[The behavioral characteristics of rats selected for their learning capacity]. Experiments were conducted in rat strains selected for high (KHA) and low (KLA) levels of the elaboration of conditioned reflex of active avoidance in shuttle box. KHA rats, as compared with the KLA ones, showed considerably higher indices of learning the shuttle avoidance, a greater number of intersignal runs during learning, a higher level of motor activity under open field conditions and its more marked extinction. These data point at the role of both associative and non-associative processes in the formation of active avoidance reflex. During 5 days of reflex training the rats of both strains retained a high level of defecation until the end of the test that pointed at the emotional strain unceasing in spite of the automatization of the reflex.


[The effect of hypothalamic stimulation on food choice with rats maintained on different water-salt rations]. Electrical stimulation of the lateral hypothalamus in rats induces an increase of water intake and decrease of thresholds of eaten salty food. These effects are displayed in control animals and under salt diet and water deprivation. The hypothalamus stimulation relaxes the effects of "psychic distillation" of food which occur during spatial coincidence of conditioned signal of insipid food with salty reinforcement. Besides, the trans-switching of signal significance of conditioned stimuli connected with insipid and salty reinforcements is accelerated. The electrostimulation of the hypothalamus accelerates the elaboration of conditioned aversion of salty food inhibition of conditioned runnings toward corresponding food-box, and intensifies the existent state of thirst transforming it in the dominant motivation.


[Trace rhythm recruitment by the neurons of the rabbit sensorimotor cortex in old age]. Spectral analysis (ACG and gSP) of the impulse activity of the neurones of the old rabbits sensorimotor cortex allowed to reveal a trace recruitment of the rhythm--CR analogue to time--in after-action f rhythmic stimulation. Connection was established between the number of presented series of periodic electrocutaneous stimulation and expressiveness of the trace rhythm recruitment depending on the animals age. Trace rhythm recruitment took place slower in old animals (54-56 months) than in young ones (up to 1 year), chiefly in 2-3 experimental days after 2-4 series of rhythmic stimulation and was preserved in a small percent of cases the next day after stimulation. In the background activity of a number of neurones an initial periodicity was discovered, which was intensified under the influence of stimulation by another frequency, or the initial rhythm was extinguished, and stimulation rhythm was reproduced. Periodical stimulation in very old animals (66-85 months) practically did not evoke plastic reconstructions of the cortical neurones. Under the influence of the stimulation a non-specific trace increase of the frequency of neurones background activity of the old animals was observed. The revealed characteristics of plastic neurones properties may testify to projected disturbances of mnestic processes at definite age stages of normal aging.


[The activity of Krebs cycle enzymes in the visual analyzer of normal rats and under stress]. In the visual analyzer of the intact animals higher activity of NAD-dependent dehydrogenases of tricarbonic acids cycle is observed in the retina and of FAD-dependent dehydrogenases in the occipital brain lobes. The influence of stress by Desiderato method elicits compensatory increase of the succinatedegidrogenase activity. The acute stress elicits a change of regulation of the activity of dehydrogenase of tricarbonic acids cycle, estimated by the reaction to functional load. Animals staying in the darkness after stress promotes restoration of the tricarbonic acids cycle of the enzymes activity up to the normal level.


[A spectral-correlational analysis of the electrical activity of the sensorimotor cortex and the internal geniculate body during a motor-polarization dominant]. By spectral-correlative analysis the dynamics was studied of structural changes of coherent relations of the electrical activity of the sensorimotor cortex and medial geniculate body (MGB) of the rabbit under motor polarization dominant created by the action of DC anode on the sensorimotor cortex area. It was shown, that in the power spectra of the MGB, besides the increase of the delta-region components in interstimulus intervals at the dominant, during the action of the sound stimulus a distinct maximum appeared in the alpha-rhythm range of the electrical activity of MGB of the "dominant" hemisphere. The coherence increase of the delta-range of the MGB and the sensorimotor cortex electrical activity in the "dominant" part of the brain was manifested exclusively in the period of sound stimulus action.


[Biogenic amines in the brain structures of rats from genetically diverse strains under stress]. The content was studied of biogenic amines and their metabolites (by the method of high-effective fluid chromatography electrochemical detection) in the reticular formation of the midbrain, locus coeruleus and sensorimotor cortex in the rats of Wistar and August lines, differing in the behaviour in the open field, in conditions of immobilization stress. The dependence was revealed of the biogenic amines level on the animals genotype and individual characteristics. Most probably, the level of biogenic amines metabolism in central brain structures determines the stability of the animals against emotional stress.


[The effect of the deprivation of the paradoxical sleep stage on the temporal dynamics of swimming in rats with antidepressive and depressant exposures]. After REM sleep deprivation the time-course of the forced swimming was reorganized. As shown, reduction of rhythmical index of depression, such effect has an antidepressive nature. In this model potentiation of specific activity of antidepressant imipramine and attenuation of depressive properties of clonidine were observed. These results suggest that shifts in sleep phase structure may be a source of restriction of circadian desynchronosis, upon which depression is based.


[The dynamics of the brain heat fields of rats in the late postresuscitation period during stress]. By thermoencephaloscopy method the temperature relief of the rats cerebral cortex was studied after the clinical death and reanimation. The rehabilitation of the animals neurological status was completed in 1-2 days. In the remote postresuscitation period (up to 2 months), expressed disturbances were revealed of the background thermomaps and of thermal reactions of the cerebral hemispheres, evoked by the stress influence. Pathologic mosaics of thermal characteristics was revealed in conditions of relative rest and disturbance of dynamics of the brain temperature reactions and the character of interhemispheric asymmetries at stress influence. Individual character is pointed out of postreanimative pathology, which is manifest both in the background thermomaps and after the functional load. The results of the studies suggest the importance of individual approach in rehabilitation therapy of postreanimative disease.


[Intracellular messengers and their roles in retinal gap junctions]. Intracellular injection of cAMP or cGMP into retinal horizontal cells blocked the gap junctions between the cells. Similar results were obtained when L-arginine was injected into the cells. L-Arginine is a substrate of nitric oxide (NO) which is believed to activate soluble guanylate cyclase to produce cGMP. The endothelium-derived relaxing factor (EDRF) in the blood vessels has been identified as NO. With respect to the nervous systems, production of NO and its synthase have been found in the brain, and NO has been discussed in relation to such phenomena as synaptic plasticity, long-term potentiation, and development. The decoupling effect of L-arginine suggests the presence of the L-arginine: NO: cGMP pathway in the retina as well. Before injection of cAMP, cGMP or L-arginine, the applied current leaked through the gap junctions. After the injection, the horizontal cells could be easily polarized by intracellular current injection, and the synaptic mechanisms were analyzed by measuring I-V curves. In luminosity-type (H1) horizontal cells, the reversal potential of light responses was estimated at about 0 mV. In addition, conductance decreases were detected during illumination. These findings support the widely accepted hypothesis that glutamate is released from the photoreceptors in darkness. In chromaticity-type cells (H2 and H3 cells), the reversal potentials of light responses were about 0 mV, suggesting that the ionic mechanisms of synaptic transmission are common among horizontal cell types.


[Effects of agonists and antagonists of benzodiazepine, GABA and NMDA receptors, on caffeine-induced seizures in mice]. In mice, tonic convulsive seizure induced by intravenous administration of caffeine (adenosine A1, A2 receptors antagonist) was significantly potentiated by any one of L-PIA (adenosine A1 receptor agonist), NECA (adenosine A2 receptor agonist) and 2-ClAd (adenosine A1, A2 receptors agonist). The caffeine-induced seizure was unaffected by diazepam (benzodiazepine receptor agonist), but was inhibited by Ro 15-1788 (antagonist or partial agonist). beta-DMCM (antagonist or inverse agonist) increased the seizure. Muscimol (GABA-a receptor agonist), baclofen (GABA-b receptor agonist) and AOAA (GABA transaminase inhibitor) did not show significant effect on caffeine-induced convulsion. Bicuculline (GABA-a receptor antagonist) and picrotoxin (chloride channel blocker) significantly potentiated the convulsion at the doses which did not induce it. Caffeine-induced convulsion was potentiated by NMDA with its non-convulsive dose. CPP (competitive NMDA receptor antagonist) and MK-801 (non-competitive NMDA receptor antagonist) significantly inhibited the seizures. These results suggest that caffeine-induced seizure is not caused by blockade of adenosine receptors. Caffeine may act to beta-carboline sensitive benzodiazepine receptor (Type 1) which has no linkage with GABA-a receptor. Furthermore, it is implied that caffeine plays some role at NMDA receptor calcium ion channel complex.


[The diagnostic value of serum hormone parameters in hirsutism]. In 46 patients showing mild or moderate hirsutism, and 49 age-matched regularly menstruating women without symptoms the following hormone and protein serum levels were measured: Total testosterone (T), free testosterone (fT), dehydroepiandrosterone sulfate (DHEAS), androstendione (ASN), sex hormone binding globulin (SHBG), free androgen index (FAI) as expressed by the T/SHBG ratio, cortisol, Prolactin (PRL), LH/FSH ratio, 3 alpha-androstanediol glucuronide (ALG), basal and poststimulated 17-hydroxyprogesteron (17OH-P) and (in some cases) basal and poststimulated 11-deoxycortisol (S). The study was designed for exploring the diagnostic significance of these parameters and evaluating the extent to which they contribute in establishing the source of hyperandrogenism. The mean values of all but one (PRL) of the hormone and protein levels varied significantly from the controls, T, DHEAS, FAI and ALG showing the greatest differences. Most frequently elevations of T, DHEAS, and FAI values were established, the levels of which exhibited a highly significant correlation. In 96% of the hirsute women the elevation of 1 to 3 of these parameters was demonstrated. FAI was shown to be associated with a higher diagnostic accuracy than did SHBG or fT. In 9/43 patients increased values of ALG were found, which as an important metabolite of dihydrotestosterone reflects peripheral androgen activity, particularly of the skin. In every case these abnormal values were combined with elevated levels of other androgens (T, DHEAS, ASN). It is concluded from these limited data that an isolated elevation of ALG due to primary accentuation in 5 alpha-reductase is a rare or even non-existing occurrence.(ABSTRACT TRUNCATED AT 250 WORDS)


[New methods for diagnosing infection in pregnancy]. Maternal infections during pregnancy are of special relevance because of the risk of transmission to the fetus. Besides serological methods of diagnosing acute maternal infection, new approaches to assess fetal involvement have been made by invasive procedures, such as ultrasound-guided fetal blood sampling or amniocentesis. The most relevant infections in pregnancy are briefly reviewed with their incidence, consequences of fetal infection, and standard diagnostic procedures. Immunological methods are handicapped by the immaturity of the fetal immune system; direct culture is complicated and time-consuming. The application of molecular biological methods to directly identify the RNA- or DNA-sequences of the infectious agent may be an alternative. Two methods, polymerase-chain-reaction (PCR) and in-situ hybridization (ISH) are explained. Broad clinical use is still hindered by problems in specificity and quantitative accuracy. Nevertheless, successful diagnosis of most of the relevant infections in pregnancy by these molecular biological methods, is published, and discussed in a review of the recent literature.


