Autoxidation and yellowing of methyl linolenate.

The autoxidation of fatty esters of linseed oil is studied extensively, and the products formed from these reactions are identified. The mechanism suggested for autoxidation, helps to understand fat deterioration resulting in offensive odours and flavours, and to develop new antioxidants to prevent this decomposition. The oxidation following oxidative copolymerization should be investigated in order to understand and to develop new methodology to prevent yellowing. Although the yellowing of indoor oil paints could be prevented to an extent, no compound is known to completely inhibit this process nor has the cause for this yellow colouration been isolated, leaving the doors wide open for further investigation.


Cigarette smoking reduces human salivary eicosanoids.

The effect of cigarette smoking on salivary eicosanoid levels was investigated in 10 smoker and 10 non-smoker volunteers. The smokers consumed an average of 20 cigarettes/day for the past 5 years or longer. The smoking status was validated by salivary cotinine level. Eicosanoids were extracted from saliva with ethanol, and the radioimmunoassay was performed to determine the concentrations of four major eicosanoids, i.e. prostaglandin E2 (PGE2), PGF2 alpha, 6-sulphidopeptide-containing leukotrienes (LTs) and 12-hydroxyeicosatetraenoic acid (12-HETE). The levels of PGE2, PGF2 alpha, and LTs were significantly lower in the saliva of smokers as compared to that of the non-smokers (1.74 +/- 0.32 vs 2.41 +/- 0.64, p = 0.006; 0.36 +/- 0.12 vs 0.54 +/- 0.18, p = 0.04; 2.24 +/- 0.96 vs 4.92 +/- 1.29, p = 0.006; mean +/- SD, ng/ml saliva). No significant differences were found in the levels of 12-HETE between the two groups. The results suggest that cigarette smoking reduces the concentrations of both the cyclooxygenase and 5-lipoxygenase products in saliva.


Brain tissue injury and blood-brain barrier opening induced by injection of LGE2 or PGE2.

The hypothesis that the accumulation of prostaglandin (PG)E2 during reperfusion of severely ischemic tissue contributes to a breakdown in the blood-brain barrier (BBB) was expanded to include a parallel role for levuglandins(LGs), gamma-ketoaldehydes produced by rearrangement of PGH2. LGE2 was shown to be more potent than PGE2 in causing breakdown of the BBB when injected intrahemispherically. Brain tissue necrosis was clearly evident with total doses of levuglandin as low as 100 nmole.


Amniotic fluid embolism and leukotrienes--the role of amniotic fluid surfactant in leukotriene production.

Surfactant rich lipid (lipid) was extracted from cell free 10,000 x g pellets of amniotic fluid. White blood cells (WBC) were isolated from human donors. 36 x 10(7) WBC and 5 g rabbit lung were incubated with pretreated lipid or dipalmitoyl lecithin (lecithin). Leukotrienes (LTs) were identified by high performance liquid chromatography (HPLC) and bioassay, and quantified by radioimmunoassay. Peaks of LTC4 and LTD4 on HPLC and guinea-pig ileum contraction could be identified in lipid and lecithin groups, but not in the control group. LTC4 production by lipid and lecithin groups was significantly higher than that by the control group. An involvement of amniotic fluid surfactant in leukotriene production is suggested.


Alteration of platelet activating factor (PAF) metabolism in rat pulmonary alveolar macrophages and plasma by cigarette smoking.

The pathophysiological role of platelet activating factor (PAF) in smoking-induced disorders was examined in rats exposed daily to smoke for 10, 18 and 26 weeks. The concentration of PAF in bronchoalveolar lavage fluid and the activities of PAF biosynthetic and catabolic enzymes in alveolar macrophages and in plasma were determined. The concentration of PAF in lavage fluid of the smoke-exposed group was significantly lower than that in the sham group for each duration of smoke exposure. The PAF biosynthetic enzyme, acetyl transferase, activity in alveolar macrophages of smoked group was less than that in the sham group although the difference was not statistically significant. PAF catabolic enzyme, acetyl hydrolase, activities in alveolar macrophages and in plasma were all significantly higher in every smoked group than in the sham group. These data indicate that cigarette smoking alters PAF metabolism in the respiratory tract and in plasma and such an alteration may contribute, at least in part, to smoking induced cardiopulmonary disorders.


The influence of fish oil supplementation on plasma lipoproteins and arterial lipids in vervet monkeys with established atherosclerosis.

There is controversy about whether supplementing diets with marine fish oil can regress, promote or prevent atherosclerosis. Therefore the effects of an Atlantic pilchard oil (FO) supplement and dietary change were measured in a proven atherosclerosis model. Vervet or African Green monkeys were fed an atherogenic diet (AD) for long enough to ensure progression before treatments started. Matched groups were then treated for 20 months, either by adding FO to the AD (AD/FO), or by changing to a therapeutic diet with FO (TD/FO). Control treatments consisted of supplementing with sunflower oil (SO) instead of FO, so that treatments were AD/SO and TD/SO. The same total polyunsaturates were supplied by the FO and SO and the dose of FO was realistic (2.5% of total energy). A reference group (R) received the TD with no oil supplements. Supplementing with FO did not change the concentrations of total, low or high density lipoprotein cholesterol in plasma. After The AD/FO the intimas of aortas contained more total (p < or = 0.001), free (p < or = 0.05) and esterified (p < or = 0.05) cholesterol, total phospholipid (p < or = 0.01) and sphingomyelin (p < or = 0.05) than after the AD/SO. After FO supplementation eicosapentaenoic acid was significantly higher and arachidonic acid significantly lower in the plasma and aorta intima phosphatidylcholine. None of these changes was anti-atherogenic in terms of atherosclerosis measured in the same individuals (1). Nor did FO increase the efficacy of the TD.


On the role of 'in vivo' injected progesterone and of the 'in vitro' presence of oxytocin, modulating Ca2+ uptake by the rat uteri from spayed animals and as controllers of the production of arachidonic acid metabolism.

We attempted to explore possible mechanism(s) subserving the influence of oxytocin (O) and of progesterone (P) in the isolated rat uterus studying the action of these hormones on: the synthesis and release of prostaglandins (PGs), the metabolism of labelled arachidonic acid and the uptake of Ca2+ by the tissue from ovariectomized animals. The experiments were done with uterine preparations isolated from spayed rats treated or not with P prior to sacrifice and afterward incubated or not with O 'in vitro'. While uterine strips from untreated spayed rat uterus exhibited a basal release into the incubating medium of approximately the same amounts of PGF2 alpha, and PGE2, the 'in vitro' addition of O (50 mU/ml) increased significantly (p < 0.05) the output of PGF2 alpha without changing the release of PGE2. In tissue from rats injected with P prior to sacrifice the output of PGF2 alpha rose significantly (p < 0.01) as it did after the addition of O to preparations obtained from spayed rats treated with P in comparison to findings in uteri from spayed rats but not in comparison to uteri from spayed rats treated with P alone. Moreover, the 'in vitro' addition of O (50 mU/ml) only increased the formation of PGF2 alpha (p < 0.05) and of 5-HETE (p < 0.05); nevertheless the administration of P to spayed rats diminished significantly (p < 0.05) the formation of 6-keto-PGF1 alpha from uteri, but increased that of PGF2 alpha (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Sex and dietary fat modulate hepatic prostaglandin F2 alpha in F344/N rats.

The study was designed to determine whether sex and fat calories altered hepatic prostaglandin (PG) F2 alpha status; a factor which may reflect susceptibility to cancer development. For 4 weeks, groups of 8 male and 8 female F344/N rats were fed diets with 9% of energy (en%) from linoleate and 15.5, 20, 30 or 40 en% fat. Females had greater hepatic stearate, arachidonate and PGF2 alpha whereas males had greater hepatic myristate, palmitate and oleate. Females also had greater plasma stearate levels. Greater hepatic arachidonate may have stimulated PG production in females. Hepatic oleate increased and hepatic palmitate decreased with increasing en% fat (p < 0.05). Hepatic stearate was greater and hepatic linoleate less when 40 en% fat was fed compared with other levels of dietary fat (p < 0.05). Plasma oleate was greater at 30 or 40 en% fat than at lower levels of fat, whereas plasma linoleate was less at 40 en% than at 15.5% en% fat. The ability of a 30 en% fat diet, containing equal proportions of linoleate and oleate, to suppress hepatic PG production may be related to the effects of dietary fat content and composition on plasma fatty acid profiles. Because suppressed PG production has been linked with suppression of cancer development, dietary recommendations to consume 30 en% fat with a P:M ratio of 1:1 may be cancer-protective.


Does a HDL injection reduce the development of serum hyperlipidemia and progression of fatty streaks in cholesterol fed rabbits?

The influences of homologous (rabbit) or heterologous (human) high density lipoprotein (HDL) on the development of serum hyperlipidemia and progression of fatty streaks were studied in cholesterol fed rabbits. Three groups of New Zealand rabbits were fed a 0.5% cholesterol rich diet for 8 weeks. Additionally into these animals the following solutions were injected intravenously two times per week: group 1 (control): saline; group 2: human HDL dissolved in saline; group 3: rabbit HDL dissolved in saline. The animals of group 2 had lower serum cholesterol levels during the dietary period than rabbits of group 1 (p < 0.05) but the surface of intima covered with fatty streaks was the same as in group 1. On the other hand, the serum cholesterol level in rabbits of group 3 was the same as in group 1 during the whole experimental period, but the surface of aorta covered with fatty streaks was significantly lower (p < 0.05) in group 3 than in group 1. The results of this study support the hypothesis of an antiatherogenic action of HDL, which seems to be independent of the influence of HDL on the serum lipids but depends on the source of HDL.


Binding of a thromboxane A2 (TXA2)/prostaglandin H2 (PGH2) receptor antagonist to rabbit and pig heart membrane protein.

This study aimed at testing the hypothesis that the binding sites for TXA2/PGH2 are present and different in the heart as compared to platelets and blood vessels. Kinetic studies on the thromboxane binding to protein of membrane preparations from rabbit and pig hearts were carried out using [125I]-PTA-OH, a potent specific thromboxane receptor antagonist. The following points are stressed: 1. the binding sites to 125I-PTA-OH were shown to be present in the heart membrane whatever the adopted experimental conditions were i.e. the temperature (4 or 30 degrees C) used for incubation the protein fractions under study: either the 105,000 g supernatant or the 200,000 g supernatant of the solubilized pellet (105,000 g) the animal species: rabbit and pig 2. the radioligand binding was rapid, saturable and reversible 3. the kinetically determined Kd's were in the picomolar range--11 and 14 pM for the rabbit and pig heart membrane preparation respectively--instead of the nanomolar range found in other tissues of the nanomolar range found in other tissues--27-39 nM and 2 nM for human platelets and bovine artery endothelial cells respectively- using the same thromboxane receptor antagonist.


