Vilanova Hospital), during 10 years, in which 12 patients were diagnosed. With the aim to provide more information about this rare disease. There was no predominant sex and the age of onset was very variable. All patients referred at admission past history of hemorrhages (either the patient him/herself or some relative), or were suffering it at admission. Except one patient, all of them showed telangiectasias in skin and mucosa. In five of them telangiectaias were found in upper gastrointestinal tract, in two there were localized on the tracheobronchial tree and one patient had teleangiectasia in liver. Three patients were diagnosed of pulmonary arteriovenous fistula (PAVF). The clinical, diagnostic and therapeutic aspects of this disease are reviewed.


[Candida laryngitis and HIV infection: description of 4 cases].

Candidiasic laryngitis is a very rare Candida spp infection of mucosa, appearing typically in immunosuppressed patients, mainly in patients with neoplasia, and, recently, in patients with Human Immunodeficiency Virus (VIH) infection. We present four cases of candidiasic laryngitis and HIV infection, as well as the clinical description and evolution of said cases after treatment with fluconazole. We review, as well, the cases published on the scientific literature. We maintain that in each HIV infected patient, with or without oral candidiasis, who shows dysphonia, candidiasic laryngitis should be ruled out.


[Spinal epidural abscess. 8 years' experience].

We present four cases of spinal epidural abscess diagnosed in Clinica Puerta de Hierro between 1982 and 1990. In three cases the localization was thoracic and in one it was lumbar. Fever and vertebral pain were the more constant clinical symptoms. Lumbar punction showed findings in Cerebro-Spinal Fluid compatible with a parameningeal inflammation focus in the three cases it was performed. Diagnosis was established with myelography or Computerized Axial Tomography. Treatment in two cases was laminectomy and systemic antibiotics: and only antibiotics in the other two cases. Evolution was favorable in the patients who underwent surgery, but the patients treated conservatively had a fatal outcome.


[Immunoblastic lymphoma as expression of the final phase of IgA multiple myeloma].

We present the case of a patient diagnosed of IgA multiple myeloma who, four months after being diagnosed and after four cycles with VCAP with good response, showed high fever and constitutional syndrome; multiple subcutaneous nodules appeared during his hospitalization. Biopsy of the bone marrow, and of one of the nodules showed an immunoblastic lymphoma. Even with treatment the patient died due to a pneumonia and a digestive hemorrhage.


[Adverse drug reactions: Naranjo's and Venulet's algorithms].

Prospective evaluation of adverse drug experiences (ADE) in patients admitted in the Respiratory Section of a General Hospital. 32 ADE's were collected (14.6%). Mean age and stay-length were longer in ADE group but with no statistical significance. Theophyllines, beta-mimetics and antibiotics were the more frequent responsibilities of ADE's. ADE's class more frequently reported was epigastralgia-nausea in 40.6%, followed by dermic disorders in 18.75%. No deaths were attributed to ADE's ans only 9 required an specific treatment. Using Naranjo's and Venulet's algorithms we have found them as non-comparable tests.


[Long-term results of surgical treatment of soft tissue retroperitoneal sarcomas].

Soft-Tissue Retroperitoneal Sarcomas (STRP) are rare tumors. Late diagnostic and extreme technical difficulties to obtain total resection with margins free of tumor, are associated to a high relapse rate. Eighteen patients with STRP were retrospectively reviewed, evaluating: Clinical onset, histology, treatment-type performed, mortality and survival rate. Total resection was performed in eleven patients (61%), with inclusion of neighbor organs or structures in five of them (45%). In one case partial exeresis associated with left hemicolectomy was done, and only biopsy was performed in six cases. After total exeresis, seven patients showed local relapse (64%) and four of these patients (57%) underwent surgery again. Global surgery mortality was one patient. Survival at five years in resected patients was 57%. In patients with biopsy only, mean survival was 16.6 months, patients with total or partial resection, survival was 79.1 months. An aggressive surgical approach, with tumor total exeresis and a block resection of neighbor affected organs or structures, is the best alternative in the treatment of STRP.


[Prognostic value of anti-RNP/Sm and anti-Ro/La antibodies in lupus nephropathy].