[Optimization of an enzyme immunoassay for the detection of antibodies against avian reoviruses--with special consideration of the calculation of results and test interpretation]. Selected steps in the establishment of an enzyme-immuno-assay (EIA) are shown with an EIA for detection of antibodies against avian reoviruses of chicken. The centre of this work is to show the various possibilities of calculation and interpretation of the test results. The definition of the cut-off-value is the basis for the interpretation of the assay and the consequences for the veterinarians in the field and the animal owners. Basic parameters (sensitivity, specificity, predication value, prevalence) of the test validation are discussed with the example of the examination of a new hen flock in the EIA, compared to serum neutralisation test.


Hematological parameters and visceral lesions relationships in rabbit viral hemorrhagic disease. Twenty rabbits were inoculated with a suspension of Viral Hemorrhagic Disease virus. Hemostatic functions were assessed every sixth hour from 6 to 60 hours post-inoculation. Tissue samples obtained at the same intervals allowed the study of the development of lesions throughout the experiment. Biological signs of Disseminated Intravascular Coagulation (DIC) were detected on and after 30 h post-inoculation and consisted of prolonged One Stage Prothrombin Time and Activated Partial Thrombin Time, the decrease of factors V, VII, and X and high levels of soluble fibrin monomer complexes and D-dimers. A reduction of thrombocyte numbers, heterophils and lymphocytes was associated. The close association of DIC and necrotizing hepatitis lesions suggested the hepatic lesions to be the most important DIC triggering factor. Other mechanisms are discussed.


Papillomavirus infection in greenfinches (Carduelis chloris). The present report describes transmissible papillomatous digital lesions observed in two greenfinches (Carduelis chloris) living in a private aviary. The disease appeared in the male bird and successively in the female but did not affect other passerine and psittacine species living with the sick birds. Negative contrast electron microscopy revealed the presence of 52.6 nm virus particles similar to papillomavirus. Immunoelectronmicroscopy confirmed the presence of Papillomavirus genus specific structural antigens in the virus observed.


An antigen capture test for the detection of cattle viremic with bovine viral diarrhoea virus--a comparison with BVD virus isolation from buffy coat cells in bovine kidney cells. An antigen capture enzyme immunoassay (EIA) for the detection of bovine viral diarrhoea (BVD) viral antigen in peripheral blood lymphocytes of cattle was used for the screening of 241 animals. The test used a monoclonal antibody directed against a conserved antigenic domain of a nonstructural protein (p125/p80) of pestiviruses for antigen capture. Bound antigen was detected with a pestivirus-specific polyclonal peroxidase conjugate. In parallel the samples were analysed by routine virus isolation procedures based on cell culture. Virus isolation and antigen capture EIA were positive in 54 cases. The latter test scored one additional sample.


[The role of the food transmission factor in the occurrence of 2 hepatitis A outbreaks]. Two outbreaks of virus hepatitis were etiologically and epidemiologically interpreted. In this work the original method of obtaining washings, with their subsequent concentration, from the suspected foodstuff was used and hepatitis A virus was then detected in concentrated washings in the enzyme immunoassay, which made it possible to confirm the contribution of the alimentary factor of the transfer of infection (sun-cured melon) in the above-mentioned outbreaks. The data thus obtained are indicative of the necessity to conduct epidemiological investigation, taking into account the possibility of contacting hepatitis A when using foodstuffs not subjected to preliminary treatment.


Effect of systemic lidocaine on dorsal horn neuron hyperactivity following chronic peripheral nerve injury in rats. Systemic lidocaine (3-4 mg/kg) was tested for its effect on identified spinal cord wide-dynamic-range (WDR) neurons in rats with a unilateral chronic neuropathy induced by two different peripheral nerve injuries (section or compression by ligatures). In both cases, neurons on the side ipsilateral to the injuries showed a spontaneous firing frequency higher than that of the opposite intact side (23.5 +/- 3.4 vs 4.2 +/- 1.5 spikes/sec). The hyperactivity was not affected by a sensory block of the peripheral receptive field. It was consistently found that lidocaine suppressed or reduced the spontaneous neuronal hyperactivity on the ipsilateral side, whereas it had no effect on the normal spontaneous activity of the neurons on the intact side. In all recordings, the hyperactivity returned to the prelidocaine injection rates within 20 min. These results indicate a preferential action of subanesthetic doses of lidocaine on the hyperactive WDR neurons. Such preferential action is related to a susceptibility acquired by WDR neurons of the peripherally injured side and is not simply attributable to the increased frequency of firing.


Visceral and cutaneous leishmaniasis in an European paediatric population. Six children with leishmaniasis, aged 10 months to 10 years, were treated in the Paediatric Department. Four patients had visceral leishmaniasis (kala-azar): diagnosis was based on bone marrow examination and therapy consisted of a combination of Glucantime and Lomidine. The remaining two children had cutaneous leishmaniasis: diagnosis was made by skin biopsy and the patients were treated with Glucantime alone. In all children, serology was clearly positive at the time of the diagnosis and all patients improved. The only side effects were cough associated with fever in one child, and supraventricular premature beats in another one. They were ascribed to Glucantime, and proved reversible after discontinuation of the treatment.


[Nonbacterial thrombotic endocarditis. Case report and literature review]. Nonbacterial thrombotic endocarditis is the most prevalent endocarditis at autopsy. It is a clinically important cause of arterial embolisation. Often it is observed in association with malignancy (mainly gastrointestinal adenocarcinomata), severe infections and other fulminant acute disease processes. A deranged or damaged valvular surface and clotting disorders are important pathogenic factors. The valvular vegetations are pathologically characterized by a bland, fibrin-platelet thrombus; they usually affect the mitral and aortic valve. Neurologic events are the most common clinical manifestations, but any organ may be involved by emboli. The association of venous and arterial thromboses and pulmonary thromboembolism underscores the pathogenetic role of hypercoagulability in the development of nonbacterial thrombotic endocarditis. The clinician must be a vigilant observer in order to make the antemortem diagnosis. If possible, the underlying process should be treated; anticoagulation therapy with heparin sometimes is helpful.


Clinical use of aztreonam in a psychogeriatric population. Aztreonam is a safe, well-tolerated antibiotic with a good response in psychogeriatric patients. The combination of aztreonam with flucloxacillin is an acceptable first-choice treatment for severe infections in psychogeriatric patients.


The role of percutaneous transvenous balloon mitral valvuloplasty in the treatment of patients with symptomatic mitral stenosis. Since its introduction in 1984, percutaneous transvenous mitral balloon valvuloplasty (PTMV) has emerged as an effective technique in the treatment of selected patients with severe mitral stenosis. The most important factors determining the haemodynamic and clinical outcome after PTMV are the anatomic and pathological features of the mitral valve apparatus. In patients with pliable, non-calcified valves, immediate success rates of well over 90% are achieved. Short-term follow-up studies of such patients after PTMV demonstrate a low rate of valve restenosis, with the vast majority of patients remaining much improved clinically. Less favourable immediate and short-term results are observed in patients who have non-pliable, calcified valves. Major acute complications of PTMV include thromboembolic events and the production of severe mitral regurgitation. It appears that, as a result of increased operator experience, better patient selection and refinements in the technique of PTMV, the rates of these acute complications are now very low. Follow-up studies will be needed to assess the long-term efficacy of the procedure. The first publications on this field are encouraging.


[Fetal alcoholism syndrome: apropos of a case]. Fetal alcoholic syndrome (F.A.S.) is a well-recognized entity for over 20 years; it associates mental retardation, delayed growth and anomalies of the cranium in children born from alcoholic mothers. The syndrome has been described primarily in young children. By contrast, its evolution is not well known. We report the case of a 15-year old youngster, who exhibited the characteristic features of F.A.S. We also review the data related to the clinical and pathophysiologic aspects of the syndrome.


Pott's tuberculous spondylitis in Belgium 1990. A 23-year-old man is described with tuberculous spondylitis and paravertebral abscedation (Pott's disease). This is one of the rare cases of Pott's disease in a patient coming from industrialised Belgium, not belonging to one of the known risk groups such as intravenous drug users, immunodeficients or immigrants from southern countries. The epidemiology, differential diagnosis, complications and therapy are briefly discussed.


Acute phosphine poisoning? A case report and review. A case compatible with an acute phosphine poisoning after inhalation is presented. The observation was notably characterized by necrosis of the nasal mucosa, the delayed onset of a pulmonary edema and myocardial injury with multisystemic involvement. A review of literature, not very prolific in this field, is included in the discussion.


In vitro effects of tumor necrosis factor-alpha on human thyroid follicular cells. Tumor necrosis factor-alpha is assumed to be an important mediator in thyroid autoimmunity. In the present study we have shown that human thyrocytes possess a single specific binding site for recombinant tumor necrosis factor-alpha with an average of 9,300 receptors/cell (Kd = 1.9 x 10(-10) mol). The effects of the cytokine on thyroid cell proliferation were assessed by 3H-thymidine uptake as well as by the protein and DNA content of cell monolayers. Low dose tumor necrosis factor-alpha resulted in a moderate stimulation of cell proliferation with an increase of 3H-thymidine incorporation from 44,613 +/- 7,989 cpm under basal conditions to 63,326 +/- 6,822 cpm after 100 U/l tumor necrosis factor-alpha (p < 0.01). Higher doses of the cytokine were less effective. On average, bTSH stimulated cAMP production of human thyrocytes was significantly augmented after preincubation with recombinant tumor necrosis factor-alpha. The maximum effect was observed after 1,000 U/l tumor necrosis factor-alpha (281.5 +/- 107.0 vs 114.5 +/- 33.6 fmol cAMP/micrograms protein under basal conditions: p < 0.05), whereas higher doses of the cytokine were again less effective. This phenomenon could at least partly be explained by a cytokine-mediated downregulation of tumor necrosis factor-alpha binding. We conclude that in vitro tumor necrosis factor-alpha modulates in addition to its well known synergistic effect on interferon-gamma induced HLA class II expression the function and proliferation of human thyroid follicular cells as well. These effects are mediated via specific cell surface receptors.