NZB/NZW F1 mouse nephritis and immune response are not changed by treatment with a 15-lipoxygenase derivative.

15-HETE is an arachidonic acid derivative issued from the 15 lipoxygenase pathway. This fatty acid possesses immunomodulatory capabilities since it was reported that it generates CD8 + suppressor T-cells either in vitro or ex vivo. The aim of the present report was to study if the suppressive capabilities of 15-HETE were able to influence the onset of the NZB/NZW Fl auto-immune disease. For that purpose we produced 15-HETE and injected the eicosanoid twice a week to NZB/WFI mice for 40 weeks. During the 15-HETE treatment of the animals it was observed an augmentation of the proliferative response of lectin-stimulated splenocytes (at weeks 20 and 30) then the thymidine uptake decreased (at week 40). In fact we observed that among 15-HETE treated mice the evolution of the nephropathy was not changed, the 'glomerular activity score' remained the same for the treated animals compared to controls. On the contrary antinuclear antibodies occurred earlier even if in some experiments the generation of CD8 + cells was demonstrated.


Quantitative association between altered plasma esterified omega-6 fatty acid proportions and psychological stress.

Medical students (MS) tested during the first year of medical school showed both greater stress on the Brief Symptom Inventory and lower plasma proportions of total esterified arachidonic acid (AA, C20:4n-6), and its omega-6 fatty acid (FA) precursor, linoleic acid (C18:2n-6) than control laboratory workers. This association suggests that omega-6 FA metabolism may be affected during stress. Low AA values might result from depletion of plasma stores for immunoregulatory prostenoids formation or from modification of metabolic pathways by cortisol or other cytokine compounds implicated in stress. Values for other major FA and the omega-3 neuronal metabolic substrate, docosahexaenoic acid (DHA, C22:6n-3) were similar between students and controls. The clear preservation of the omega-3 FA pathway suggests their programmed availability for neuronal function during stress. Since plasma FA proportions may affect immune cell membrane function(s), we suggest that altered values of plasma FAs may be an important component of the physiological effects of psychological stress.


Modulation of prostacyclin production by cytokines in vascular endothelial cells.

The data presented in this review clearly show that many different cytokines regulate the synthesis of PGI2 in vascular EC (Tables 1 & 2). Since these agents are synthesized, stored, and/or released from platelets, leukocytes and cells present in the vascular wall (Fig.), they are to be found at sites of vascular injury and may, through their effect on the synthesis of PGI2 and other prostanoids, regulate thrombogenesis and atherogenesis. Despite the mass of detailed data, the picture is still fragmentary. Very little, for instance, is known about the 'orchestral effects' of different combinations of cytokines. In addition, it seems that the regulation of PGI2 synthesis by cytokines varies with the species and with the type of vasculature from which the cells originated. However, discrepancies may also be due to the use of different culture conditions. Moreover, we must remember that the present data are almost exclusively from in vitro studies, and the representativeness of these results in in vivo situations remains to be clarified.


Cancer destruction in vivo through disrupted energy metabolism. Part I. The endogenous mechanism of self-destruction within the malignant cell, and the roles of endotoxin, certain hormones and drugs, and active oxygen in causing cellular injury and death.

Autoxidative cellular injury arises when an intact endogenous mechanism present in cells is triggered by a range of specific stimuli, including endotoxin, stress hormones, hydralazine, L-isoproterenol and certain phenothiazines. The overall changes involve oxygen activation, lipid peroxidation, and the generation of substances which disrupt mitochondrial energy production by uncoupling oxidative phosphorylation. Magnetic resonance spectroscopy has revealed that falls in high-energy phosphate are commonly seen following a variety of therapeutic procedures, including radiation and treatment with cytotoxic agents. Sometimes the energy status of a tumor improves in response to therapy; in these instances tumor regression is due to programmed cell death, termed apoptosis. In the first part of this review the roles played in the development of autoxidative cellular injury by oxygen and its active forms, an endogenous peroxidisable substrate, and an oxygenase are considered and discussed.


Cancer destruction in vivo through disrupted energy metabolism. Part II. Lipid peroxidation and cell death; drug resistance as a consequence of reversible cellular injury.

In the second part of this review of autoxidative cellular injury and death in tumor cells, the presence of saturated or polyunsaturated fatty acids, vitamin E, and free or esterified cholesterol in whole cells and organelles is discussed in the context of enhancing or attenuating lipid peroxidation. The disposition of unsaturation within polyunsaturated fatty acid molecules is critical for tumor promotion, but the situation appears ambivalent with regard to inflicting cellular injury. Increases in lipid peroxidation and phospholipase A2 activity following on from the administration of hormones or non-cytotoxic drugs are considered from the viewpoint of generating hydroperoxyfatty acids and lysophosphatides, both of which disrupt mitochondrial energy production by uncoupling oxidative phosphorylation. The metabolic fate of lysophosphatides is thought to be a crucial factor both in determining whether cancer cells survive or not, and in furnishing protection for surviving cells against subsequent attack. Both energy-dependent and energy-independent mechanisms for acylating lysophosphatides are reviewed. The emergence of an unstable form of drug resistance during the recovery phase is interpreted in terms of the chemical identity of the new acyl groups on the acylated lysophospholipid. Resistance to further free radical challenge can be conferred by the regeneration of phospholipids bearing saturated or monoenoic 2-substituents which are unable to undergo peroxidation.


Cancer destruction in vivo through disrupted energy metabolism. Part III. Spontaneous drug resistance, selectivity of antineoplastic action, and strategies for intensifying tumor injury.

In the concluding section of this review of cancer destruction by disruption of energy metabolism, the cellular mechanism for interfering with energy production is considered in terms of drug resistance arising independently of previous tumor injury. The occurrence of various degrees of damage to cancerous growths as a consequence of secondary shock is interpreted on the basis of elevated levels of stress hormones, including vasopressin, which have earlier been shown to interfere with energy metabolism in a murine sarcoma. Similarly, the indirect action of various antineoplastic procedures can be related to a role for the endocrine system, with particular reference to vasopressin and inappropriate anti-diuretic hormone secretion syndrome. Multiple drug resistance is also discussed, and the mode of action of the topoisomerase inhibitor doxorubicin is critically examined. The basis of selectivity of disruption of energy metabolism by substances such as hydralazine and L-isoproterenol is discussed from the viewpoint of altered activities of antioxidant enzymes in transformed cells, but these considerations alone are not thought to be sufficient to account for the highly specific nature of the antineoplastic action. Conversely, antioxidant enzymes, more especially those concerned with glutathione metabolism, probably play a major role in multiple drug resistance, although in this respect the case of autoxidative cellular injury awaits attention. Theoretical strategies for the intensification of tumor injury include the aim of prolonging the half-lives of lysophosphatides within damaged tissue. Whereas the clinical application of the principle of tumor destruction through selective disruption of energy metabolism is at present compromised for lack of information, the use of phenothiazines as antineoplastic agents is feasible, and awaits serious exploitation. The relative lack of incapacitating side-effects of phenothiazines should provide an attractive change for the clinical oncologist.


Investigation of the possibility of solitary waves in the base stacks of DNA.

The possibility of the existence of solitary waves in DNA is investigated. On the basis of our classical model we do not find such a wave in a polynucleotide, but for a stack of adenine molecules without backbone we observe one. Possible extensions of the model for DNA are discussed. From our results we can conclude, that solitons exist in stacked systems without an additional backbone. At least the degree of freedom which couples a nucleotide base (pair) to the sugar-phosphate backbones (N-C stretching vibration) has to be treated with the help of the quantum equations of motion.


Molecular effects of nitrosamine toxicity.

Nitrosamines are toxic chemical compounds found low in quantity, but widespread in the environment. This work investigated the kinetics of chemical reaction of activated nitrosamines with various organic substrates. The mechanism by which nitrosamines react demonstrates possible pathways in which the toxicity is expressed. Once activated nitrosamines are very reactive. Chemical compounds which can act as nucleophilic substrates may be alkylated by the activated nitrosamines. A broad category of chemical compounds are shown to be suitable substrates for nitrosamine induced alkylation. This large category of substrates suggests a substantial potential for toxic activity in vivo. By investigating the reaction kinetics of activated nitrosamines a greater understanding of their toxic effects may be possible.


The large plasmids found in enterohemorrhagic and enteropathogenic Escherichia coli constitute a related series of transfer-defective Inc F-IIA replicons.

Forty-six of 52 (88.5%) enterohemorrhagic Escherichia coli (EHEC) strains screened carried a "common" plasmid of about 90 kb which encoded sequences homologous to the Inc F-IIA replicon. A similarly high incidence of Inc F-IIA plasmid-containing strains was observed in other groups of diarrheagenic E. coli, but not in random environmental coliform isolates. Enteropathogenic E. coli (EPEC) contain plasmids of similar properties and share a 23-kb DNA fragment with plasmids from EHEC. The common region encodes the F-IIA replication region and sequences homologous to the transfer operon of the Inc F-II plasmid R1. Sequence homology varied between plasmids isolated from different EHEC/EPEC strains with > 80% showing homology to the regions encoding the rep and par genes. Only 5% of plasmids from EHEC strains had intact sequences homologous to the DNA between these two regions, including the oriT site. Some plasmids with an apparently intact tra operon still failed to plaque F-pilus-specific phages. This is consistent with observations that the large plasmids of EHEC and EPEC are phenotypically nonconjugative. These results suggest that the large plasmids of EHEC/EPEC constitute a family of transfer-deficient Inc F-IIA plasmids with varying degrees of deletion in tra function. The evolutionary ramifications of this finding are considered.


Transformation of Acetobacter xylinum with plasmid DNA by electroporation.