With the aim to analyze the prognostic value of anti-RNP/Sm and anti-Ro/La antibodies (Ab) in lupus nephropathy, we have studied through Contraimmunoelectrophoresis (CIE) and Immunoblotting (IB) the serum of 63 patients diagnosed of systemic lupus erythematosus. Mean age was 36.5 years (15-71) and 90% were females. We have classified the patients into three subgroups: I, 25 patients without nephropathy; II, 26 patients with evidence of nephropathy (persistent proteinuria and/or microhematuria) and normal renal function; and III, 12 patients with renal failure (servu creatinine > 1.5 mg/dl). 21 patients had kidney biopsy. IB allows to identify a higher number of positive serum, specially in the case of anti-RNP (7.9% CIE vs 28.5% IB) and anti-Sm antibodies (6.3% vs 30.1%). Prevalence of anti-RNP Ab is lower in subgroup III (32% I vs 34% II vs 8% III) (p > 0.05). Anti-Sm Ab are more frequent in group II and are not associated with renal failure (16% vs 54% vs 8%) (p > 0.05). Anti-Ro Ab are related with the absence of nephropathy (52% vs 15% vs 0%) (p < 0.05). We conclude that IB is more sensitive than CIE in the detection of these Ab and its use in Systemic Lupus Erythematosus permits to identify patient subgroups with lesser risk to develop renal failure. Even though our data are preliminary, we suggest that the detection of anti-RNP/Sm and/or anti-Ro/La antibodies are a good prognostic factor in lupus nephropathy.


[Treatment of colonic cancer with laser (Nd-YAG). Our initial experience].

Laser-therapy represents an acceptable alternative in the palliative treatment of colon cancer. We have treated 25 patients with this pathology, 10 with obstructive tumor, which impeded the insertion of the endoscope, and 15 non-obstructive tumors. Higher technical difficulties on the former, together with a worse clinical situation, due to the fact that the tumor was more invasive, produce a more discrete result and with a higher risk of complications (one patient had a perforation and other an obstructive stenosis after two months of treatment) in comparison with the group of patients with non-obstructive tumors. However the treatment improved their quality of life with the recovery of their intestinal function. Among patients with non-obstructive tumors of the colonic light, prolonged survival (mean 6.8 months) was reached by 73.3% of patients belonging to this group; disappearing after treatment even the endoscopic view of the tumor in 33.3% of the patients.


[Castleman's disease. A multifactorial study].

A case of Castleman's disease (hialino-vascular subtype) in a female patient 15-years-old is considered. Clinically there were isolated lymphadenopathies which relapsed after surgery and absence of general syndrome. Histoimmunological and electron microscopic studies were performed as DNA rearrangement and cytogenetics in order to exclude genetic abnormalities and monoclonality of this disorder. The role of follicular dendritic component in discussed.


[Dermatomyositis, Sjögren's syndrome and vasculitis: an infrequent overlapping connective disease].

A dermatomyositis case with Sjögren's syndrome, Leucocytoclastic vasculitis, and sclerodermiform features is presented. This is a peculiar over lapping connectivepathy in which clinical features of three multisystemic diseases are together. The association of dermatomyositis with Sjögren's syndrome is very rare.


[T-lymphomas with splenic presentation].

Three cases of lymphomas with splenomegaly onset, without peripheric adenopathies, which required laparotomy to be diagnosed, are discussed. One of the cases was a primary splenic lymphoma and the other two were associated with reactive hemophagocytosis. Other malign lymphoproliferative processes of predominant splenic onset are discussed.


[Vascular manifestations in 30 cases of Behçet's disease].

Vascular manifestations on Behçet's disease (BD) vary from 25 to 65% according to different series. Affects both arteries as veins, but superficial thrombophlebitis is the most frequent disorder. Disorders with higher morbidity like deep venous thrombosis, and arterial aneurisms can appear, even in the lungs. In our series of 30 patients we found an incidence of 46% of vascular manifestations, mainly (92%) superficial thrombophlebitis. We highlight the presence of a femoral aneurism, which was resected, and discuss its evolution and response to treatment with prednisone and cyclophosphamide. We review in-depth the vascular manifestations in the Spanish and International scientific literature, paying special interest to aneurism dilatations.


[Regression of coronary arteriosclerosis with hypolipidemic treatment, myth or reality?].