Possible involvement of leukotrienes in human luteal function. The present study was undertaken to assess the ability of human corpora lutea to produce leukotriene B4 (LTB4). The maximum capacity of luteal cells to secrete progesterone was attained on day 4, and both the basal production and the responsiveness to hCG decreased thereafter. In contrast, the production of LTB4 by cultured luteal cells was significantly reduced on day 4, but increased thereafter. The basal concentration of LTB4 produced by luteal cells varied from 75 to 590 pg/10(5) cells/2 days. LTB4 production appeared to decrease concomitantly with increased-progesterone production in cultured luteal cells. Exposure to hCG decreased significantly LTB4 production by cultured luteal cells on day 4. An inhibitor of the lipoxygenase pathway, nordihydroguaiaretic acid (NDGA), inhibited LTB4 production in a dose-dependent manner. However, NDGA did not affect basal progesterone production by the cultured luteal cells. A significant inverse relationship existed between the accumulation rates of progesterone and LTB4 in the luteal cells. Furthermore, the addition of LTB4 inhibited progesterone production in a dose-dependent manner in both the presence and absence of hCG. In conclusion, LTB4 could be synthesized by human corpora lutea in vitro, and correlated inversely with the secretion rates of progesterone. These data suggest that LTB4 produced locally in the corpus luteum may be an important regulator in human luteal regression.


Parathyroid hormone degradation by opossum kidney cells via receptor-mediated endocytosis and lysosomal hydrolysis. The mechanisms involved in parathyroid hormone (PTH) degradation by proximal renal tubule cells were studied using an opossum kidney cell line possessing PTH receptors as an in vitro model system. One hour incubation of 5 nmol/l human (h) PTH-(1-84) with intact opossum kidney cells (4.0 x 10(6) cells) resulted in about 70% degradation and disappearance of hPTH-(1-84) from the medium, as determined by a two-site immunoradiometric assay. Preincubation with 100 nmol/l h[Nle8, Nle18, Tyr34]PTH-(1-34)amide for 6, 24, 48 and 72 h caused a 26, 47, 62 and 73% decrease, respectively, in PTH degradation by opossum kidney cells. Binding studies with 125I-labeled h[Nle8,Nle18,Tyr34]PTH-(1-34)amide as a radioligand showed that PTH receptor binding decreased with the time of pretreatment with the agonist. Pretreatments of the cells with monensin, an inhibitor of endocytosis, and the lysosomotropic agents such as chloroquine, ammonium chloride and leupeptin, inhibited degradation of hPTH-(1-84) by 87, 71, 76 and 72%, respectively. Concentrations of 5 nmol/l hPTH-(39-84) and hPTH-(39-68), which are known not to bind to PTH receptors appreciably, were not degraded by opossum kidney cells during 1 h incubations. Thus intact, biologically active PTH, but not its inactive fragments, is degraded by opossum kidney cells, by receptor-mediated endocytosis and lysosomal hydrolysis. A mechanism resembling the peritubular uptake of intact PTH by perfused kidneys reported previously appears to play a main role in PTH metabolism by cultured renal cells.


Effects of wheat bran on blood and tissue hormone levels in adult female rats. The protective effect of dietary fiber on breast cancer development might be explained by the interaction between dietary fiber and hormonal processes. We studied the effects of dietary fiber and the effects of a reduced energy intake on the exposure of mammary tissue to both estrogens and progesterone, as well as the blood plasma levels of these steroids and of LH and FSH. Adult female Fisher rats were fed ad libitum either a low-fiber diet (0.5% dietary fiber based on wheat flour) or a high-fiber diet (9.2% dietary fiber based on wheat bran). A third group was used to control for the reduced energy intake of the high-fiber group and was fed the low-fiber diet restricted. Energy intake was similar for the second and third groups. Four out of 14 rats of the high-fiber group and 4 out of 15 rats of the restricted low-fiber groups were not in cycle after seven weeks on the experimental diets, indicating that the estrous cycle was significantly affected by a reduced energy intake. Exposure of mammary tissue to estrogens did not differ among the groups, as measured by estrone, estradiol-17 beta, estriol and peroxidase activity. During the peak period, plasma LH levels were significantly higher in the high-fiber group than in the two low-fiber groups. FSH and progesterone plasma levels were unaffected by the experimental diets. It is concluded that dietary fiber affects the hormonal processes involved in breast cancer development. The increased LH levels indicate an increased estrogen production in the ad libitum high-fiber group.


Clinical significance of the venous occlusion test on systemic lupus erythematosus patients with a focus on changes in blood levels of tissue plasminogen activator, von Willebrand factor antigen, and thrombomodulin. We investigated the clinical significance of the venous occlusion (VO) test on patients with systemic lupus erythematosus (SLE) with or without circulating lupus anticoagulant (LA) concerning whether changes in the blood coagulation and fibrinolysis system in vivo subsequent to VO reflect mechanical stimulation of the endothelium or presence/development of endothelial damage. The tissue plasminogen activator antigen (tPA:Ag) before VO was much lower in the LA-positive patients than in the LA-negative ones (p < 0.01) and the von Willebrand factor antigen (VWF:Ag) pre-VO was significantly higher in the patient group, regardless of LA status, than in the control group (p < 0.01). But the mean increment in tPA:Ag and VWF:Ag post-VO, when expressed as the percentage of the baseline level, showed no appreciable difference between LA-positive and -negative groups. Thrombomodulin (TM) basically, on the other hand, was higher in the patients of either LA status than in the controls (p < 0.01) with a significant post-VO increase in the SLE group, which was more marked in the LA-positive patients, against no substantial change in the controls (p < 0.01). It is known that tPA and VWF:Ag are released simply as a result of endothelial stimulation and that the release of TM is preceded by endothelial damage. Based on the present results, we may well conclude that (1) the endothelium is functionally intact in SLE patients, (2) an injury of the endothelium, possibly as a consequence of vasculitis, preexists in LA-positive patients, and thus to measure the TM response to VO would offer a helpful tool in diagnosing the preexisting endothelial damage in these clinical settings.


Sex differences in adrenocortical structure and function: 29. Morphometric and functional studies on the effects of gonadectomy and gonadal-hormone replacement on the hamster adrenal cortex. The morphologic changes evoked in the adrenal glands of male and female hamsters by gonadectomy (15 weeks) and gonadal-hormone replacement (single s.c. injection of 5 mg/100 g b.w. testosterone or 0.5 mg/100 g b.w. estradiol, 2 weeks before the sacrifice) were investigated by morphometric techniques and correlated with the functional alterations of the hypothalamopituitary-adrenal axis. Our findings evidenced a stimulatory role of androgens and a moderate inhibitory one of estrogens on the growth and steroidogenic capacity of the adrenal glands in male and female hamsters, respectively. Moreover, they suggest that these adrenal effects of gonadal hormones are, at least partly, independent of alterations in the pituitary ACTH release.


Postischemic alterations of complex spike cell discharges and evoked potentials in rat hippocampal CA1 region. Postischemic alterations of spontaneous discharges of complex spike cells (CS cells) and evoked potential in the rat hippocampal CA1 region were studied. Following 5 min of ischemia, CS cell discharge reappeared approximately 5 min after reperfusion and the frequency remained low, reaching a final value of 66.1 +/- 16.0% (n = 11) of preischemic frequency 2 h later. However, only one of 7 CS cells subjected to 20 min of ischemia exhibited discharges 2 h later. In the group with 5 min of ischemia, we obtained CS cell discharges from all rats at both 1 and 2 days after ischemia, with cluster frequencies indistinguishable from preischemic levels. In the group with 20 min of ischemia, discharges were noted in 7 neurons of 11 rats after 1 day, and in only 2 neurons of 8 rats after 2 days: their mean frequencies were lower than preischemic levels. In experiments of evoked potentials, the mean percentages of amplitudes of the post-synaptic potential (psp) 2 h after 3, 5 and 20 min of ischemia were 98.0 +/- 10.7 (n = 8), 70.7 +/- 8.22 (n = 9) and 45.1 +/- 6.34% (n = 7) of preischemic amplitudes, respectively. These results suggest that the functional deterioration of spike generation, as well as synaptic transmission, starts during transient ischemia and/or at the early stage of reperfusion.


Argyrophilic glial intracytoplasmic inclusions in multiple system atrophy: immunocytochemical and ultrastructural study. Argyrophilic intracytoplasmic inclusions in oligodendrocytes (AGCIs) were seen in all of 15 cases of multiple system atrophy (MSA), and none in other neurodegenerative diseases, including 9 cases of Menzel-type olivopontocerebellar atrophy and 4 cases of Joseph's disease. The inclusions were widespread, not only in the olivopontocerebellar and striatonigral systems but also among fibers connecting their affecting lesions of MSA. Immunohistochemically, they were closely associated with tau, tubulins and microtubule-associated protein 5. Ultrastructurally, they consisted of 30- to 50-nm filaments (not tubules) and electron-dense granules, in varying proportions, and their formation is discussed. The specific occurrence of AGCIs could be a key to approach the pathogenesis of MSA.


Determination of the early age of onset of equine recurrent laryngeal neuropathy. 2. Nerve pathology. The left and right recurrent laryngeal nerves and peroneal nerves from two groups of foals, one less than 1 month of age and the other 6 months of age, were examined by light and electron microscopy. While there was no evidence of fiber loss on light microscopy, occasional onion bulbs, regenerating clusters and swollen axons were seen in the recurrent laryngeal nerves. To quantitate these changes, total counts of the main pathological structures were performed using the electron microscope. In all the foals the most common abnormality seen in the laryngeal nerves were Bungner bands, which were most numerous in the left recurrent laryngeal nerve of the older group of foals. Swollen axons which contained accumulations of organelles were seen in both age groups but were more common in the older foals. Likewise, onion bulbs were more frequent in the older animals but were also seen as well-formed structures in a foal less than 2 weeks of age. These findings confirm the previous report of neurogenic changes in the laryngeal muscles of foals and suggest that recurrent laryngeal neuropathy has an early and possible prenatal onset in the horse.


Primary immunodeficiency diseases and Epstein-Barr virus-induced lymphoproliferative disorders. Increased incidence of malignant disorders is noted in patients with both primary and acquired immunodeficiency diseases. The pathogenetic mechanism(s) for these disorders remain unclear. Defective immunosurveillance of these patients, however, is mainly postulated to be responsible for the increased risk of these malignant disorders. Of the malignant disorders, Epstein-Barr virus (EBV)-induced lymphoproliferative disorders (LPD) have been increasingly reported, possibly due to improved therapeutic management techniques such as bone marrow transplantation, which results in prolonged survival periods for the primary immunodeficiency; the dramatic development of immunosuppressive treatments for transplant recipients; and the growing numbers of acquired immunodeficiency syndrome (AIDS) patients. This review focuses on the primary immunodeficiency diseases and EBV-induced LPD, and discusses pathogenetic mechanism(s) for the increased incidence of these malignant disorders.