Genetic analysis of Acetobacter xylinum, a cellulose-synthesizing bacterium, has been limited by lack of a successful transformation method. Transformation of A. xylinum was attempted using two broad-host-range plasmids (pUCD2 and pRK248) and a variety of transformation methods. Methods using CaCl2, freeze/thaw treatments, and polyethylene glycol were unsuccessful. Transformation of a cellulose-negative strain of A. xylinum with plasmid DNA has been achieved with high-voltage electroporation. Electroporation conditions of 25 microF capacitance, 2.5 kV, 400 ohms resistance, and pulse lengths of 6-8 ms were applied to a cell/DNA mixture in a 0.2-cm cuvette. Plasmid pUCD2 transformed at an efficiency of 10(6)-10(7) transformants/micrograms DNA and pRK248 yielded 10(5) transformants/micrograms DNA. The frequency of transformation increased linearly with increasing DNA concentration, while transformation efficiency remained constant. pUCD2 was recovered from transformants following chloramphenicol amplification and observed by agarose gel electrophoresis. Both plasmids could be reisolated from Escherichia coli after back-transformation with alkaline lysis DNA preparations from Acetobacter transformants. Electro-transformation of A. xylinum with plasmid DNA suggests its potential use for analysis of the A. xylinum genome.


Deletion derivatives of pAgK84 and their use in the analysis of Agrobacterium plasmid functions.

The 47.7-kb plasmid pAgK84, present in Agrobacterium radiobacter strain K84, confers production of a novel, highly specific, antiagrobacterial antibiotic called agrocin 84. Strain K84 is used commercially to biocontrol crown gall caused by agrocin 84-susceptible strains of Agrobacterium tumefaciens. Efficient biocontrol is dependent upon production of agrocin 84 by strain K84. Starting with a derivative of pAgK84 containing a Tn5 insertion, a series of deletion derivatives of the plasmid were isolated. The smallest of these, pJS500, contains about 8 kb of the original agrocin plasmid and localized the replication functions to between 4 and 6 o'clock on the physical map. A smaller derivative, produced by clonal rescue of a Tn5 insertion in the 4 o'clock region, further localized the minimal replication functions to a 1.5-kb region mapping between coordinates 18.1 and 19.6. Analysis of plasmid stability indicated that functions required for maintenance of the plasmid under nonselective conditions are tightly linked to the minimal replication region. This region also encodes incompatibility functions; the deletion derivatives were all incompatible with the wild-type pAgK84. The stability/replication locus of pAgK84 maps just anticlockwise from the Tra region. This region is retained fully in pAgK1026, the directed Tra- derivative of pAgK84 which is now in use as the primary crown gall biocontrol agent in Australia. One of the deletion derivatives, the 15-kb pJS400, was used as a vector to clone the KpnI fragments of an octopine-type Ti plasmid. Traits known to be encoded on these fragments were expressed and properly regulated in Agrobacterium hosts. One clone, encoding the Ti plasmid replication/incompatibility region, was used to cure IncRh1 Ti plasmids from their hosts. This clone also was found to be incompatible with pAtK84b, a large plasmid encoding opine catabolism present in A. radiobacter strain K84. This indicates that the opine catabolic plasmid is closely related to the IncRh1 Ti plasmids.


Promoter probe and shuttle plasmids for Deinococcus radiodurans.

Two improved Deinococcus radiodurans-Escherichia coli shuttle vectors have been constructed. pI3 is a 16-kb plasmid that confers chloramphenicol resistance in D. radiodurans (CmR, cat) and ampicillin resistance in E. coli (ApR) and contains a multiple cloning site that does not interrupt sequences necessary for replication or drug resistance in either host. pI304 is a promoter-probe plasmid that is similar to pI3, but lacks the D. radiodurans promoting sequence for the cat gene, while retaining sequences necessary for replication.


Construction of recA mutants of Acholeplasma laidlawii by insertional inactivation with a homologous DNA fragment.

Mycoplasmas (class Mollicutes) are wall-less prokaryotes phylogenetically related to gram-positive bacteria. This study describes the construction of recA mutants of the mycoplasma Acholeplasma laidlawii. An internal fragment of the recA gene from A. laidlawii was cloned into a plasmid that does not replicate in this organism. When this plasmid construct was used to transform A. laidlawii, it inserted into the chromosome, disrupting the recA gene. The phenotype of the resulting recA mutant was compared to that of wild-type cells and to that of a strain that has a naturally occurring ochre mutation in its recA gene. As found in other bacterial systems, loss of RecA activity resulted in cells deficient in DNA repair.


Nucleotide sequence of the chloramphenicol resistance determinant of the streptococcal plasmid pIP501.

We have sequenced the chloramphenicol resistance determinant (cat) of plasmid pIP501 from Streptococcus agalactiae to investigate its relationship with other cognate cat determinants. Sequence analysis revealed that it exhibits a high degree of similarity with the cat genes of plasmids pC221 and pUB112 from Staphylococcus aureus and pSCS1 from Staphylococcus intermedius. These genes, however, display several differences in their regulatory and coding regions. These results demonstrate that the cat determinant of plasmid pIP501 belongs to the pC221 subgroup of CAT variants.


Monoamine oxidase and cortisol response in depression and schizophrenia.

The relationship between hypothalamic-pituitary-adrenal (HPA) axis function and platelet monoamine oxidase (MAO) activity was examined in drug-free depressed (n = 32) and schizophrenic (n = 36) inpatients. HPA function was measured by determining plasma cortisol levels at 8:30 a.m. and 11 p.m. before, and 8:30 a.m., 4 p.m., and 11 p.m. after administration of 1 mg of dexamethasone (DEX). There was a significant correlation between platelet MAO activity and all post-DEX cortisol levels (8:30 a.m., 4 a.m., and 11 p.m.) in depressed patients, and MAO activity and pre-DEX cortisol levels (11 p.m.) in schizophrenic patients. MAO activity was significantly higher in depressed DST nonsuppressors than in suppressors, and there were more DST nonsuppressors in high-MAO groups as compared with low-MAO groups. Our results thus suggest a strong relationship between platelet MAO activity and HPA function in depressed patients. These biochemical markers are potentially useful in the identification of biochemically and clinically homogeneous subgroups of depressed patients.


Auditory sensory gating and catecholamine metabolism in schizophrenic and normal subjects.

Diminished neuronal response to repeated sensory input is a sensory-gating phenomenon that has been found to be deficient in schizophrenic patients. For example, schizophrenic patients fail to decrease the amplitude of the P50 wave of the auditory evoked potential to the second of paired click stimuli. In some studies, however, normal subjects have also failed to decrease their P50 responses. The aim of this study was to determine if accommodation to the recording situation over time would affect the gating of the P50 response. The gating of the P50 wave is measured as the ratio of the amplitude of the second response to the amplitude of the first. Three successive auditory evoked potentials were compiled, each from trains of 32 pairs of stimuli. Twelve normal subjects and 12 schizophrenic patients were studied. Unconjugated catecholamine metabolites were measured from venous samples drawn before and after the electrophysiological recording. Between the first and third trials, the normal subjects significantly increased their gating of P50. This increase in gating of P50 was related to decreased levels of the noradrenergic metabolite 3-methoxy-4-hydroxyphenylglycol. No similar phenomenon was observed in the schizophrenic patients, a number of whom had a further decrease in P50 gating over the three trials. Transient failure to observe gating of P50 in normal subjects may be related to increased state-dependent noradrenergic activity, which is known to disrupt sensory gating. This mechanism does not seem to account for the more persistent failure of sensory gating in schizophrenia.


Secondary social phobia in patients with major depression.

Nineteen of 42 (45.2%) patients were socially phobic when and only when depressed. Each of these patients met diagnostic criteria for primary depression (Research Diagnostic Criteria) and major depression (DSM-III-R). Every subject had three or more distinct episodes of depression. Eight of the 9 men (88.9%) and 11 of the 33 women (33.3%) were socially phobic when depressed (p = 0.004). Patients with recurrent wintertime episodes of major depression (p = 0.036) and a past history of alcohol or drug abuse were more likely to be socially phobic (p = 0.0001). The authors suggest the 19 socially phobic patients with primary depression should be regarded as having secondary social phobia. Secondary social phobia may be an important source of comorbidity in patients with primary depression.


Panic disorder and major depression: a comparative electroencephalographic sleep study.

Family studies suggest some common etiological factors in panic disorder and depression. The observation of characteristic depression-like polysomnographic alterations in panic disorder patients would further underline the assumed biological interface between the two psychiatric disorders. In a polysomnographic study of 22 inpatients with panic disorder, 12 inpatients with major depression, and 12 control subjects, we found that both groups of patients had one major feature of depression-like sleep: a shortened rapid eye movement (REM) latency. However, the patterns of the first hours of polysomnography showed more differences than similarities between these psychiatric disorders, indicating that the shortened REM latency apparently is merely a common final pathway of different alterations in sleep regulation. Our findings, therefore, provide more evidence against than for a significant biological interface between panic disorder and depression.


Relationship between symptoms rated with the Positive and Negative Syndrome Scale and brain measures in schizophrenia.

The Positive and Negative Syndrome Scale (PANSS) was used to rate clinical symptoms in 42 inpatients with schizophrenia before they were examined by computed tomography. Significantly higher mean size of lateral and third ventricles, and higher mean cortical atrophy were found in schizophrenic patients compared with healthy control subjects. Ventricular enlargement and cortical atrophy were significantly related to low scores on the Composite subscale of the PANSS. Positive correlations were observed mainly with negative items such as blunted affect, emotional withdrawal, difficulties in abstract thinking, passive-apathetic social withdrawal, and lack of spontaneity of conversation. Additional positive correlations were observed with two items from the General Psychopathology subscale (mannerisms and disorientation). Inverse correlations were found with most positive items. These results suggest a relationship between brain structural abnormalities and the symptomatology of schizophrenia recorded with PANSS.


In vivo assessment of pituitary volume with magnetic resonance imaging and systematic stereology: relationship to dexamethasone suppression test results in patients.

The relationship between dexamethasone suppression test (DST) results and in vivo pituitary volume was studied in 24 psychiatric inpatients. The principles of systematic stereology were used to measure pituitary volume from 3-mm contiguous sagittal spin-echo magnetic resonance (MR) images of the brain. There was no correlation between pituitary volume and 3 p.m. or 10 p.m. postdexamethasone (post-DEX) plasma cortisol concentrations. However, when multiple regression analysis was performed to relate pituitary volume to gender, age, and post-DEX plasma cortisol concentrations, there was a significant relationship between pituitary volume and age, gender, and 10 p.m. post-DEX cortisol plasma concentration. This is the first study to demonstrate a method that directly measures, rather than estimates, in vivo pituitary volume. Furthermore, it suggests that activation of the hypothalamic-pituitary-adrenal axis in psychiatric patients, as manifested by elevated post-DEX cortisol concentrations, may influence pituitary volume.