Coronary atherosclerosis regression with hypolipemiant treatment is a well known fact in the animal model since years ago. In humans, during these last years, several clinical trials have been performed to ellucidate the truth to this fact. All of these clinical trials have in common the evolutive study of the coronary lesions with angiographies, in patients following treatment with diet, surgery or drugs, to reduce plasmatic cholesterol. Clinical, analytical and angiographic results of said studies are reviewed. We conclude that the bigger the lowering in plasmatic cholesterol levels, smaller is the progression of these coronary lesions and more probable is finding patients with partial regression of the lesions.


[Application of bidimensional echocardiography in the diagnosis of ventricular septal defect].

Between 1985-1990 we studied by means of two-dimensional echocardiography 286 patients with isolated ventricular septal defect (VSD). A hundred and sixty three being male and 123 female, as a mean age of 5 +/- 3 months. Sixty two cases (22.3%) reveales associated anomalies and in other 63 (22.4%) there was in the evolution an aneurysm of the septum membranous. The projections used were apical 4-chamber, with or without aortic root; parasternal long-short axis of great arterias or at ventricular level; subcostal 4-chamber; right oblique outlet right outflow tract and left oblique outlet left and right outflow tracts. Patients with VSD smaller than 3 mm were excluded. Perimembranous defects, 189 cases (66%), were more frequent than muscular, 91 31.8%), and subarterial defects, 6 (2.1%). Only 19 (9 apical muscular, 6 perimembranous outlet and 4 perimembranous trabecular) were initially misclassified. The diameter of the VSD was large in subarterial (0.85 +/- 0.1 cm) and perimembranous outlet VSD (0.75 +/- 0.5 cm) compared with the rest. Each group of defects was more easily shown by one particular projection except trabecular muscular defect. In conclusion, we are able to state that two-dimensional echocardiography enables us to discover the size and situation of isolated ventricular defects.


[Endomyocardial biopsy in heart transplantation].

From October 1984 to June 1991, 1,549 endomyocardial biopsies (EMB) were performed on 122 patients submitted to a Cardiac Transplant procedure (CT) at the Hospital Puerta de Hierro in Madrid. All biopsies were performed with the long sheath technique and the King bioptome. A total of 8,707 specimens were obtained, of which 7,311 (83.97%) were considered adequate for pathological examination. We did not find significant differences between the internal jugular (83.21%) and the femoral vein (84.82%) approaches. About 20% of the samples were not adequate for pathological evaluation after the fifth procedure performed on the same patient. There has been no deaths in our group. One patient (0.06%) had right ventricular perforation with tamponade that required surgical treatment. Two patients (2.98%) presented coronary fistulae related to EMB. The percent of other minor complications was less than 0.5%. EMB is mandatory for the control of rejection in the first year after cardiac transplantation, and has shown to be a reliable and safe method in experienced hands.


[Changes in diastolic function in heart rejection: role of Doppler echocardiography].

In acute cardiac rejection, left ventricular diastolic function is altered. To study these abnormalities and their utility in cardiac allograft rejection, we studied 56 cardiac transplant recipients. All patients were assessed with endomyocardial biopsy and Doppler echocardiography done in the same day. A total of 163 Doppler studies were recollected. Cardiac transplant recipients were excluded during the early 6 weeks postoperative period. Totally, 100 biopsies were normal, 48 positive for mild rejection (Billingham Gde I-II) and 15 positive for moderate or severe rejection (Billingham Gde III-IV). Compared to negative biopsies, during acute rejection left ventricular wald thickness significantly increased (p < 0.05); isovolumic relaxation period and pressure half-time significantly decreased (p < 0.05, p < 0.001 respectively). Nevertheless, increase in peak early mitral flow velocity was only significantly associated with severe rejection (p < 0.001). Correlating only progressive shortening of isovolumic relaxation period parameter in the diagnosis of graft rejection, we forward a high sensibility (85%) and low specificity (57%). Thus, Doppler echocardiographic evaluation of left ventricular diastolic function provides a non-invasive tool for early detection of acute rejection monitoring after the early postoperative period.


[Atrioventricular and ventriculoarterial discordance (corrected transposition of the great vessels). Diagnosis with bidimensional echocardiography].