Persistently high antibody titers and deficient specific cellular immunity to varicella-zoster virus in a retarded patient after varicella infection. We report on a 19 month old female who has been retarded developmentally after a severe varicella infection contracted from her mother 4 months after delivery. Her titer of varicella-zoster virus (VZV) IgG antibody has been remarkably high for 4 years after the infection. Natural killer activity and the specific cellular immunity to VZV, as tested by delayed type hypersensitivity skin test and lymphocyte-proliferation assay, were impaired. She had an improvement of ataxia and then progressed developmentally after administration of an anti-viral agent. Administration of oral corticosteroids and methylprednisolone transiently decreased titers of VZV antibody and, contrary to previous reports, returned natural killer activity to normal levels. We suggest that this case may be a persistent VZV infection similar to congenital cytomegalovirus infection due to selective defects in cellular immunity including NK cells. Whether this specific deficient cellular immunity is genetically determined or secondary to the viral infection is speculative. This is the first known report of such a case.


Malignant myoepithelioma of minor salivary gland origin. Myoepithelial cells are a significant component of most types of salivary gland tumors. A small but increasing number of case reports have also shown that true myoepithelioma (ME) forms a distinct clinicopathologic entity of salivary gland tumors with unique histologic features, however, the malignant type of ME is exceedingly rare. The present paper reports a case of malignant ME originating from the palatal minor salivary gland. The patient was a 70-year-old Japanese male with recurrent tumor of the palatal region. Pathologically, the tumor consisted of proliferating polygonal-shaped cells and plump spindle cells with cellular atypia and frequent mitoses, forming lumen-less lobuli or strands. Clear tumor cells were also found in part. The stroma was poorly developed without any myxoid or chondroid features. Immunohistochemical study showed positive stainings for S-100 protein, actin and vimentin in the tumor cells. Ultrastructurally, tumor cells had features of myoepithelial cells.


Signet ring cells in breast carcinoma. An immunohistochemical and ultrastructural study. Two cases of breast carcinoma composed predominantly of neoplastic cells with a signet ring appearance, one a case of invasive lobular carcinoma (ILC) and the other a case of invasive ductal carcinoma (IDC), were examined electron microscopically and immunohistochemically. In signet ring cells in the ILC, mucin was demonstrated ultrastructurally in the intracytoplasmic lumina and also to a small degree in the cytoplasmic mucous granules, whereas in signet ring cells in the IDC, mucin was found only in the cytoplasmic mucous granules. Immunohistochemically, signet ring cells in the ILC were intensely positive for gross cystic disease fluid protein (GCDFP-15), but those in the IDC showed no immunoreaction for GCDFP-15. Thus ultrastructural features and GCDFP-15 immunoreactivity appear to be useful for distinguishing between the two different types of signet ring cells.


[Effects of Cu2+ on the neuromuscular junction transmission]. Experiments were carried out on the isolated rat phrenic nerve diaphragm preparations and chick biventer cervicis preparations. Cu2+ at cumulative concentrations inhibited muscle contractile response to indirect stimulation without affecting the conductivity of the nerve. The inhibiting action of Cu2+ on the muscle contractile response to indirect stimulation was stronger than that to direct stimulation. Cu2+ did not affect the Ach sensitivity of the chick biventer cervicis muscle. The effects of Cu2+ on neuromuscular transmission were antagonized by Ca2+ and L-cysteine. It is concluded that Cu2+ produces neuromuscular blockade by acting mainly on the presynaptic nerve terminals, binding with the -SH groups of the membrane and thus altering the transmembrane movement of Ca2+ and reducing the release of Ach from the nerve terminals.


cAMP promotion of osteoclast-like cell development from mouse bone marrow cells requires a permissive action of 1,25-(OH)2D3. Recruitment of osteoclasts from monocytic precursors is modulated by local signals. We previously showed that monoblastic differentiation in U937 cells is stimulated by 1,25-(OH)2D3 and cAMP in series. We investigate here the combined effects of these agents to stimulate differentiation of osteoclast-like cells from mouse marrow. Cells from mouse marrow were harvested and cultured in alpha-MEM with 10% fetal bovine serum. The appearance of tartrate-resistant acid phosphatase-containing multinuclear cells was measured after 8 days in culture by cytochemical staining. Continuous exposure of cultures to 10 nM 1,25-(OH)2D3 positively stimulated development of these cells after 8 days (101 +/- 3 cells per well, n = 74). No osteoclast-like cells were found when 1,25-(OH)2D3 was added for the first 4 days followed by 4 days more with no treatment. PGE2 (1 microM) as a single agent added during the last 4 days of culture was not able to recruit osteoclast-like cells. However, cultures exposed to 1,25-(OH)2D3 during the first 4 days and 1 microM PGE2 during the second 4 days developed osteoclast-like cells at 8 days [66 +/- 8% of the formation seen with 1,25-(OH)2D3 alone, p less than 0.05]. Dibutyryl cAMP (1 microM to 3 mM) was also not effective used as a single agent, but was able to stimulate formation of TRAP-positive multinuclear cells when 1,25-(OH)2D3 preceded its addition to culture medium. cAMP analogs therefore mimicked the effect of 1 microM PGE2, but these experiments do not allow us to assign the PGE2 action entirely to activation of cAMP second messenger.(ABSTRACT TRUNCATED AT 250 WORDS)


Maturation-associated changes in the cellular composition of mouse calvariae and in the biochemical characteristics of calvarial cells separated into subclasses on Percoll density gradients. The effects of tissue maturation on the cellular composition and biochemical characteristics of bone were studied in neonatal, young adult, and aging mice. Osteoblast subclasses were isolated on Percoll density gradients. Neonatal calvariae consisted almost exclusively of cells banding at low and intermediate buoyant density. High buoyant density cells constituted 5-10% of total cells at 10 days of age but increased to 50-60% by 5 weeks of age. These latter cells were released late during collagenase digestion. This indicates that they arise from the deeper layer of bone. For this reason, we consider them putative osteocytes. We established that constitutive secretion of IGF-I and TGF-beta and activities of cellular alkaline phosphatase paralleled those of the tissue of origin in all cell groups and was highest in cells of intermediate buoyant density. These activities declined rapidly after cessation of growth at 5 weeks of age in both bone and isolated cells. Between 5 and 8 weeks of age, the hormonal response to PTH also declined dramatically. The maximum cAMP induced by PTH declined by about 70% in highly responsive cells of intermediate buoyant density and fell to insignificant levels in cells of high buoyant density. We found that a cyclic AMP response to PTH was positively correlated with stimulated secretion of IGF-I by this hormone in cells from animals of all ages. Despite their inability to respond to PTH with increases in cAMP and IGF-I, adult bone cells of high buoyant density continued to respond to PTH with increases in the secretion of TGF-beta.(ABSTRACT TRUNCATED AT 250 WORDS)


Estrogen and progesterone replacement therapy reduces glucocorticoid-induced bone loss. This is a retrospective study of 15 postmenopausal or amenorrheic women aged 34-78 years who had taken prednisone for 6-108 months and were followed for 1 year while continuing to take doses of 5-15 mg/day. A total of 8 patients were treated with 0.6256 mg Premarin daily for 25 days and 5 mg/day of medroxyprogesterone on days 15-25 (ERT, group 2); 7 were followed without ERT (group 1). A group of 17 women, matched for age, were randomly selected from our computerized data base to serve as a control group (group 3), and 10 women of similar age who were taking ERT only (group 4) were selected to compare the response to ERT to that of group 2. Bone density (BD) was measured in the lumbar spine baseline and at 1 year using dual-photon or dual-energy x-ray absorptiometry. Spine density did not change significantly during the year of observation in group 1. Although BD decreased in 5 of 7 patients, the change was not significant (-0.034 +/- 0.018 g/cm2, p = 0.10). In group 2 BD increased significantly, with 7 of 8 patients showing an increase (0.037 +/- 0.011 g/cm2, p = 0.008). BD did not change significantly in the control group (0.013 +/- 0.008 g/cm2, p = 0.16). Loss of bone from the spine was significantly greater in group 1 than in controls (p = 0.02), but changes in group 2 were similar to those in the control group (p = 0.66).(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of dorsal root entry zone lesion on spinal cord potentials evoked by segmental, ascending and descending volleys. The spinal cord potentials (SCPs) were recorded from the dorsal root entry zone (DREZ) and posterior epidural space in patients before and after dorsal root entry zone lesion (DREZL) during general anaesthesia. The SCPs from the DREZ activated by segmental, ascending and descending volleys were basically the same in fundamental waveform as those recorded from the posterior epidural space. Segmentally activated slow negative (N1) wave, reflecting synchronized activities of dorsal horn neurones, and positive (P2) wave, thought to indicate primary afferent depolarization, were affected by DREZL in all 4 subjects tested, even by contralateral stimulation, suggesting that these components of the segmental SCPs in man partly reflect the activities of the contralateral dorsal horn. The spike-like potentials activated by ascending volleys were not affected by DREZL, while the subsequent slow components were decreased in the lesioned level. This may indicate that ascending spinal cord tracts are not affected by the operation, and suggests that the origin of the slow components by ascending volleys lies at least in part in the segmental dorsal horn. The slow negative and positive components, recorded at a remote segment from DREZL, in response to the descending volleys, were augmented after DREZL, suggesting that activation of ascending or descending inhibition through a feedback loop via the supraspinal structures might occur at least transiently following DREZL. All components of the SCPs activated by descending volleys were decreased or disappeared in recording from the lesioned level, as expected. Thus, intra-operative recording of the SCPs during DREZL might be beneficial for monitoring and studying human spinal cord function.


Interferon treatment reduced adherence, invasiveness and intracellular multiplication of Shigella flexneri in coxsackie B1 virus-infected cells. The effect of interferon treatment on interaction of Shigella flexneri with in vitro cultured cells was investigated. Pretreatment of HEp-2 cells with human interferons had no effect on the susceptibility of cells to S. flexneri, measured by invasiveness and adhesiveness. Human leukocyte interferon and human recombinant interferon-alpha-A reduced adhesiveness, intracellular multiplication and invasiveness of S. flexneri in HEp-2 cells preinfected with coxsackie B1 virus. Also non-receptor mediated-phagocytosis was reduced by interferon treatment in virus infected cells. The interferon effects were dependent on continuous protein synthesis, because they were not expressed when cycloheximide or abrin was added to the virus infected cell cultures. No effect of interferon was detected on intracellular content of Na+ or K+, Na(+)-K+ activated ATPase activity or cytoplasma membrane polarity, in virus infected or control cell cultures. The interferon effect on bacterial invasiveness seems to be dependent on an interferon receptor interaction on cytoplasma membrane level because directly microinjected interferon showed no effect.