Lithium determination in outpatient clinics by an ion-selective electrode in venous and capillary whole blood.

The use of an ion-selective electrode (ISE) to determine lithium (Li) in routine clinical application was evaluated by repeatedly analyzing reference specimens (precision evaluation) and by comparing blood concentrations in Li-treated patients assessed by ISE and flame emission spectrometry (FES) (correlation and agreement). Precision evaluation was sufficiently high. Li values determined by ISE in venous and capillary whole blood showed high correlations with FES plasma values (correlation coefficients between 0.86 and 0.99). Within the therapeutic range (0.3-1.0 mmole/l Li), agreement was sufficient for venous and less satisfactory for capillary blood (mean differences, FES minus ISE: -0.03 and -0.11 mmole/l Li). Above the therapeutic range, ISE values markedly exceeded FES results.


Age and the dexamethasone suppression test: results from a broad unselected patient population.

We examined the relationship between age and postdexamethasone serum cortisol concentration in 676 psychiatric inpatients with a variety of DSM-III diagnoses. Regardless of diagnosis, patients 65 years and older had significantly higher nonsuppression rates than those below age 65 (64% vs. 34%). The correlation between age and cortisol level was moderate, but significant. Aging is associated with increasing nonsuppression rates to dexamethasone, and this change is augmented by an affective disorder diagnosis. Levels of nonsuppression and age-cortisol correlations vary depending on dose of dexamethasone, diagnosis, and gender.


Affective response to color-slide stimuli in subjects with physical anhedonia: a three-systems analysis.

Emotion-provoking visual stimuli were presented to college undergraduates identified as anhedonic or normal, based on their scores on the Physical Anhedonia Scale (Chapman, Chapman, & Raulin, 1976). The affective stimuli (35 mm color slides) were chosen to elicit a wide range of both positive and negative emotion, with emotional response assessed through affective judgments, viewing time, and monitoring of a variety of physiological systems (heart rate, skin conductance, and facial musculature). The experiment was successful in demonstrating differential emotional response in the two subject groups; anhedonic subjects reported a less positive response than control subjects to positive and neutral stimuli and showed no association between heart rate and the emotion content of the slides. Paradoxically, activity in the muscles of facial expression was greater in anhedonic than control subjects during the presentation of both positive and negative slides. No between-group differences were noted in the viewing-time measure. The results are discussed in the context of Lang's bioinformational theory of human emotion (Lang, 1984, 1985).


Tonic and phasic electrodermal measures of human aversive conditioning with long duration stimuli.

Two experiments investigated phasic and tonic electrodermal responding to long, variable-duration stimuli in aversive conditioning procedures. Experiment I demonstrated reliable differential conditioning on both phasic (first interval response, FIR) and tonic (change in skin conductance level, delta SCL; spontaneous fluctuations) measures, using 10-40-s slides as conditioned stimuli (CSs) and electric shock as the unconditioned stimulus (UCS). Experiment 2 examined the sensitivity of phasic and tonic measures to UCS aversiveness. Both FIR and delta SCL were greater to a conditioned stimulus paired with shock than one paired with an innocuous reaction-time warning tone. Responding was reversed when the reinforcement contingencies were reversed. It was suggested that, with long duration CSs and an aversive UCS, phasic measures to stimulus onset, such as FIR, may reflect both stimulus significance and threat appraisal, whereas tonic measures reflect primarily arousal or anxiety arising from anticipation of the aversive unconditioned stimulus.


Fearfulness and startle potentiation during aversive visual stimuli.

Recent experimental research suggests an association between negative affect and potentiation of the human startle reflex, as well as enhancement of this effect among fearful compared to low fear subjects. In the present study, 32 undergraduates were selected for high or low total Fear Survey Schedule scores. Acoustic startle probes were presented while subjects received warned presentations of aversive and neutral photographic slides. High fear but not low fear subjects showed potentiated short-latency cardiac acceleration and blink magnitude, and reduced blink latency, during aversive compared to neutral slides. These results support the hypothesis that affective modulation of startle is enhanced among high fear compared to low fear subjects. Considered in the context of prior findings, the results suggest that this individual difference effect generalizes across psychophysiological components of the startle reflex and diverse procedures for manipulating affect.


Concomitant heart rate and eyeblink Pavlovian conditioning in human subjects as a function of interstimulus interval.

Pavlovian heart rate and eyeblink conditioning were simultaneously assessed in human subjects. Tone durations of 0.6, 1.1, and 2.1 s were employed in separate groups of subjects as the conditioned stimulus. A 100-ms corneal airpuff, which served as the unconditioned stimulus, overlapped the last 100 ms of the tone in each group, thus producing interstimulus intervals of 0.5, 1.0, and 2.0 s. Other groups of pseudoconditioning subjects received explicitly unpaired tone and airpuff presentations of identical durations but in a pseudorandom sequence so that they never occurred together. The best eyeblink conditioning was observed in the group with the .5-s interstimulus interval, although the 1.0-s group also demonstrated some evidence of eyeblink conditioning. The group with the 2.0-s interstimulus interval showed a lower overall rate of conditioned response occurrence and the highest rate of pseudoconditioned responding. The conditioned heart rate response in all three conditioning groups consisted of cardiac decelerations, but tone-evoked cardiac accelerations were observed in the pseudoconditioning groups. The magnitude of the cardiac deceleration was comparable in all three conditioning groups.


Taking attention to task: P300, task response probability, and within-category deviation detection.

Previously, we reported enhanced P3 amplitudes to between-category deviations among high and low probability events. Here, we tested the effects of a within-category difference. Subjects performed a go/no-go button press task as they viewed repeated, randomly-ordered presentations of nine double-digit numbers. Eight numbers fell within a prescribed range (42-49, standards); prior to testing, subjects selected one standard number for later recall. A ninth, out-of-range (91, deviant) number was also included. Subjects were tested under two conditions, in which they responded either to one (low response probability) or to seven (high response probability) standard nonselected numbers, designated as targets. Relatively larger P3s were consistently apparent only when the deviant nontarget was associated with a low probability response to a nontarget. There was a selective effect of nontarget response probability on P3 amplitude to the deviant nontarget. Our results indicate that within-category deviation detection is facilitated by "controlled" attention to the structure of the stimulus field.


Word frequency and multiple repetition as determinants of the modulation of event-related potentials in a semantic classification task.

We recorded event-related potentials while subjects performed a category membership decision task. The stimuli were words of high and low frequency of occurrence in written English, and each was presented four times. The experiment was intended to explore the interaction of word frequency and multiple repetition on the event-related potential, and thence to investigate the possible loci in time of the effects of these variables. First presentations of low and high frequency words evoked event-related potentials which differed in the presence, in the low word frequency waveforms, of a right-hemisphere dominant negativity peaking at 400 ms. This negativity was very similar to the N400 which may be sensitive to the semantic relations among words in a sequence. Initial repetition diminished this midlatency difference, but gave rise to both earlier and later frequency-related differences. Subsequent multiple repetition abolished the early frequency-related repetition effect, but did not affect amplitudes in the region of N400, nor did it abolish a late positivity, present only for repeated low frequency words.


Interactive effects of difficulty and instrumentality of avoidant behavior on cardiovascular reactivity.

College-aged subjects performed 35 trials of an easy or difficult digit-recognition task. Half were told that a good performance would ensure a high chance of avoiding a blast of noise, and half were told that a good performance would ensure a low chance of avoiding the noise. Results indicated that heart rate and systolic blood pressure reactivity were higher in the difficult condition than in the easy condition only when the probability of avoiding the noise (given success) was high. When the probability of avoiding the noise (given success) was low, heart rate and systolic responsivity were low regardless of task difficulty. It also was found that (1) performance quality was poorer overall among difficult subjects than among easy subjects, and (2) that the difference in performance quality between the easy and difficult groups was somewhat (not significantly) greater in the low-probability conditions than in the high-probability conditions. Major findings are considered in terms of Obrist's reasoning regarding the psychophysiological consequences of active coping and a motivational model by Brehm, which specifies conditions under which individuals will be more and less task engaged.


Analysis of pattern-reversal visual evoked-potential topography: replicability in normal subjects and comparisons with Alzheimer's disease.

This paper reports two studies using multivariate analysis to aid the interpretation of cross-coherence of multiple electrode sites in evoked potential responses. In the first study, the replicability of principal components and multidimensional scaling was evaluated by applying both methods to pattern-reversal visual evoked potentials recorded from 28 scalp sites in two subgroups of sex- and age-matched healthy subjects, and then comparing the results. Four dimensions replicated in the two initial multidimensional scaling solutions and appeared to reflect differences in: 1) anterior versus posterior scalp areas, 2) laterality, 3) separation of frontal and occipital sites from other scalp regions, and 4) proximal versus distal placements. The initial principal components did not match well in the two groups, but rotation to congruence improved their replicability and ultimately yielded axes similar to those of the multidimensional scaling dimensions. In the second study, Alzheimer's disease and sex- and age-matched control subjects were evaluated. The four axes identified were the same as those described above, but after the solutions were rotated to align them, the group differences appeared negligible. Examination of the components and dimensions from both studies showed some consistent departures from being merely reflectors of site location, and the apparently visual dimension appeared clearly in all four groups. Judged on the basis of initial interpretability and replicability of the solutions, the results suggest that multidimensional scaling, with appropriate transformation, may provide an effective tool for analyzing pattern-reversal visual evoked-potential topography.


Comparison of impedance cardiographic measurements using band and spot electrodes.