We present 15 patients with atrioventricular and ventriculoarterial discordance diagnosed with two-dimensional echocardiography from January 1973 to June 1991. The 15 had situs solitus and six dextrocardia. A different level of insertion of the atrioventricular valves worth from 0.77 +/- 0.3 cm, was observed in all the cases which didn't perimembranous inlet ventricular septal defect. Ten patients, presented septal insertion of one of the chords of the left atrioventricular valve, while, this insertion wasn't observed in the right atrioventricular valve. The ventricular morphology and trabeculation, permitted the identification of both ventricles in all the cases. The subxifoidea view resulted in being fundamental, for the examination of the ventriculoarterial connections. Ten cases (66.6%) had an obstruction in the pulmonary outflow tract (6 in the valve and 4 in subvalvular area) and nine (60%) ventricular septal defect (7 perimembranous and 2 muscular). We believe that the two-dimensional echocardiography gives enough information to arrive at the correct diagnosis of this cardiac malformation and of the associated anomalies. This information can be completed with the use of the color-flow Doppler.


[Aortic atresia with situs inversus].

We report a case of mitro-aortic atresia with situs inversus. The patient was studied with two-dimensional echocardiography and the diagnosis was confirmed in the necropsy. Our newborn infant is the second case reported with this abnormality and the first in our country.


[Contusion and post-traumatic hematoma of the interventricular septum. Report of a case].

Severe thoracic trauma is a common cause of admission in Intensive Care Units; then heart injury is not a rare finding. We present a case of post-traumatic interventricular dissection and ventricular aneurysm secondary to thoracic trauma caused by traffic accident. We think that ventricular septum injury is a rare finding after chest trauma. Two-dimensional echo-cardiography is an essential procedure in the diagnosis of traumatic heart injury.


[Anomalous origin of left coronary artery in pulmonary artery].

We report 2 infants aged 6 months and one year with an anomalous left coronary artery origin treated surgically at our centre with direct aortic reimplantation of the anomalous coronary. Evolution has been satisfactory, with a great improvement of ventricular function. The mitral incompetence and congestive heart failure have disappeared and myocardic perfusion electrocardiographic patterns were corrected. Because of the unfavorable natural course of the disease and the improvement in techniques of coronary revascularization in infants we recommend an early surgical treatment as soon as it be diagnosed. We consider that the most adequate surgical treatment is the direct aortic reimplantation of the anomalous coronary artery.


[Cardiovascular surgery in Spain in 1991. Registry of operations of the Spanish Society of Cardiovascular Surgery (SECCV)].

The Spanish Society of Cardiovascular Surgery has sent a questionnaire to all 37 cardiovascular surgical groups to know the number and type of cardiovascular operations carried out in our country during 1991. The questionnaire was answered by 36 out of 37. In the year 1991, 21,771 cardiovascular patients have been operated upon and 10,913 interventions with extracorporeal circulation have been carried out: 42.4% in valvular disease, 37.2% in coronary and 11.2% in congenital. The number of operations was 5,415 for vascular disease, 4,627 for valvular, 3,168 for coronary, 1,896 for congenital and 3,741 for pacemaker implantation. The total number of operations in 1991 comparing to those performed during 1988 is similar; but the number of open heart operation and the number of these per cardiac unit and per million population during 1991 have increased 20.5, 13.9 and 24.3% respectively. Coronary and valvular operations have also increased 11 and 27% respectively, as well as the number of pacemaker implanted (30%). The number of congenital cases remains the same and the number of vascular operations has decreased by 7.9%.


[Doppler echocardiography assessment of cardiac abnormalities in parenteral drug addicts].

We studied by Echocardiographic-Doppler 114 consecutive intravenous drugs addicts (IVDA); 91 were positive human immunodeficiency virus (HIV+) and 23 negatives. We classified them in five groups; beginning the negative HIV as group 0, and groups I to IV stratified according the Central Disease Control (CDC) classification. We compared the cardiac abnormalities founded between themselves and a control group presumed healthy persons of similar age. The cardiac cavities dimensions showed a statistic significant increased left ventricular end-systolic and diastolic diameters, right ventricular diameter, posterior wall and interventricular septum thickness and aortic root diameter compared with the control group; but all were in the normal range for age. The left ventricular fractional shortening was statistically different from control group related the other groups, and the group IV related other. The existence and severity of pericardial effusions were directly related to the illness stage. We founded moderate pericardial effusions in 25% patients in the 0 to III groups, increasing until 50% in the group IV. The presence of valvular vegetations, nearly 30% in our series, ought to the IVDA. We did not found relationship between the severity of valvular incompetence and the illness stage. We recorded a excellent correlation between the ratio T4/T8 lymphocytes with the progress of illness and the existence and severity of cardiac abnormalities.