Ergotamine: its use in the treatment of migraine and its complications. This paper gives a review of the use of ergotamine in the treatment of migraine and discusses its side effects and the treatment of possible complications. It is concluded that ergotamine is an effective and valuable substance in the treatment of acute attacks of migraine. However, ergotamine remains a potentially dangerous substance, its possible side effects being multiple and in some cases very serious. In view of the important adverse effects, the further study of other molecules effective in the treatment of acute migraine attacks is warranted.


Stimulation of host-defense mechanism with synthetic adjuvants and recombinant cytokines against viral infection in mice. The efficacy of synthetic immunoadjuvants and recombinant cytokines for the potentiation of host-resistance against virus infection was investigated using mouse models infected with Sendai virus and herpes simplex type 1 virus (HSV). The synthetic MDP derivative, MDP-Lys(L18), and recombinant cytokines, IL-1 beta, IFN-gamma, G-CSF and GM-CSF were shown to be effective for the stimulation of nonspecific protection against Sendai virus infection in mice. Both MDP-Lys(L18) and GM-CSF were effective for the protection against HSV infection in cyclophosphamide (CY)-treated mice. B30-MDP was suggested to be useful as an immunoadjuvant for the potentiation of antigenicity of recombinant or component vaccines.


ADF (adult T cell leukemia-derived factor)/human thioredoxin and viral infection: possible new therapeutic approach. ADF (adult T-cell leukemia-derived factor), originally defined as an inducer of interleukin 2 receptor/alpha (IL-2R/alpha), is a homologue of thioredoxin. ADF is constitutively produced by human lymphoid cell lines transformed by human T-lymphotropic virus type I (HTLV-I) or Epstein-Barr virus (EBV). ADF augments the proliferation of HTLV-I and EBV transformed cells as an autocrine growth factor. These data are indicative of the possible involvement of ADF in virus-related transformation of cells and their autocrine growth. On the other hand, thioredoxin contains a redox active disulfide and has a reducing activity in the presence of thioredoxin reductase and NADPH. To clarify the role of ADF/thioredoxin system in the viral transformation, we tested the effect of 13-cis-retinoic acid (RA), which is a competitive inhibitor of thioredoxin reductase, on the growth of ADF high producing cells. The expression of IL-2R/alpha on HTLV-I (+) cells was suppressed by RA. RA dose-dependently reduced the cell number and viability of ADF high producing lymphoid cells. Moreover, it had a suppressive effect on the proliferation of ADF high producing cells. It is suggested that RA has an inhibitory effect on the activation and the growth of cells producing ADF and that inhibition of the ADF/thioredoxin system may be a new therapeutic approach for retrovirus-related disorders.


Differential regulation of human eosinophil, macrophage, and neutrophil functions by the allergic mediator release inhibitor CI-959. The cell activation inhibitor CI-959 [5-methoxy-3-(1-methyl-ethoxy)-N-1H- tetrazol-5-ylbenzo[b]thiophene-2-carboxamide, monosodium salt] was evaluated for its effect on the activation of human eosinophils, macrophages, and neutrophils by the phagocytic stimulus serum-opsonized zymosan (SOZ). CI-959 inhibited the respiratory burst of eosinophils and neutrophils, measured as the generation of superoxide anion, with IC50s of 9.6 and 14.5 microM, respectively. In contrast, 100 microM CI-959 inhibited superoxide anion generation by human macrophages by only 22.7%. The compound exhibited a different inhibition profile for lysosomal enzyme release from these cells. At 100 microM, CI-959 inhibited the release of eosinophil peroxidase and macrophage N-acetyl-beta-D-glucosaminidase by only 19.5 and 25.6%, respectively. In contrast, CI-959 inhibited the release of the neutrophil primary granule enzyme myeloperoxidase with an IC50 of 7.5 microM, while inhibiting release of lysozyme from secondary granules by only 11.4% at 100 microM. These results demonstrate that oxygen radical generation and lysosomal enzyme release by human leukocyte populations are differentially regulated by CI-959.


Biochemical mechanisms of hydrogen peroxide- and hypochlorous acid-mediated inhibition of human mononuclear leukocyte functions in vitro: protection and reversal by anti-oxidants. Both H2O2 (IC50 = 70 microM) and HOCl (IC50 = 8.5 microM) inhibited mitogen-induced MNL proliferation in a dose-dependent manner. This was found to be due to a depletion of intracellular ATP by at least two distinct mechanisms. HOCl and high concentrations (greater than 100 microM) of H2O2 inhibit ATP generation via sulfhydryl group oxidation on the active site of the glyceraldehyde-3-phosphate dehydrogenase (G3PDH) enzyme of the glycolytic pathway. On the other hand, low H2O2 concentrations cause ATP depletion by an activation of the DNA repair enzyme, poly(ADP-ribose)polymerase (pADPRP), leading to consumption of NAD+, an essential cofactor for G3PDH. The anti-oxidants ascorbate and cysteine protected MNL against the anti-proliferative effects of HOCl. Similar results were achieved with the HOCl-mediated inhibition of ATP production and G3PDH activity. However, ascorbate was unable to protect against H2O2-mediated inhibition of MNL functions, while cysteine protected against the inhibitory effects on ATP production and G3PDH activity, induced by this oxidant.


[Should one search for papillomavirus lesions in the male sex partner? Value of peniscopy. Literature review and personal experience]. Human papillomavirus (HPV) infection is closely related to genital carcinoma, especially cervical cancer in woman. Screening and treatment of male partner seems to be of particularly great interest for him self and also for preventing recurrence in female. A review of literature and a personal 70 patients series give highlight on peniscopy, poor results of local therapies and the need of a long term screening in the male partner.


[Comparative study of risk criteria for germ cell tumor]. The development of cisplatin-based chemotherapy has achieved a high cure rate in patients with advanced germ cell tumors (GCT) and it is more important to predict the prognosis of each patient before treatment and select the most suitable regimen of therapy. To date, 4 risk criteria for GCT are presented. From November, 1985 to April, 1991 our treatment protocol for GCT consisted of VAB-6 (vinblastine, actinomycin D, bleomycin, cisplatinum) or PVeBV (vinblastine, etoposide, bleomycin, high-dose cisplatin) as the induction chemotherapy and VIP (etoposide, ifosfamide, cisplatin) as the salvage chemotherapy. In total, 12 patients were entered on this protocol. They were divided into 2 groups based on the actual clinical course. Those who achieved complete remission within 3 cycles of chemotherapy were divided into "good response group" and others were into "poor response group". These results were compared with those classified by the 4 risk criteria. As a result of our study "The Indiana Staging System" seemed to be the most useful.


[Pedunculated hepatocellular carcinoma suspected of right adrenal tumor: a case report]. We report a rare case of extrahepatic growing hepatocellular carcinoma which was clinically diagnosed as right adrenal tumor. A 61-year-old woman was admitted for further examination of right flank pain and hypertension. Abdominal computed tomographic scan and echogram revealed a suprarenal mass. Hypercatecholaminemia was suspected from urinary analysis. Preoperative diagnosis was right adrenal tumor; suspected pheochromocytoma. On operation, we found the tumor was pedunculated from right lobe of liver and compressing normal right adrenal gland. Its clinical diagnosis was hepatocellular carcinoma. Ten months after operation she is still alive. We discuss the difficulty of differential diagnosis between extrahepatic growing hepatocellular carcinoma and adrenal tumor.


[Anti-bacterial zeolite balloon catheter and its potential for urinary tract infection control]. We present here a production of anti-bacterial zeolite balloon catheter and investigated its potential for controlling urinary tract infection. This anti-bacterial balloon catheter showed a bactericidal effect against Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli in vitro studies. The antibacterial effects were correlated with the concentration of anti-bacterial zeolite and size of catheter. We tried this catheter for 11 various urological patients who needed a long-term indwelling of a balloon catheter for lower urinary tract obstruction and neurogenic bladder. All patients were already indwelled silicon balloon catheter for 3 to 6 months and suffered with complicated urinary tract infection. Nine patients who had this anti-bacterial zeolite balloon catheter indwelled for 3 to 7 months and exchanged every 2 to 4 weeks, and no patient was taking antibiotics during this trial. Two patients (22.2%) showed good results by the urinary tract infection (UTI) criteria and 5 patients (55.4%) showed good effects by doctor's judgment. This anti-bacterial zeolite balloon catheter might be useful for patients who need long-term balloon catheter indwelling.


[A case of pre-Cushing's syndrome].

[A case of pre-Cushing's syndrome]. A 66-year-old female was admitted to Chiba University Hospital for the evaluation of a left adrenal mass which was incidentally discovered by computerized tomography. The patient had no clinical signs of Cushing's syndrome. Although the plasma ACTH level was suppressed, serum cortisol and urinary 17-OHCS levels were normal. Serum cortisol was not suppressed by dexamethasone and loss of diurnal rhythm of cortisol was observed. Uptake of 131I-aldosterone in the left adrenal gland was noted, but no accumulation was observed in the right one. Left adrenalectomy was performed. The tumor resected was 20 x 22 x 26 mm in size. Pathological diagnosis was adreno-cortical adenoma. Whether slight abnormality of adrenocortical function without clinical symptoms observed in the present case would develop into a clinically typical Cushing's syndrome remains to be solved.


Gastric and duodenal obstruction in patients with cholangiocarcinoma in the porta hepatis: increased prevalence after radiation therapy. Our objective was to study the imaging findings in patients who had gastric and duodenal obstruction as a long-term complication of cholangiocarcinoma and to determine if the obstruction was associated with radiation therapy. Between 1973 and 1989, 96 patients had either curative resection or palliative stenting for cholangiocarcinoma involving the hepatic duct bifurcation. Sixty-three (66%) also received adjuvant radiation therapy ranging from 4960 to 7220 rad (cGy). Gastric outlet or duodenal obstruction or both developed subsequently in seven of the 63 patients treated with radiation therapy. Radiographic studies, including upper gastrointestinal series and CT, and medical and surgical records for these seven patients were retrospectively reviewed. Upper gastrointestinal series in the seven patients with obstruction showed narrowing of the lumen, deformity and enlargement of gastric and duodenal mucosal folds, and delayed gastric emptying. CT performed in five of the seven patients showed thickening of the wall of the gastric antrum and small bowel and retained food and fluid within the stomach. All seven patients required gastrojejunostomy; at surgery, dense adhesions and fibrosis were found, and it was not evident whether the obstruction was due to the tumor or to radiation fibrosis. However, because this complication was seen only after radiotherapy, it was presumed to be radiation fibrosis. Our experience suggests that radiation therapy increases the risk of postoperative gastric and duodenal obstruction in patients undergoing surgery for cholangiocarcinoma.