The comprehensive assessment of cardiac function using impedance cardiography has led to increasingly widespread use of the technique in psychophysiology. Disposable adhesive band electrodes have been the most widely used electrode type, but spot electrode configurations present attractive alternatives in terms of convenience and subject comfort. The present study was designed to evaluate whether one such spot electrode configuration yielded the same information as the more standard band electrodes for cardiac output and systolic time interval measurement. Male and female healthy adult subjects (N = 20) were tested. Comparisons between spot and band electrodes were made for the absolute magnitude of cardiac output and systolic time intervals, as well as for responses to the highly reproducible effects of bicycle exercise. Consistent with previous findings, systolic time interval measurements were unaffected by electrode type. However, for cardiac output measurements, differences between spot and band electrode measurements were found. Under resting conditions, the absolute magnitudes of cardiac output values measured using spot electrodes were smaller than for band electrodes. Subtle, yet significant differences were also found for cardiac output responses to exercise, with spot electrodes indicating greater increases in cardiac output than band electrodes. At the same time, anticipated gender differences found for cardiac output at rest and in response to exercise were unaffected by electrode type. Overall, these findings suggest that when comparing the results of studies that have utilized different impedance electrode types, it would be prudent to remain alert to the possibility of confounding influences.


Alternate cardiovascular baseline assessment techniques: vanilla or resting baseline.

The accurate evaluation of cardiovascular reactions to psychological challenge requires stable baselines against which change can be evaluated. When more than one challenge is employed, the recovery of this baseline becomes important in order to avoid carryover effects. Resting periods, even those of 20 min or more, do not guarantee baseline stability. We compared a 20-min resting condition and a new form of baseline condition in 48 college men using video tasks as the psychological challenges. The new form was a minimally demanding color detection task, termed the "vanilla" baseline condition. A 10-min version and a 20-min version of this condition were tested. Comparisons to 10-min resting baselines were made using our prior work and values from the literature. Vanilla baseline conditions were shown to be equal to or better than resting baseline conditions using criteria of between- and within-baseline stability, amplitude and significance of responsivity, and generalizability between sessions on separate days. Ten-minute resting baselines also showed acceptable stability, questioning the value of lengthy baselines. The good performance of the 10-min vanilla baseline in initial and replication samples supported its utility for estimating baselines for many purposes.


Developing a level III/IV medical/psychiatry unit. Establishing a basis, design of the unit, and physician responsibility.

This article is part of a series defining the administrative, logistical, and funding issues necessary for the establishment of a medical/psychiatry unit. It emphasizes the experience of individuals who have developed such units and is offered in an attempt to prevent duplication of costly mistakes. Administrative issues, factors affecting the physical design of the unit, requirements for medical coverage and medical and psychiatric programmatic support, and the ethical issues encountered in managing such a unit are discussed.


Categorization of types of medical/psychiatry units based on level of acuity.

Medical/psychiatry units can be categorized by the level of acuity of medical and psychiatric illness. Type I units are categorized as those that primarily provide psychiatric care with a low level of medical acuity. Type II units include general medicine or medical subspecialty units that are associated with a psychiatric liaison service and provide low levels of psychiatric care to those admitted to the general medical setting. Type III and Type IV units are characterized by a true departure from the current ward settings and care for patients who have concurrent and more severe medical and psychiatric problems in a unified setting. Both of these units require special physical changes in the ward structure, additional nurse training, and coordinated physician coverage to function effectively.


Quality assurance in a setting designed to care for patients with combined medical and psychiatric disease.

In an attempt to address the needs of patients with combined medical and psychiatric illness, a variety of clinical centers are now creating medical/psychiatry units. These units differ widely in their clinical capabilities, yet no adequate delineation of safeguards regarding quality of care currently exists. This article discusses minimum quality guidelines for four types of medical/psychiatry units that are based on the level of acuity of patients' medical and psychiatric disease.


The chronically ill child and family stress. Family developmental perspectives on cystic fibrosis.

The authors take a developmental and family systems perspective in reviewing research on the family stressors inherent in caring for a child with a chronic disease. Cystic fibrosis, a genetically transmitted and life-shortening disorder, exemplifies a chronic disease that places demands on the family that are both unique and shared with other prolonged illnesses. The authors chronicle the interaction of the debilitating features of this disease and its demanding treatment regimen with family dynamics from the point of initial diagnosis to the terminal stages.


An animal model for delirium.

This study describes an animal model for delirium comparing rats treated with either saline or atropine. The model was defined by recordings of cortical EEGs, maze performance, and behavioral observations. EEG slowing and increased amplitude, difficulty with attention and memory, sleep-wake cycle reversal, and changes in behavior (lack of focused direction, irritability, fluctuating levels of activity, excessive random sniffing) appeared consistent with signs and symptoms seen in human delirium. EEG abnormalities in atropine-treated rats returned to normal before cognitive deficits did. Motor activity monitoring did not reveal diminished motor activity as a confounding variable in maze performance.


Physical symptoms and depressive symptoms among individuals with HIV infection.

The authors investigate the importance of physical symptoms as a correlate of depressive symptoms and suicidal thoughts in a large (N = 881) community-based sample of persons infected with human immunodeficiency virus. The study overcomes limitations of prior research by minimizing overlap in measures of affective and physical symptoms, studying a more diverse population, and including correlates such as measures of social support, function, employment, insurance coverage, and cognitive impairment in the analysis. The authors' data support the notion that in diagnosing depression in the medically ill, concern over isolating physical symptoms as either "affective" or "physical" may be exaggerated.


Bulimia nervosa. Four uncommon subtypes.

The histories and psychological profiles of more than 500 patients meeting DSM-III-R criteria for bulimia nervosa were reviewed. A total of 310 patients demonstrated the most characteristic pattern of bulimia, with finger-induced purging and occasional diet pill, diuretic, or laxative abuse. Seventeen patients reported binge eating with no self-induced vomiting but with severe laxative abuse (i.e., greater than or equal to 50 laxatives daily). A total of 126 patients reported bulimia with finger-induced purging and regular mild (i.e., 2-3 daily) laxative abuse. Eight patients reported bulimia without finger-induced purging, diuretic, or laxative abuse but with the regular abuse of ipecac as a means of inducing vomiting. Four clinical subtypes of bulimia were seen. These were overt bulimia, which occurred in 8.9% of the sample; obsessive-ritualistic bulimia, which occurred in 2% of the sample; sexually evocative bulimia (Fatal Attraction Syndrome), which occurred in 2.9% of the sample; and masochistic bulimia, which occurred in 4.9% of the sample. Each of these subtypes of bulimia are described and defined. The characteristic psychologic profile, clinical features, and implications for treatment and research are discussed.


The power of statistical studies in consultation-liaison psychiatry.

Several authors recently have proclaimed the need for empirically based research articles in consultation-liaison psychiatry. The authors report that although the proportion of empirically based studies published in Psychosomatics increased 148% from 1979 to 1989, the power of statistical analyses and the deleterious effect of multiple tests were often neglected. A power analysis of empirical studies published in the 1989 volume year of Psychosomatics is reported, showing statistical power to be low for all but the most robust of effect sizes.


Psychological modulation of the delayed type hypersensitivity skin test.

Considerable data have demonstrated that psychological states can influence the immune system in animals. Whether human immune function can be intentionally modulated by the central nervous system is unknown. This article presents data from two studies that sought to demonstrate intentional modulation of the immune system by psychological interventions. It also discusses the methodological complexities involved with this type of research in humans.


[Legionnaires' disease in intensive care patients. Results of plain film thoracic radiography].

We reviewed the chest radiographs and clinical data of 30 patients in an intensive care unit with legionellosis diagnosed by significant serological findings (n = 18), microscopic demonstration of the organism in the transtracheal aspirate (n = 5) or both (n = 7) and investigated the correlation between the identification of Legionella and signs of pulmonary infection. In 13 patients legionnaires' disease was diagnosed with a high degree of confidence. Typical radiographic findings included distal air space disease, which initially appeared to be unilateral, progressing towards bilateral infiltrates. Patchy infiltration at the onset of disease was followed by consolidation. Small pleural effusions were common, while no abscess formation was observed. Characteristically, infiltration persisted for weeks even with clinical convalescence. These radiological findings correspond well with observations in otherwise healthy patients with legionnaire's disease. In 10 patients the etiology of pulmonary infiltrates could not be identified. Seven patients did not develop radiological or clinical signs of pneumonia; therefore, the serological/microscopic detection of Legionella was not interpreted as legionnaires' disease. According to the results of our investigation the diagnosis of legionnaires' disease requires radiological findings in addition to laboratory data.


[An economic comparison between digital luminescence radiography and conventional film processing in intensive care medicine].

The costs of a conventional film-screen radiography daylight-system and storage-phosphor computed radiography (Fuji AC-1) are compared. In 1990, 3841 radiologic procedures (mostly portable chest X-rays) were performed in 3474 patients of a surgical intensive care unit. With conventional film-screen radiography 6.8% retakes were necessary for diagnostic or technical reasons. Comparing the fixed and variable costs of both systems conventional film-screen radiography was more economic under the given conditions of the test. It is concluded that computed radiography in intensive care patients has definite advantages in terms of image quality and reproducibility, however, in order to compete successfully in the economic turf CR has to be implemented in a picture archiving and communication system (PACS).


[The x-ray clinical picture and evaluation criteria of implantable cardioverter-defibrillator systems].

Since the first implantation of an automatic cardioverter defibrillator (ICD) in February 1980, the therapy of ventricular tachyarrhythmia has been changed drastically. The original therapy with antiarrhythmic agents has been increasingly replaced by the implantation of the ICD. The radiologist should be aware of the different types of ICDs and their normal appearance, because thorax radiography is often used during regular routine follow-up of the ICD system. The different types of ICDs, their normal radiological appearances, the indications and the implantation technique are discussed in the present study. The radiologist has to interpret the radiographs with respect to the electrodes, the device and changes in heart configuration. Major migration of electrodes is visible, but the detection of little changes in configuration is only possible with the help of serial radiographs. If extraperitoneal placement of the device is suspected, an ultrasound examination should be obtained. An important complication for the radiologist is a possible deactivation of some devices by electromagnetic interference.


[Splenic complications in inflammatory pancreatic diseases].

Pancreatitis in combination with splenic and vascular complications is dangerous and potentially lethal. The most common complications are intestinal or intraperitoneal hemorrhage resulting directly from either vascular changes, such as erosion of the splenic artery, formation of a pseudoaneurysm, hemorrhage into a pseudocyst, or rupture of a pseudocyst with perforation into the colon, or complications in the spleen, such as anemic or hemorrhagic infarction, abscess or rupture. CT is the method of choice for the diagnosis of splenic complications of pancreatitis. Angiography is indicated in every severe hemorrhage in the presence of pancreatitis, to demonstrate vascular changes and to localize the source of hemorrhage. In addition, acute arterial bleeding can be successfully treated with catheter embolization.