The distinction between benign and malignant liver tumors on sonography: value of a hypoechoic halo. The purpose of this study was to determine the diagnostic value of the sonographic halo sign (defined as any hypoechoic rim in the periphery of a lesion) in distinguishing between benign and malignant isoechoic and hyperechoic liver lesions on sonography. Sonograms of the liver in 50 patients with proved benign liver tumors and in 50 patients with proved malignant liver tumors (seven primary liver neoplasms, 43 metastases) selected during a 13-month period were retrospectively analyzed by four radiologists who had no knowledge of the patients' clinical findings or the final diagnoses. Only a single sonogram was studied in each case. The presence or absence of a hypoechoic halo on the sonogram was the only criterion for distinguishing malignant from benign hepatic lesions. For 95 of 100 hepatic lesions, the four radiologists were almost (three vs one) or completely (four vs zero) in agreement about the presence or absence of a hypoechoic halo. In the five cases where there were conflicting decisions (two vs two), a final decision (four vs zero) was achieved by reviewing the entire series of sonographic images. A halo could be detected in 44 malignant tumors (88%) and in only seven benign tumors (14%) (sensitivity, 88%; specificity, 86%; positive and negative predictive values, 86% and 88%, respectively). The sonographic halo sign was particularly helpful in distinguishing hemangiomas (n = 29) from metastases (n = 43) (positive and negative predictive values, 95% and 87%, respectively). The results of this study suggest that the halo sign on sonograms is useful to distinguish benign from malignant isoechoic or hyperechoic tumors.


Pathologic explanation for hypoechoic halo seen on sonograms of malignant liver tumors: an in vitro correlative study. The purpose of this study was to evaluate the morphologic substrate of the hypoechoic halo seen on sonograms of malignant liver tumors. We used sonograms and pathologic examinations to evaluate 17 cadaveric livers with macroscopic tumors (three primary liver tumors, 14 metastases). During sonography (3.5 and 5.0 MHz), a representative section plane was marked, and the same section was examined histologically. Emphasis was placed on the architecture of the tumor and the morphology of the periphery of the tumor that could account for the hypoechoic halo seen on sonograms. In 13 of 17 hepatic tumors, a hypoechoic halo was detected on sonograms. Histopathologic examination showed an intratumoral rim consisting of proliferating tumor cells in 12 cases and an extratumoral rim of compressed liver parenchyma in all 13 cases. A detailed comparison of sonographic and histopathologic findings showed that the hypoechoic halo corresponded to a greater concentration of tumor cells and areas of less marked fibrosis and necrosis in the periphery of the tumors. This occurred in 11 cases. In one case, histologic studies showed that the hypoechoic rim was caused by compressed liver parenchyma. In another case, the hypoechoic halo was caused by intratumoral (cellular peripheral zone of tumor) and extratumoral (compressed liver parenchyma) components. All four tumors without a halo at sonography were uniform histologically. The sonographic halo seen on sonograms of malignant liver tumors seems to be caused predominantly by a zone of proliferating tumor in the periphery of the lesion.


Carbon tetrachloride toxicity. Agency for Toxic Substances and Disease Registry. Industrial carbon tetrachloride is used in the synthesis of chlorofluorocarbons and chlorinated solvents. Although both production and use of carbon tetrachloride are declining, industrial and hazardous waste sites remain as sources of exposure. Workers using carbon tetrachloride or products that contain it are at highest risk of exposure. Diabetics and persons who drink alcohol may have an increased risk of adverse effects following exposure to carbon tetrachloride. Acute exposure may result in rapid central nervous system depression. Symptoms of hepatic and renal toxicity may arise one to four days later. Carbon tetrachloride is considered a possible carcinogenic agent. Administration of N-acetylcysteine may reduce complications of severe carbon tetrachloride exposure. Removal of the source of exposure and avoidance of other hepatotoxicants is the only treatment for chronic carbon tetrachloride toxicity.


Percutaneous angioplasty for renovascular hypertension due to fibromuscular dysplasia. Because the cause of hypertension is reversible in only 5 percent of patients, extensive initial work-up should only be considered in selected cases. Secondary causes should be suspected in patients whose hypertension begins before age 30 or after age 50 and in patients whose hypertension suddenly worsens after a long period of good control, becomes severe or malignant, or remains refractory to maximal medical therapy. A sudden reduction in renal function in a hypertensive patient and the discovery of a unilateral small kidney may also raise suspicion of a secondary cause. Renovascular disease, one of the most common secondary causes of hypertension, is usually the result of atherosclerosis in older patients and the result of fibromuscular dysplasia in younger patients. Physical examination seldom contributes to the diagnosis. The classic upper abdominal or flank bruit occurs in only 30 to 50 percent of patients with renovascular disease, and is not uncommon in patients with essential hypertension. The gold standard for diagnosis of renovascular disease remains the arteriogram. Transluminal renal angioplasty may be performed during arteriography if a high-grade stenosis is identified. Other management options include medical therapy and surgical revascularization with grafts.


Synovial sarcomas of the head and neck: CT and MR findings. The authors present three cases of histologically proved synovial sarcoma. CT is useful in assessing erosive or destructive changes in bone, and in demonstrating calcifications. MR characteristics are nonspecific; calcifications within these tumors can be missed on MR. MR can help to assess tumor extension, vascular invasion, and hemorrhage within the tumor.


Differences in structure of angiotensin-converting enzyme inhibitors might predict differences in action. Angiotensin-converting enzyme (ACE) inhibitors probably work by inhibition of tissue-located ACE, and they differ with regard to their relative ability to inhibit ACE in different organs. This apparent tissue selectivity may stem from either differences in tissue bioavailability or from a different affinity for the enzyme. The affinity of the ACE inhibitor for a particular enzyme is not only determined by the structure of the inhibitor, but also by the structure of the enzyme. ACE enzymes from different tissues may be slightly different, and this may have some bearing on the relative affinities of different ACE inhibitors for ACE from different tissues. The duration of inhibition in a particular tissue reflects not only the affinity of that inhibitor for the tissue enzyme, but also reflects the ease or difficulty with which the active ACE inhibitor is released from that tissue. Whether the beneficial effects of ACE inhibitors on experimentally induced myocardial infarction and reperfusion arrhythmias are due to the presence of a sulfhydryl group or are mainly related to the ACE inhibitor-mediated bradykinin potentiation remains a matter of controversy.


Drug-patient interactions and their relevance in the treatment of heart failure. The effects of congestive heart failure (CHF) on drug disposition and elimination are many and varied. Indeed, the pharmacokinetics of many of the drugs used to treat CHF are significantly altered by the patient's underlying condition. Reduced gastric emptying in CHF delays absorption and decreases the peak plasma concentrations of furosemide, bumetanide, and digoxin. Moreover, drugs that have a high hepatic extraction ratio (organic nitrates, morphine, prazosin, and hydralazine) achieve higher than expected plasma concentrations in patients with CHF. In contrast, drugs requiring biotransformation to active forms, e.g., angiotensin-converting enzyme (ACE) inhibitors such as enalapril, perindopril, quinapril, and ramipril, generally have lower than expected plasma concentrations. Nevertheless, ACE inhibitors can impair renal function in CHF, leading to an actual increase in plasma concentrations. However, decreases in absorption and first-pass metabolism are often offset by reduced hepatic and renal clearance. The overall absorption of lisinopril may be reduced in some CHF patients; consequently, the onset of effect is delayed but is often more prolonged.


Angiotensin-converting enzyme inhibition, the sympathetic nervous system, and congestive heart failure. The Australian Zestril (Lisinopril) Study Group. Catecholamines have been found to be powerful indicators of prognosis in patients with congestive heart failure. However, it is uncertain whether catecholamines are a marker for decreased cardiac performance or part of the pathologic process. Catecholamines, exogenously derived beta-adrenergic stimulants, and drugs that amplify sympathetic responsiveness produce early hemodynamic benefits, but do not appear to provide long-term improvement in terms of symptoms or exercise tolerance, whereas blockade of the beta-adrenoceptor appears to have little early benefit but may improve long-term prognosis. This suggests that in the long term, increased catecholamine levels may be deleterious. Angiotensin-converting enzyme (ACE) inhibitors can modulate circulating catecholamines, and the persistence and degree of ACE inhibition may be important not only in reducing catecholamines, but possibly also in reducing mortality in heart failure. It appears that ACE inhibitors definitely reduce mortality in congestive heart failure. It remains to be documented whether the persistence and degree of ACE inhibition is a factor in this effect, and, thus, comparison of short- with long-acting ACE inhibitors and study of the dosage of ACE inhibitors are of importance. The extent to which modulation of the sympathetic nervous system by ACE inhibitors is an important mechanism in their effect in reducing mortality remains to be established.


Angiotensin-converting enzyme inhibitors and renal function in heart failure. Patients with severe heart failure often exhibit signs of an impaired renal function. As judged from serum urea and creatinine concentrations, renal function may deteriorate further after the addition of angiotensin-converting enzyme (ACE) inhibitors to therapy. The beneficial effect of unloading the failing heart by reducing the systemic outflow resistance is opposed by a potentially harmful effect of unloading the kidney by preferentially reducing the outflow resistance of the glomerulus. However, development of functional renal insufficiency is unlikely and is a rare cause for withdrawing ACE inhibitors when certain precautions are considered: (1) The initial dose of the ACE inhibitor has to be reduced with increasing severity of heart failure (the titration period thereafter should be monitored carefully); (2) an increase in serum creatinine not exceeding 30% of the basal value may be taken as evidence for a beneficial action of the drug, which in addition to altering cardiac function alters kidney function (when the increase in serum creatinine is considered to be of clinical significance, it seems wise to reduce the dose of diuretics first--thereby neuroendocrine stimulation can be attenuated and the dependency of renal filtration from angiotensin II-induced efferent vasoconstriction can be reduced); and (3) the coadministration of inhibitors of prostaglandin synthesis (e.g., acetylsalicylic acid) appears to be associated with a higher risk of impairing renal function: the decrease in glomerular filtration rate is more marked and the compensatory increase in renal plasma flow following ACE inhibition is no longer observed.


Angiotensin-converting enzyme inhibitors, left ventricular dysfunction, and early heart failure. A study was undertaken to examine the effects of the angiotensin-converting enzyme inhibitor lisinopril on exercise performance in 18 patients with major impairment of left ventricular systolic function. The study was a randomized, double-blind, crossover design, and patients received treatment with either once-daily lisinopril (2.5-10 mg) or placebo for a period of 6 weeks. A total of 15 patients completed the study. Compared with placebo, lisinopril had no significant effect on supine or standing blood pressure or heart rate. Although lisinopril had no effect on exercise duration during a low-intensity exercise protocol, in patients undergoing a high-intensity exercise protocol, there was a trend toward improved exercise time and peak oxygen consumption improved significantly. In addition, treatment with lisinopril resulted in an increase in renal blood flow and a reduction in glomerular filtration rate. Moreover, administration of once-daily lisinopril 10 mg resulted in a decrease in plasma concentrations of angiotensin II, aldosterone, and atrial natriuretic peptide, and an increase in plasma concentrations of active renin.


GISSI-3 study protocol on the effects of lisinopril, of nitrates, and of their association in patients with acute myocardial infarction. The role of thrombolysis in the acute phase of myocardial infarction (AMI) has been definitely established in terms of mortality and ventricular function, as has the equivalence of different thrombolytic agents. The Second Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI-2) trial showed that a large number of patients have either clinical heart failure or severe left ventricular damage on discharge from the hospital, with a large risk of death and poor prospects in terms of quality of life. Additional measures to limit ventricular damage are therefore essential to reducing morbidity. The GISSI-3 study protocol on the effects of lisinopril and nitrates, used alone or in combination, in patients with AMI is described in detail.


Long-acting angiotensin-converting enzyme inhibition: once-daily lisinopril versus twice-daily captopril in mild-to-moderate heart failure. Once-daily lisinopril (5-20 mg) was compared with twice-daily captopril (12.5-50 mg) in a double-blind, randomized, parallel-group study of angiotensin-converting enzyme (ACE) inhibition conducted in 31 centers for 12 weeks in patients with heart failure (New York Heart Association class II-III) who were currently receiving digitalis and/or diuretics. The drugs were compared with regard to their effects on exercise duration, measured with bicycle ergometry, and on ectopic activity, measured using Holter monitoring. Both drugs significantly increased exercise duration after both 6 and 12 weeks of randomized treatment. Neither ACE inhibitor had any significant impact on the hourly rate of either ventricular ectopic counts or couplets, nor was there any difference between treatments with regard to the proportions of patients in whom ventricular ectopic counts were reduced. Both drugs were well tolerated, with no differences observed between treatments. Potassium, urea, and creatinine levels remained stable for both treatments throughout the study.


Comparison of treatment with lisinopril versus enalapril for congestive heart failure. The effect of lisinopril 5-20 mg once daily or enalapril 5-20 mg once daily on exercise capacity, ventricular ectopic activity, and signs and symptoms of heart failure have been studied in 278 patients with mild-to-moderate (New York Heart Association [NYHA] classes II and III) heart failure in a randomized, double-blind, parallel-group study of 12 weeks' duration. Exercise duration was significantly increased by both angiotensin-converting enzyme (ACE) inhibitors after 6 and 12 weeks of treatment compared with their respective baseline values. There was a trend toward a greater increase in exercise duration on lisinopril after 12 weeks, although this did not reach statistical significance (p = 0.0748). There were no significant treatment differences with respect to the effect of the 2 drugs on ventricular ectopic counts, couplets, or nonsustained ventricular tachycardia. Both drugs were equally effective in improving NYHA grading and symptoms. Neither treatment had any significant effect on mean heart rate or mean blood pressures. Both treatments were equally well tolerated. The most commonly reported adverse events on both drugs were cough, dizziness, fall in blood pressure, vertigo, and myocardial infarction. The results of this study indicate that lisinopril 5-20 mg once daily is at least as effective and well tolerated as enalapril 5-20 mg once daily.


Comparison of lisinopril versus digoxin for congestive heart failure during maintenance diuretic therapy. The Lisinopril-Digoxin Study Group. Lisinopril 5-20 mg once daily was compared with digoxin 0.125-0.375 mg once daily in a double-blind, randomized, parallel-group study involving 217 patients with mild-to-moderate heart failure (New York Heart Association [NYHA] grades II-III) who were maintained on optimized diuretic therapy. After 6 weeks of treatment, digoxin and lisinopril had increased exercise duration by 18 seconds (p = 0.015) and 32 seconds (p = 0.0007), respectively, versus the baseline run-in period. The difference between treatments was not statistically significant (p = 0.1343). After 12 weeks, digoxin and lisinopril had increased exercise duration by 29 seconds and 51 seconds, respectively. The effect of digoxin compared with the baseline value was not significant but that for lisinopril was (p = 0.0027). The difference between treatments approached statistical significance (p = 0.0813). There was no difference between lisinopril and digoxin with regard to their effects on the frequency of ventricular ectopic counts, couplets, or nonsustained ventricular tachycardia. Blood pressures were not significantly different between treatments, although both systolic and diastolic blood pressure were consistently lower in the lisinopril group throughout randomized treatment. The proportions of patients demonstrating an improvement in NYHA grading were similar for both lisinopril and digoxin. Both treatments had similar effects on the symptoms of heart failure. Both drugs appeared to be equally well tolerated with a similar frequency of adverse events reported for both drugs (30% for lisinopril vs 29% for digoxin). Withdrawals from treatment were of a similar frequency for both treatments.(ABSTRACT TRUNCATED AT 250 WORDS)


Safety of long-term use of lisinopril for congestive heart failure. Early clinical experience with lisinopril suggested that it was well tolerated in congestive heart failure (CHF). An analysis of data from greater than 1,000 patients treated with lisinopril has been performed to examine the long-term safety of lisinopril in CHF. Of these, 620 have been studied for up to nearly 4 years, and a further 440 have been studied in comparative trials for 3 months. When patients who received lisinopril or placebo for the same period were compared, the proportion of lisinopril patients reporting an adverse event was 44.1% compared with 39.4% on placebo. Over a 4-year period, 205 patients (33.1%) discontinued treatment. About 33% of these died, 33% withdrew due to clinical adverse events, 21 (3.4%) were withdrawn because of adverse laboratory findings, and 56 (9.0%) withdrew for reasons unrelated to treatment. Sixteen patients (2.6%) withdrew because lisinopril was deemed ineffective. The most frequently reported drug-related adverse laboratory findings were increases in blood urea nitrogen, blood urea, serum creatinine, and plasma potassium. There appeared to be no differences in the pattern of adverse events with respect to the race of the patient. Elderly patients and those with the most severe forms of heart failure appeared to be at greater risk for an adverse event. Evaluation of the safety of lisinopril compared with enalapril, captopril, and digoxin in controlled clinical trials shows all the angiotensin-converting enzyme inhibitors to be equally well tolerated with a closely similar range of adverse events, suggesting that the satisfactory safety profile of lisinopril is shared by other drugs of this class.(ABSTRACT TRUNCATED AT 250 WORDS)


Importance of long-acting angiotensin-converting enzyme inhibitors for congestive heart failure. The renin-angiotensin system (RAS) has both localized and systemic effects in the pathophysiology of heart failure. These may lead to structural changes in the heart and blood vessels as well as to more disseminated symptomatology, including vasoconstriction and both salt and water retention. In association with other neurohormonal mechanisms, such as the sympathetic nervous system, these latter effects result in an elevated work load for the heart. The increase in neurohormonal activity, seen in some patients with heart failure, may result in a loss of circadian variation in heart rate and blood pressure and deprive the heart of a needed reduction in work load during the night. The suppression of such neurohormonal activity through the use of long-acting angiotensin-converting enzyme (ACE) inhibitors, such as lisinopril, provides a means of controlling such symptoms. In comparison with short-acting ACE inhibitors, such long-acting suppression of the RAS may have a number of advantages. These include a more sustained increase in exercise duration, improvement in left ventricular ejection fraction, and, speculatively, a better influence on patient mortality.


Prospective, randomized, controlled comparison of the effects of low-fat and low-fat plus high-fiber diets on serum lipid concentrations. Previous studies examining the hypocholesterolemic effects of high-soluble-fiber diets have not been designed to control for dietary fat intake. Serum cholesterol reductions may therefore be accounted for by differences in consumption of fat. Moderately hypercholesterolemic, nonobese, Caucasian men and women, 30-50 y old were randomly assigned to low-fat, low-fat plus high-fiber, or usual-diet groups and followed for 12 mo. At 12 mo the high-fiber group consumed significantly more soluble fiber than both the low-fat and usual-diet groups (P = 0.0063 and P = 0.0001); the high-fiber group did not differ from the low-fat group in quantity of dietary fat consumed. The high-fiber group experienced a greater average reduction (13%) in serum cholesterol than did the low-fat (9%) and usual-diet (7%) groups. After adjustment for relevant covariates, the reduction in the high-fiber group was significantly greater than that in the low-fat group (P = 0.0482). Supplementation with soluble fiber reduces serum cholesterol beyond the reduction observed with low-fat diet alone.


Effects of age and sex on copper absorption, biological half-life, and status in humans. Healthy, free-living men and women aged 20-83 y (n = 127) were studied to determine the effects of age and sex on copper absorption, biological half-life (BH), and status. Copper absorption was greater in women (71%) than in men (64%) aged 20-59 y (P = 0.02), but did not differ in men and women aged 60-83 y. BH of 67Cu ranged from 13 to 33 d and differed between men and women aged 20-59 y (P = 0.006), but not between men and women aged 60-83 y. Plasma copper, enzymatic ceruloplasmin (Cp), and immunoreactive (RID) Cp were significantly higher in women than in men (P < 0.005), but superoxide dismutase (SOD) and in vitro 67Cu uptake by red blood cells did not differ. Plasma copper, RID Cp, and cytochrome oxidase in platelets and mononuclear cells were significantly affected by age (P < 0.005). Oral contraceptives elevated plasma copper, enzymatic Cp, and SOD activity but not copper absorption and BH in women aged 20-39 y. Copper intake from self-selected diets was 0.9-1.2 mg/d for women and 1.2-1.3 mg/d for men, but net copper absorption (micrograms Cu.kg body wt-1.d-1) did not differ. Thus, dietary copper intake requirements may differ between men and women.


Effect of intravenously infused eicosapentaenoic acid on the leukotriene generation in patients with active Crohn's disease. Ten patients with active Crohn's disease who have been managed with parenteral-nutrition therapy were administered a lipid emulsion either with [containing 0.6 g eicosapentaenoic acid (EPA)] or without fish oil for 2 wk. We isolated polymorphonuclear leukocytes (PMNLs) from the patients before and after this treatment and measured the amounts of leukotriene B4 (LTB4) and leukotriene B5 (LTB5) generated by activated PMNLs by reversed-phase HPLC. The LTB5 generation in active Crohn's disease before this treatment was significantly lower than in healthy control subjects. The amount of LTB5 and the LTB5-LTB4 ratio increased significantly after fish-oil supplementation. The difference with LTB4 was not statistically significant. We have shown that daily intravenous administration of 0.6 g EPA influenced the generation of leukotrienes in active Crohn's disease even after short-term treatment. Further investigations are necessary to clarify the correlation between EPA and clinical improvement in Crohn's disease.