[Radiologic diagnosis of maxillary sinus aspergillosis].

Aspergillosis of the maxillary sinuses shows an increasing incidence in even otherwise healthy patients. Next to inhalation as the mode of infection, a dental root canal filling with an orosinusal fistula can be the cause. As most infections remain initially undetected or underestimated as common sinusitis, early diagnosis must be achieved. Standard X-ray of the paranasal sinuses, conventional tomography as well as CT scans are of major importance. Centrally located hyperdense opacifications are a good criterion and can be best seen in CT. Even when the case has not progressed too much, radical surgery combined with Amphotericin B therapy is still the treatment of choice since the infection may progress rapidly.


[Diagnosis of pulmonary sarcoidosis using high-resolution computed tomography].

This report deals with 24 patients with pulmonary manifestations of sarcoidosis who were examined by means of high-resolution computed tomography. The characteristic findings were rounded masses of all sizes and shapes. Other findings were ground glass opacities and thickened septal walls. In the advanced stage fibrous strands and intrapulmonary cavities could be seen. High-resolution tomography allows better detection of fine granulomas and better recognition of their anatomic relationship to the pulmonary substructures, facilitating differential diagnosis against other interstitial lung diseases.


[Pulmonary arteriovenous fistulas in Osler's disease].

In a retrospective study over a period of 10 years we found 16 patients with Osler's disease and associated pulmonary arteriovenous fistulas in the hospital of the University of Heidelberg and the Thoraxklinik Heidelberg-Rohrbach. We report about the radiologic diagnostic findings and the clinical manifestations of this defined pulmonary malformation. Radiologic findings are round or oval lobulated homogeneous masses. The size ranges from < 1 to several centimeters in diameter, most fistulas were located in the lower lobes. Feeding and draining vessels can be identified frequently on plain radiographs or tomograms/CT. Best procedure to recognize these malformations is the selective pulmonary arterial angiography.


Insulin, insulin-like growth factors and glucose transporters: temporal patterns of gene expression in early murine and bovine embryos.

mRNA phenotyping by the reverse transcription-polymerase chain reaction (RT-PCR) method was used to compare the patterns of expression of insulin and insulin-like growth factor (IGF) ligand and receptor genes in preimplantation bovine embryos with those established previously for preimplantation murine embryos. In the early bovine embryo, transcripts for IGF-I, IGF-II and mRNAs encoding receptors for insulin, IGF-I and IGF-II were all detectable at all embryo stages from the 1-cell zygote to the blastocyst. In the mouse, IGF-II ligand and receptor mRNAs were not expressed until the 2-cell stage, and the insulin and IGF-I receptor mRNAs were not detectable until the 8-cell stage. Since transcriptional activation of the embryonic genome occurs at the 8- to 16-cell stage in the bovine embryo and at the 2-cell stage in the murine embryo, it is suggested that these transcripts are products of both the maternal and embryonic genomes in the bovine embryo whereas in the mouse they are present only after activation of the embryonic genome. Transcripts for insulin were not detected in preimplantation embryos of either species. Colloidal-gold immunocytochemistry with antibodies directed against the insulin receptor, IGF-I receptor and IGF-I ligand has confirmed the presence of these molecules in bovine blastocysts. RT-PCR and indirect immunofluorescence procedures demonstrated that the glucose transporter (GLUT) isoform 1 is present in murine embryos from the oocyte to blastocyst stage whereas GLUT 2 expression begins at the 8-cell stage.


Metabolic and developmental responses of preimplantation embryos to platelet activating factor (PAF).

Platelet activating factor (PAF) is an ether phospholipid produced by preimplantation embryos of a number of species. Production of PAF by embryos has been measured by detecting thrombocytopenia in a splenectomized mouse bioassay, platelet aggregation bioassays in vitro and a specific radioimmunoassay. Production is highly variable and is adversely affected by culture in vitro. It has, however, been correlated with morphology, development rates in vitro and the pregnancy potential of embryos following transfer. Investigations using PAF-antagonists have established an essential role for PAF in early pregnancy. Together with studies that have shown PAF to have direct effects on embryonic metabolism during culture in vitro, these observations suggest that PAF acts as an embryonic autocoid. Hence, a major site of action for embryo-derived PAF in vivo is the embryo itself. Supplementation of embryo culture media with PAF had no effect on the rate of development in vitro of 2-cell mouse embryos through to the blastocyst stage. However, PAF increased cell numbers of blastocysts cultured from the 2-cell stage and the mitotic index of embryos at both the 8-cell and blastocyst stages. Supplementation of culture media with PAF has also been shown to increase the implantation potential of both mouse and human embryos cultured in vitro. In the mouse, the effect of PAF in enhancing implantation rates was most evident when the developmental potential of untreated embryos was suboptimal. These observations suggest that the production of embryo-derived PAF is one limiting factor in maintaining the viability of embryos cultured in vitro.


Actions of platelet activating factor (PAF) on gametes and embryos: clinical aspects.

Platelet activating factor (PAF) is a phospholipid widespread in body tissues. Previous reviews have discussed its production by preimplantation embryos and the evidence implicating it as an autocrine mediator in aspects of gamete and embryo physiology. Human spermatozoa contain variable amounts of PAF, the amount contained depending on the source and method of preparation of the sperm. Incubation of human sperm with PAF tends to increase their forward velocity, especially in samples with slow motility. PAF treatment causes an increase in the proportion of acrosome-reacted sperm and in their ability to penetrate both zona-free hamster ova and cervical mucus. PAF has been found in human follicular fluid at ovulation. A role for PAF in ovulation has been suggested, because PAF antagonists reduce the rate of ovulation in rats. In some studies, modest improvements to mouse in vitro fertilization (IVF) rates have been achieved with PAF supplementation of media under specific conditions. Furthermore, in the rabbit and mouse, PAF antagonists have been reported to inhibit fertilization in vivo and in vitro respectively. However, addition of PAF to human IVF medium, but only at the time of insemination and fertilization, had no effect on either fertilization or pregnancy rates. Sensitive bio- and immuno-assays have shown that PAF is secreted by human embryos into their fluid milieu. PAF secretion by these zygotes during culture, although markedly variable, has been correlated with the achievement of pregnancy and pregnancy outcome. Although the secretion of PAF by the mouse embryo decreases during culture in vitro, exogenous PAF enhances embryo viability during culture. Similarly, culture of human zygotes in PAF-supplemented medium prior to embryo transfer significantly increases the chance of achieving pregnancy. Both the implantation and live-birth rates are increased in human IVF by addition of PAF to the medium.


Early pregnancy factor has immunosuppressive and growth factor properties.

Early pregnancy factor (EPF) was first described as a pregnancy-associated substance, although recent studies suggest a more general link with cell development. It is a product of actively dividing cells and its apparent functional importance to them suggests its potential as a regulator of cell proliferation. The recent discovery of EPF in platelets has provided a comparatively rich and readily available source of EPF. The purification procedures employed to isolate EPF from this source have also been applied to pregnancy serum and urine, medium conditioned by oestrous mouse ovaries (stimulated with prolactin and embryo-conditioned medium), medium conditioned by tumour cells, and serum from rats 24 h after partial hepatectomy (PH). In all instances, biological activity followed the same pattern throughout. Furthermore, the final active reversed-phase high-performance liquid chromatography fraction from all sources was bound specifically by immobilized anti-EPF monoclonal antibodies (MAbs), indicating that the active fractions produced from these diverse sources are very closely related, if not identical. Some differences have been observed in the behaviour of EPF in various conditions. EPF is produced by proliferating tumour cells and by liver cells post-PH, and passive immunization studies with anti-EPF MAbs have shown that these cells need EPF for survival. In contrast, EPF has not been detected as a product of the pre-embryo, and addition of anti-EPF MAbs to embryo cultures does not adversely affect development from the 2-cell to the blastocyst stage. Although the pre-embryo is not dependent on EPF for its development in vitro, neutralization of EPF in vivo by anti-EPF MAbs retards its development. Thus, EPF appears to play an indirect role in maintaining the pre-embryo. By virtue of its ability to suppress the delayed-type hypersensitivity reaction, it has been suggested that EPF might act as an immunological response modifier of the maternal immune system. Alternatively, the effect of EPF on lymphocytes may be to reduce the expression of all or some cytokines and this could inhibit development. Whether or not EPF acts more directly as an autocrine growth factor from around the time of implantation, when the embryo first begins synthesis of EPF, is not known and remains to be investigated.


Identification of molecules and mechanisms involved in the 'early pregnancy factor' system.

For a long time the 'early pregnancy factor' has defied molecular definition. First described in 1976, this phenomenon is revealed in vitro by the rosette inhibition assay, in which a lymphocyte-modifying activity in maternal serum is detected within hours of fertilization; it is present for at least the first two-thirds of pregnancy, with continued detection dependent upon the presence of a viable embryo or fetus. It has potential applications in early pregnancy testing, for monitoring fetal well-being and in the study of fertility control. Although the activity detected is one of a complex biological fluid (pregnancy serum) in a complex biological assay, this ability of pregnancy sera to cause increased rosette inhibition titres (RIT) has generally been ascribed to the presence of an 'early pregnancy factor' (EPF). The common usage of the term EPF has implied the existence in pregnancy sera of a unique factor, which has often been assumed to be a novel, pregnancy-specific protein with the unique capacity to induce increased RITs. Recent results render this concept untenable. These studies have begun to identify the molecules and mechanisms which cause the expression of increased RITs. In particular, thioredoxin or thioredoxin-like molecules have been identified as involved in the mechanisms by which pregnancy sera induced increased RITs. As a result, a new paradigm for the EPF phenomenon is presented which helps to resolve many of the enigmatic properties previously ascribed to the so-called 'early pregnancy factor' and which may assist in the further understanding of the molecular mechanisms of communication between embryo and mother prior to implantation.


Granulocyte-macrophage colony stimulating factor (GM-CSF): one of a family of epithelial cell-derived cytokines in the preimplantation uterus.