Hepatitis C virus in peripheral blood mononuclear cells. RNA extracted from plasma and peripheral blood mononuclear cells of patients with chronic hepatitis C were used as the template for reverse transcription followed by double in vitro enzymatic amplification with nested primers. Hepatitis C virus was detected in 14 of 15 (93.3%) plasma specimens and in 8 of 15 (53.3%) peripheral blood mononuclear cell specimens obtained from patients with chronic hepatitis C and abnormal liver functions. The results suggest that hepatitis C virus could be found frequently in peripheral blood mononuclear cells of patients with chronic hepatitis C. Whether the presence of hepatitis C virus in peripheral blood mononuclear cells plays any role in the pathogenesis of diseases associated with hepatitis C virus infection remains to be determined.


Small B-cell lymphoid neoplasms with coexisting T-cell lymphomas. The simultaneous occurrence of a small B-cell lymphocytic neoplasm and a T-cell lymphoma in the same lymph node biopsy specimen is documented in two patients. The biopsy from the first patient, who had a 5-year history of chronic lymphocytic leukemia, showed evidence of a small B-cell lymphocytic neoplasm coexisting with a large-cell lymphoma of T-cell phenotype. The lymph node biopsy specimen from the second patient showed features of small lymphocytic lymphoma of B-cell phenotype, coexisting with a small-cell pleomorphic lymphoma of T-cell phenotype. The lymph node specimens from both patients met strict criteria for composite lymphomas. The clinical and morphologic findings in the first patient are those of "Richter's transformation" of chronic lymphocytic leukemia. The lymph node biopsy specimens from these two patients demonstrate that small B-cell lymphocytic neoplasms may coexist with T-cell lymphomas.


End-stage renal disease and primary hypogonadism associated with a 46,XX karyotype. To determine the cause of absent sexual development in a 17-year-old girl with end-stage renal disease. Case study. Seventeen-year-old girl with end-stage renal failure. None. The patient had phenotypically normal external female genitalia, müllerian duct hypoplasia, and no ovaries. Her serum gonadotropin levels were in the castrate range at baseline and after gonadotropin-releasing hormone stimulation. Her karyotype, in lymphocytes and cultured fibroblasts, was 46,XX. Analysis of genomic DNA, following polymerase chain reaction-amplication with oligonucleotide primers corresponding to the Y-encoded zinc finger protein ZFY and the testis-determining SRY gene, showed Y chromosome material in a male control but none in the patient. The results suggest a diagnosis of Frasier syndrome, a disorder characterized by true gonadal dysgenesis and end-stage renal disease occurring in normal phenotypic girls. Although previously reported only in individuals with a 46,XX karyotype, our studies indicate that Frasier syndrome may also occur in 46,XX girls. Delayed puberty is not uncommon in renal failure. This case illustrates the importance of measuring gonadotropin levels in teenage girls with delayed puberty and renal failure, particularly if the origin of the renal disease is obscure.


Variable presentation of cytochrome c oxidase deficiency. To describe three patients with cytochrome c oxidase deficiency. Patient series. Tertiary care children's hospital in Arkansas. A sibling pair and an unrelated patient referred for evaluation and found to have cytochrome c oxidase deficiency. None. Affected individuals had the characteristic presentation of psychomotor regression, growth deficiency, and lactic acidosis. The severity of the clinical course was found to correlate with the lactate-pyruvate ratio. Two of the infants had evidence, on magnetic resonance imaging, of subacute necrotizing encephalomyelopathy (Leigh disease). The most severely affected child had an unusual presentation of prenatal onset of structural anomalies including glabellar prominence, abnormal hair, loose skin, inguinal hernias, and hypospadias. The presentation and clinical course of cytochrome c oxidase deficiency are highly variable and the diagnosis of cytochrome c oxidase deficiency should be considered in all patients with lactic acidosis or subacute necrotizing encephalomyelopathy. Particular consideration should be given to this diagnosis when lactic acidosis is found in a neonate with structural anomalies.


The dysphoria of heroin addiction.

The dysphoria of heroin addiction. Levels of dysphoria and opioid dependence were assessed in 54 male patients with heroin addiction applying for drug treatment. During a period of naturalistic heroin use, symptom measures of dysphoria and of spontaneous opioid withdrawal reported by these patients were highly correlated. Upon admission to treatment, levels of dysphoria and opioid withdrawal were assessed before and after a pharmacological challenge with either 0.4 mg naloxone or placebo. Signs and symptoms of opioid withdrawal and symptoms of dysphoria increased in patients following naloxone, but not placebo administration. Naloxone-induced changes in symptoms of dysphoria were correlated with changes in opioid withdrawal as assessed by both subjective and objective measures. These findings suggest that dysphoric mood states in heroin addicts may be, in part, pharmacological sequelae of their drug dependence. Dysphoria due to opioid withdrawal may contribute to the initiation and maintenance of heroin use, and to the high rates of syndromal affective disorders reported in this population.


Ten-year follow-up after admission to methadone maintenance. To assess the long-term effects of methadone maintenance, we compared the 10-year outcomes of 95 chronic opioid users who spent at least one cumulative year on methadone with those of 77 chronic opioid users who spent less than one cumulative year on methadone. All subjects were men and 90% were Mexican-American. The two groups were similar on 12 of 15 background variables. During the 10-year period, the methadone group had a cumulative mean of 54 months on methadone, while the comparison group had a cumulative mean of only 2 months on methadone. On social performance, as measured by months employed and months institutionalized, the methadone group did significantly better than did the comparison group. On months of voluntary abstinence, however, the comparison group did significantly better than did the methadone group. The mean of the comparison group, 36 months, was three times greater than that, 12 months, of the methadone group. At the end of the 10-year period, 26% of the comparison group but only 7% of the methadone group had been in continuous voluntary abstinence for 3 years or longer. Methadone maintenance for 1 year or longer was inversely related to abstinence during and at the end of the 10 years. This finding seems consistent with the hypothesis that methadone maintenance for 1 year or longer impedes eventual recovery from opioid dependence. For many patients, however, the benefits of prolonged maintenance could outweigh the possible cost of diminished likelihood of eventual recovery.


Implementation issues and techniques in randomized trials of outpatient psychosocial treatments for drug abusers: recruitment of subjects. We reviewed nine randomized clinical trials of outpatient psychosocial treatments for drug abuse to ascertain implementation problems and solutions that the researchers developed. The most common problem was subject recruitment. Inadequate recruitment can disrupt a project's timetable, preoccupy its staff, reduce the trial's ability to detect treatment differences, and perhaps result in the trial's abandonment. The causes of recruitment problems include the need for large samples and multiple eligibility criteria, subject reluctance to be a "guinea pig," low client treatment motivation, client dislike of research procedures, clinicians' distrust of research, and difficulties collaborating with treatment agencies. Solutions include realistic assessment of the target population's size, use of mass media, statistical adjustments to minimize unnecessary sample exclusions, variable treatment assignment ratios, and prevention of common collaboration difficulties.


Esophageal and small bowel obstruction from guar gum-containing "diet pills": analysis of 26 cases reported to the Food and Drug Administration. Twenty-six domestic reports of suspected adverse reactions from the guar gum-containing diet pill, Cal-Ban 3000 (filed with the FDA) were reviewed. There were 18 instances of esophageal obstruction, seven instances of small bowel obstruction, and one individual who was reported to have died after ingestion of Cal-Ban 3000, but for whom insufficient details were provided to assess causation. There were 14 women and 11 men (mean age 46.3 yr; range 17 to 67 yr) for whom sufficient information was available. Preexisting esophageal or gastric disorders were present in 50% of those with esophageal obstruction, including peptic stricture, pyrosis, hiatal hernia, esophagitis, gastric stapling procedure, Schatzki ring, and muscular dystrophy. Fourteen of these 18 patients with esophageal obstruction were treated successfully by endoscopy, although the tenacious gel-like consistency of the material was often difficult to remove. Two patients required rigid esophagoscopy when flexible endoscopy was unsuccessful. This resulted in the death of one patient who developed a pulmonary embolism after surgical repair of an intraoperative esophageal tear. For the seven patients with small bowel obstruction, no specific predisposing factors were mentioned. One individual required exploratory laparotomy, and inspissated tablets were found in the ileum. These cases, spontaneously reported to the FDA, are very similar to those reported in the literature. The water-holding capacity and gel-forming tendency of guar gum permits it to swell in size 10- to 20-fold, and may lead to luminal obstruction, especially when an anatomic predisposition exists. Such products have been banned in Australia, and Cal-Ban 3000 has recently been removed from the market in the United States. However, unsuspecting patients who are still in possession of the product should be apprised of the potential complications that may arise with its use.


Interleukin-8 and neutrophil markers in colonic mucosa from patients with ulcerative colitis. In this study, mediators of inflammation were characterized in colonic and terminal ileum mucosa from subjects with ulcerative colitis. We considered the role of two different chemotactic factors (interleukin-8 and leukotriene B4) and of myeloperoxidase in the pathology of inflammatory bowel disease. Serial biopsy specimens were taken at different sites, washed in 0.02 M phosphate/saline buffer, homogenized, and then sonically disrupted. In both the proximal and distal regions of the colonic mucosa of ulcerative colitis patients, there was a more than 10-fold increase in interleukin-8 levels over that in control subjects (> 300 pg/mg protein vs. 30 pg/mg protein in controls, p < or = 0.01). However, terminal ileum levels of interleukin-8 were the same in ulcerative colitis and control groups (150 pg/mg protein). There was also a 3- to 5-fold increase in leukotriene B4 levels and a several-fold increase in myeloperoxidase levels throughout the colonic mucosa in patients with ulcerative colitis. This study demonstrates that 1) interleukin-8 may have an immunoregulatory role in the pathogenesis of inflammatory bowel disease, and 2) interleukin-8, myeloperoxidase, and leukotriene B4 may be useful markers for the biochemical identification of inflammatory bowel disease.


Combined transcatheter arterial embolization and expanded liver resection for hepatocellular carcinoma with multiple intrahepatic metastasis. After repeated transcatheter arterial embolization, a patient with hepatocellular carcinoma with multiple intrahepatic metastases in the entire lobe was successfully treated by extended right lobectomy with resection of the retrohepatic inferior vena cava under extracorporeal venovenous bypass.