Granulocyte-macrophage colony stimulating factor (GM-CSF) is one of a number of lympho-haemapoietic cytokines, including CSF-1, interleukin-6 (IL-6) and leukaemia inhibitory factor (LIF) now known to be synthesized by epithelial cells in the murine uterus. GM-CSF synthesis is regulated primarily by the ovarian steroid hormone oestrogen, but is also subject to modulation by factors including a seminal component of seminal vesicle origin which stimulates a 20-fold increase in luminal fluid content at mating, and bacterial lipopolysaccharide (LPS) and the T-lymphocyte and natural killer (NK) cell product interferon-gamma (IFN gamma). In the non-pregnant mouse GM-CSF synthesis peaks at oestrus. Synthesis is maintained at comparable or moderately higher levels during the preimplantation period of pregnancy and in the non-decidualized endometrium during mid gestation. An embryotrophic activity is suggested by studies in vitro that indicate that GM-CSF stimulates attachment and outgrowth of blastocysts. It is postulated that GM-CSF is of major importance to the physiology of pregnancy through its role as a component of a local cytokine circuit acting to recruit and regulate function of endometrial leukocytes, and by its action as interlocutor and important effector arm in embryo-maternal interactions during gestation.


The effect of leukaemia inhibitory factor (LIF) on embryogenesis.

Leukaemia inhibitory factor (LIF) was originally identified as a haemopoetic factor that induced the differentiation of certain myeloid leukaemia cell lines. In contrast to this action, LIF was subsequently shown to inhibit the spontaneous differentiation of murine embryonic stem cells in culture, thus maintaining their pluripotency and ability to contribute to the germline of chimaeric mice. In the mouse, mRNA for LIF is expressed by the endometrial glands of the uterus coincident with the time of blastocyst implantation and receptors have been found on the preimplantation blastocyst. The signal for LIF expression appears to be of maternal origin, perhaps regulated by oestradiol. Recombinant LIF improves the development of murine and ovine blastocysts in culture although there is some species specificity with respect to the type of LIF that is bioactive. It is proposed here that LIF acts on the trophectoderm of the rapidly expanding blastocyst and improves the implantation rate of otherwise compromised embryos. Further studies in livestock should elicit therapeutic uses for LIF in embryo culture, embryo transfer and embryo survival in vivo.


Effects of hypoxia on morphological and biochemical characteristics of renal epithelial cell and tubule cultures.

Apoptotic cell death plays an important role in the pathogenesis of renal atrophy in diseases of the kidney involving chronic mild ischemia. The present study constitutes an in vitro model of these diseases and assesses the modes of cell death involved after hypoxic treatment of renal epithelium. Cultures of MDCK cells or primary cultures of rat renal parenchymal tubules were treated in either a physiological or a hypoxic atmosphere. Cultures were collected before treatment and at 24 h and 48 h, for morphological and biochemical studies. Both apoptosis and necrosis were observed at significantly increased levels by 48 h of hypoxia in the MDCK cell cultures. DNA gel electrophoresis patterns supported these findings. Experiments using tubule cultures demonstrated that, during the 48 h of study, tubular epithelial cells in the center of the control tubule structures died by apoptosis, possibly as a result of mild oxygen and/or nutrient depletion. With added hypoxic treatment, however, the entire tubule structure became necrotic. Results are similar to those found during in vivo studies, thus providing in vitro models that may be developed further to define factors in the pathogenesis of some renal diseases.


Ischemia-reperfusion induced acute renal failure in the rat is ameliorated by the spin-trapping agent alpha-phenyl-N-tert-butyl nitrone (PBN).

The spin-trapping agent alpha-phenyl-N-tert-butyl nitrone (PBN) reduced the ischemia-reperfusion induced acute renal failure in the rat. Renal ischemia was produced in unilateral nephrectomized rats by complete occlusion of the left renal artery for 60 min. Perfusion of the kidney was then reestablished, and the rats were sacrificed 48 h later. PBN (100 mg/kg i.p.) administered 30 min prior to renal artery occlusion significantly reduced the increase in serum creatinine and urea and renal failure index, as well as the decrease in urine/plasma creatinine ratio and creatinine clearance compared to saline-injected ischemic rats. PBN injected to control rats had no effect on these parameters. These data support the hypothesis of an involvement of reactive free radicals in the pathogenesis of ischemia-reperfusion induced acute renal failure in the rat and suggest that PBN may be a useful agent for the prevention of renal ischemia-reperfusion damage.


Alterations of gluconeogenesis by ischemic renal injury in rats.

This study was designed to determine changes in one metabolic function, gluconeogenesis (GLG), after ischemic renal injury. Tubule suspensions were prepared by collagenase treatment of SD rat kidneys on 1, 3, and 7 days after left renal artery and vein occlusion for 0-90 min and incubated in Krebs-Henseleit buffer with or without 2 mM pyruvate or malate aerobically. Glucose contents were assayed photometrically. On days 1 and 3 after ischemia for longer than 60 min, serum creatinine levels rose significantly. The tendency of increase of GLG was observed on days 1 and 3 after 10-60 min of ischemia. GLG increased significantly on day 1 after 30-min ischemia. On the other hand, GLG decreased significantly on day 1 after 90-min treatment. Morphologic damage was limited to the corticomedullary region on days 1 and 3 after ischemic times of 30 and 60 min. These results suggest that renal GLG is stimulated to supply energy for ATP decrease by ischemia and for further regeneration in extraproximal segments along the nephron.


Reduction of CyA nephrotoxicity by nifedipine during and after experimental in situ renal preservation.

In order to evaluate the role of nifedipine in the nephrotoxic effect induced by both ischemia and CyA, 18 healthy mongrel dogs were used. The kidneys were exposed and subjected to 1 h of ischemia by clamping both renal vessels. To the renal artery of the first group of kidneys (n = 9), 300 mL of cold Euro-Collins solution, in which nifedipine (Bay a 1040-10 mg) was diluted, was infused for 15 min (nifedipine group), while 300 mL of cold Euro-Collins solution plus 10 mg of placebo (Bay a 1040-placebo) was infused to the renal artery of the second group (n = 9) of kidneys (placebo group). Venous drainage was effected through a plastic cannula. All animals received through a nasogastric catheter 20 mg/kg cyclosporine A at the beginning of the ischemia. The 1 h of ischemia was divided in a 15-min period of cold ischemia and 45-min of warm ischemia, at the end of which the clamps were removed. During the 2 h (30 min x 4) after reperfusion, 10 mg of nifedipine and placebo was administered additionally by a peripheral vein to the nifedipine and the placebo group, respectively. Then the kidneys were removed for histological study. Urine volume and creatinine and urea clearances of the nifedipine group were significantly higher than the placebo group (p < 0.001) while TxB2 levels were higher in the placebo group in all studied periods (p < 0.001). Urine sodium, FENa, osmolar clearance, and LDH values were significantly different (p < 0.01), but the urine potassium concentration was not different in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)


Acute cyclosporin A renal dysfunction in dogs reversed by calcium antagonists and antiplatelet agents.

The aim of this study was to assess the effect of nifedipine and piracetam alone or in combination in the protection of renal function and morphology after cyclosporin A (CyA) administration. Thirty healthy mongrel dogs with a mean body weight of 15 kg were sacrificed. Six animals (group C) were given CyA 20 mg/kg body weight per os, while the remaining groups (8 animals each) were given concomitantly 20 mg nifedipine (group CN) or 4 g of piracetam (group CP), or both drugs in combination (group CNP). After 5 days of drug administration the animals were anesthetized, both kidneys were exposed, and functional tests were performed. Then the kidneys were removed for histological study. The mean plasma CyA levels in the four groups were 1765 +/- 685 ng/mL, 1300 +/- 324 ng/mL, 1116 +/- 491 ng/mL and 1600 +/- 290 ng/mL, respectively. Urine volume, creatinine, urea, and osmolar clearances were significantly higher in the groups CN, CP, and CNP compared to the control group C (p < 0.01). Urine sodium concentration was significantly higher (p < 0.05 or p < 0.01) in nifedipine groups than in the other two groups of animals, while the fractional excretion of sodium (FENa%) was significantly higher (p < 0.01) in all treated groups compared to controls. Plasma thromboxane-B2 levels were significantly reduced by each drug alone or in combination (p < 0.01). Morphological lesions, similar in all groups, did not correlate with the functional improvement.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of desoxycorticosterone acetate (DOCA) plus saline drinking on gentamicin-mediated nephropathy in rats.

Studies were performed to examine the effect of desoxycorticosterone acetate (DOCA) treatment plus isotonic saline drinking on gentamicin (GM)-mediated nephropathy in rats. GM, 40 mg/kg/day, was subcutaneously injected for 13 days following a 5-week treatment with water drinking or DOCA (10 mg/kg/week) plus saline drinking. Twenty-four hours after the last injection of GM, renal blood flow (RBF) and Cin decreased to approximately 69% and 52% of the control values in water-drinking GM-treated rats, respectively, but was well maintained in DOCA plus saline-drinking GM-treated animals. There was no significant difference in morphologic tubular injury or the renal cortical GM content between GM-treated groups. Saline drinking alone (1% saline, 5 weeks) lessened neither GM-induced reduction in GFR nor tubular damage. Body weight loss occurred following GM injection in the water-drinking group but not in the DOCA plus saline-drinking and saline-drinking-alone groups. DOCA plus saline drinking significantly suppressed the plasma renin activity (PRA) but saline drinking alone did not. A significant inverse correlation was found between PRA and Cin in water-drinking GM-treated and untreated rats. The data suggest that the beneficial effect of DOCA plus saline drinking is associated with renin-angiotensin suppression rather than with the renal GM content or well-maintained hydration.


Tubular injury and regeneration in the rat kidney following acute exposure to gentamicin: a time-course study.

Aminoglycoside antibiotics act as nephrotoxic drugs, inducing a lysosomal phospholipidosis and necrotic lesions essentially in convoluted proximal tubules. Previous studies have demonstrated that tubular injury caused by these compounds elicits a process of renal tissue repair (tubular regeneration) involving an increase of cell turnover in tubular epithelium. The present study was performed in order to: (i) achieve further insight into the temporal relationship between aminoglycoside-induced phospholipidosis, tubular necrosis, and tubular regeneration; and (ii) approach the control of tubular regeneration after nephrotoxin-induced insult. To investigate the latter point, we examined by immunocytochemistry the intrarenal distribution of epidermal growth factor (EGF) during tubular regeneration. Five groups of female Sprague-Dawley rats (n = 5) were treated for 4 days with gentamicin i.p. at a daily dose of 50 mg/kg delivered in 2 injections per day. Sham-treated animals (n = 5) received an equivalent amount of vehicle (0.9% NaCl) according to the same protocol. Groups of treated rats, and controls, were terminated 16 h (day 1), 4 days, 7 days, 14 days, and 21 days after the end of gentamicin administration. One hour prior to necropsy, each animal was given an i.p. injection of 40 mg 5-bromo-2'-deoxyuridine (BrdU) for the immunocytochemical demonstration of S-phase cells, using an anti-BrdU monoclonal antibody. Renal tissue was processed for light microscopy analysis, namely: a computer-aided morphometry of lysosomes in proximal tubular cells, a single-blind evaluation of gentamicin-induced tubular injury, the measurement of cell proliferation by immunocytochemical detection of BrdU-labeled nuclei, the demonstration of EGF-like immunoreactive material in renal tissue by using anti-rat EGF antiserum and immunogold-silver staining. As revealed by the morphometry of lysosomes in proximal tubular epithelium, the degree of gentamicin-induced phospholipidosis was maximum at day 1 (relative area occupied by lysosomes was increased 25-fold over mean control value) and declined thereafter. In contrast, tubular necrosis reached a peak 4 days after the end of drug administration. In proximal tubular epithelium, the stimulation of cell turnover associated with tubular regeneration showed a peak at day 7 (15-fold the mean control value). Tubular regeneration was also accompanied by mild interstitial hyperplasia. Three weeks after treatment with gentamicin, morphological evidence of drug-induced injury had disappeared due to the tissue repair process, except for the occasional presence of small hyperplastic foci in renal cortex interstitium. In both treated animals and controls, EGF immunoreactivity as revealed by immunocytochemical staining was associated with distal tubules (renal cortex and outer medulla).(ABSTRACT TRUNCATED AT 400 WORDS)


Activity of serum enzymes in puromycin aminonucleoside-induced nephrotic syndrome.

Total serum protein, serum albumin, total urine protein excretion, and the serum activity of several enzymes--aldolase (ALS), cholinesterase (CHS), leucine aminopeptidase (LAP), isocitrate dehydrogenase (ICD), aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase (HBD), creatine kinase (CK), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT)--were estimated in rats with nephrotic syndrome (NS) at 2, 4, 6, 8, 10, 12, 16, 20, and 30 days after a single injection of puromycin aminonucleoside (PAN). It was found that: (a) total serum protein and serum albumin diminished on day 4 and returned to control values on days 20 and 30, respectively; (b) total urine protein excretion rose on day 4, reached a peak value on day 8, and then fell substantially but still remained higher than control values on day 30; (c) ALS and CHS activities increased; (d) LAP, ICD, and AST activities showed a biphasic pattern, first increasing and then decreasing; (e) ALT, LDH, HBD, CK, and ALP activities decreased; and (f) GGT activity remained unchanged. The differences in the profiles of the enzyme activities suggest their independent regulation in experimental NS induced by PAN.


IgA nephropathy: acute renal failure, acute tubular necrosis, and features of postinfectious acute glomerulonephritis.

From 1976 to 1987 on our Nephrological Unit, 57 patients with IgA nephropathy (IgAN) proven by renal biopsies were found. Three of those presented with acute tubular necrosis (ATN) and glomerulitis, without extrarenal predisposing cause in two; and showed, as prominent manifestation, a severe acute renal failure syndrome (ARFS), needing dialytic treatment. All three had hematuria, which was macroscopic in two and microscopic in one. Thus the prevalence of the association of glomerulitis and ATN was about 5.2%. There was complete recovery of renal functions in all three patients, but the usual symptomatology of IgAN. Two patients presented polymorphonuclear neutrophils infiltration of glomerular capillaries and in one of them, electron-dense deposits on the epithelial side of glomerular basement membrane ("humps") were observed, as well as those identified in the mesangial area. The glomerular polymorphonuclear neutrophils infiltration and endothelial cells proliferation (cases 1 and 3), the presence of "humps" (case 1), high antistreptolysin O (ASO) titers (cases 1 and 2), and low serum complement levels (case 1), suggest the possibility that antigens able to cause postinfectious glomerulonephritis (streptococcal or not) could induce in some individuals, by another immunopathogenetic route, mixed histopathological and clinical features of IgAN and postinfectious glomerulonephritis.


Thrombocytopenia in renal failure in a developing country.

A retrospective study over a 3-year period was done looking at predialysis platelet levels, in particular, thrombocytopenia. Seventy-five patients with acute renal failure (ARF) and 75 patients with chronic renal failure (CRF), treated at King Edward VIII Hospital, were randomly chosen. Platelet counts were performed on a coulter counter (S + 2) and counts of less than 150 x 10(9)/L were considered as thrombocytopenia. Of the 75 CRF patients, 47 were males. Eleven (14.7%) were thrombocytopenic with a mean platelet count of 118.3 x 10(9)/L and a range of 83-146 x 10(9)/L. The mean creatinine level was 1510 micrograms/L. The remaining nonthrombocytopenic patients had a mean platelet count of 268 x 10(9)/L and a mean creatinine of 1080 micrograms/L. Of the ARF patients, 39 were males. Twenty-two (29.3%) had thrombocytopenia with a mean platelet count of 98 x 10(9)/L and a range of 22-147 x 10(9)/L. The mean creatinine level was 819 micrograms/L. The remaining nonthrombocytopenic patients had a mean platelet count of 319 x 10(9)/L and a mean creatinine of 1020 micrograms/L. In CRF patients no correlation was found between thrombocytopenia and the disease process. Creatinine levels appear to be higher in the thrombocytopenia group than in the nonthrombocytopenic group. In the ARF group of patients, females had a higher frequency of thrombocytopenia than males. Obstetrical and gynecological causes and herbal ingestion were the 2 major underlying etiologies in the thrombocytopenic group. Thrombocytopenia appears to be a common presenting feature in ARF as opposed to CRF, and this may be accounted for by the underlying etiologies in ARF.


Contrast media nephrotoxicity: comparison of diatrizoate, ioxaglate, and iohexol after intravenous and renal arterial administration.

In several studies in humans and animals it has been suggested that high osmolality and ionicity of contrast media are responsible for higher nephrotoxicity. To examine this suggestion, we evaluated the renal effects of three different contrast media--an ionic high osmolar, an ionic low osmolar, and a nonionic--following intravenous and renal arterial administration, in a population of 84 unselected, nondiabetic patients with adequate renal function. The results showed that the nephrotoxicity is minimal and equal for all three contrast media and for both routes of their administration, and it is concluded that in this category of patients the far higher cost of the newer low osmolar ionics and nonionics should be considered seriously in regard to nephrotoxicity.


Normal renin-aldosterone-insulin and potassium interrelationship in FMF patients and amyloid nephropathy.

The renin-aldosterone system and plasma insulin were studied in 19 patients with familial Mediterranean fever (FMF). Their relationships to serum potassium level at rest and before and after oral glucose loading are described. An interesting finding is the occurrence of hyperkalemia in the absence of oliguria, in the advanced stages of renal failure. No differences were found in the activity of the renin-angiotensin-aldosterone system to explain these variations in serum potassium found in some of the patients. The response of the renin-aldosterone system to glucose loading showed no abnormality, and the regular relationship between serum potassium, plasma renin activity (PRA), aldosterone, insulin, and plasma pH is maintained. Levels of insulin, potassium, and bicarbonate in serum or plasma pH were found similar in FMF patients with normal renal function with and without proteinuria. Further decrease in renal function due to the progression of the underlying disease is manifested by an increase in FENa+ and FEK+ and a hyperchloremic metabolic acidosis, as is the case in other patients with chronic renal failure.


Interleukin-2 deficit in hemodialysis patients. Role of prostaglandins.

Uremic patients suffer from various immunological alterations, whose pathogenesis is still unknown. Here, we studied 37 hemodialysis patients in order to investigate the role of prostaglandins (PGs) in uremic immunological deficiency, specifically in relation to interleukin-2 (IL-2) synthesis. We confirmed previous published data on deficient response to PHA in chronic renal failure patients (cpm, mean +/- SEM: 15,400 +/- 2,100 in uremics vs. 29,500 +/- 3,380 in controls, p < 0.04) and established a correlation between this deficiency and diminished IL-2 synthesis (r = 0.619, p < 0.05). The direct measurement of PGs in lymphocyte cultures showed greatly increased concentrations in the presence of uremic serum (US). We found that PGs synthesis can be inhibited by up to 80% if cultures are supplemented with indomethacin (IND--a cyclooxigenase inhibitor) or by removal of monocytes (producers of PGs). Both methods situated the uremic proliferative response within the normal range in cultures with FCS, and close to the normal range in cultures with US. We observed a deficit of IL-2 in hemodialysis patients (means +/- SD: 8,940 +/- 6,420 in uremics vs. 16,900 +/- 3,890 in controls). Addition of exogenous IL-2 normalized lymphocyte response even in US cultures, with no additive effect between PGs inhibition and exogenous IL-2 except in US cultures. It is suggested that IL-2 deficit of uremics depends, at least in part, on an increase in PGs synthesis induced by US.(ABSTRACT TRUNCATED AT 250 WORDS)


Performance characteristics of contemporary hemodialysis and venovenous hemofiltration in acute renal failure.

Modality choice in the treatment of acute renal failure (ARF) should be based on the match between individual patient needs and the characteristics of available therapies. Considerations include access, risk of bleeding, hemodynamic instability, and ability to remove excess volume. We prospectively studied 547 consecutive treatments for ARF in 110 patients to determine the performance features of modalities based on single-vessel venous access: hemodialysis (HD) and venovenous hemofiltration (VVH). All treatments were performed in an 18-month period at a single center. Patients' ages ranged from 16 to 84 years; 26 were trauma cases; 69 patients expired during their hospitalization. Mean number of treatments per patient was 4.97. Mean treatment duration was 197 min. Heparin was used unless active bleeding was present or felt to be a high risk; mean dose required was 2628 units. Pressor therapy was in progress prior to initiation of 260 (48%) of treatments. pretreatment and posttreatment mean systolic and diastolic BP were unchanged for the group. Forty-three (7.9%) treatments were terminated prematurely; of these only 27 (4.9%) were due to hypotension. No patient developed clinically apparent bleeding during any treatment. Contemporary equipment and techniques allow for provision of high-quality intermittent therapy for ARF, with excellent hemodynamic stability. Shorter, single-vein access treatments are advantageous for severely ill or injured patients who often undergo invasive monitoring and multiple studies or procedures.