Effects of feeding lactating dairy cows diets containing whole soybeans and tallow. Four multiparous Holstein cows averaging 133 d postpartum and fitted with ruminal cannulas were utilized in a 4 x 4 Latin square design to investigate the effects of feeding diets containing whole soybeans and tallow. Treatments were 1) control, no added fat; 2) control and 10% whole raw soybeans; 3) control, 10% whole raw soybeans, and 2.5% tallow; and 4) control, 10% whole raw soybeans, and 4.0% tallow. Cows were fed for ad libitum intake a diet of alfalfa haylage, corn silage, and concentrate (45:5:50, DM basis). Intakes of DM and production of milk, milk CP, milk SNF, and 4% FCM were not affected by feeding supplemental fat. Production of milk fat and weight percentages and yields of long-chain fatty acids in milk fat were increased, whereas weight percentages and yields of short- and medium-chain fatty acids were decreased by feeding supplemental fat. Digestibilities of DM, OM, energy, cellulose, and fatty acids were decreased slightly when fat was added to the diet, but utilization of energy and N for production of milk was not altered. Supplemental fats increased concentrations of NEFA and cholesterol in plasma. These data indicate that relatively large amounts of unprotected fat can be added to the diet of lactating dairy cows without deleterious effects on milk composition, ruminal fermentation, or nutrient digestibilities.


Lactational responses of dairy cows fed unsaturated dietary fat and receiving bovine somatotropin. Feeding unsaturated dietary fat to lactating dairy cows receiving bST may effectively alter the fatty acid composition of milk fat. This was tested using 16 Holstein cows assigned to one of four treatments during midlactation. Treatments were control, control diet with 15.5 mg of bST/d per cow, dietary fat from sunflower seeds and bST, or dietary fat from safflower seeds and bST. Diets were formulated to contain 19% CP and contained 25% corn silage, 25% alfalfa hay, and 50% concentrate mix on a DM basis. Milk yield was not significantly higher when bST was administered and increased with added fat diets (29.5, 32.7, 40.0, and 34.1 kg/d for the control, control with bST, sunflower seed with bST, and safflower seed with bST treatments, respectively). Percentage of milk fat was similar for all treatments. Concentrations of long-chain and unsaturated fatty acids in milk were increased slightly by bST and substantially with added fat. Milk protein percentages were not influenced by bST but were reduced by approximately .2 unit with added fat. Added unsaturated dietary fat coupled with bST increased milk yield and produced a greater concentration of unsaturated fatty acids in milk.


Responses of dairy cows to additions of distillers dried grains with solubles in alfalfa-based diets. Twenty-four Holstein cows in wk 3 through 12 of lactation were used to evaluate distillers dried grains with solubles as a protein source for alfalfa-based diets. Diets were formulated containing 0, 10.1, 20.8, or 31.5% distillers dried grains with solubles. Crude protein in these diets was 13.9, 16.0, 18.1, and 20.3%. Milk yield increased linearly with increasing dietary CP, whereas DMI was not affected. Dry matter intake averaged over 4% of BW for all treatments. Intake of undegraded intake protein was .93, 1.27, 1.63, and 1.97 kg/d. Yields of milk protein, casein, and lactose all increased linearly with increasing dietary CP. The proportion of milk N as whey N decreased, whereas N as NPN increased, with increasing dietary CP. Plasma urea N and essential and branched-chain AA increased linearly, and nonessential AA decreased linearly, with increasing dietary CP. Increasing the concentration of CP in the diet from 13.9 to 18.1% by the addition of distillers dried grains with solubles was beneficial to cows fed alfalfa-based diets in early lactation. Little additional benefit was observed by feeding greater than 18.1% dietary CP.


Disappearance of phosphorus in phytate from concentrates in vitro and from rations fed to lactating dairy cows. Objectives were to determine concentrations of P in phytate in selected concentrates, disappearance of P in phytate from these concentrates in vitro, and extent of hydrolysis of phytate in vivo. Total P and P in phytate were determined for eight concentrates; 32 to 81% of total P was in phytate. Six concentrates were incubated in vitro to determine the extent of phytate disappearance from solids and its appearance and disappearance from solution. Greater than 90% of P in phytate disappeared from solids between 6 and 8 h of incubation in vitro (wheat middlings, rice bran, hominy, soybean meal, and dried distillers grains) or between 12 and 24 h (cottonseed meal). Phosphorus in phytate in solution was hydrolyzed by 12 h except for cottonseed meal (by 24 h). Hydrolysis of the inositol ring to release P in vivo was greater than 99%, based on total fecal collection from 11 cows and the use of Cr as an indigestible marker in excreta, and between 94 to 98% for the same samples when acid detergent lignin was used as an indigestible marker to calculate phytate disappearance. These results further indicate that P in phytate should be considered available to lactating dairy cows when rations to meet their P requirements are being formulated.


Genetic parameters of conformation traits, milk yield, and herd life in Holsteins. Genetic parameters were estimated simultaneously for 5 herd-life traits, 15 conformation (type) traits, and milk yield measured in first lactation for 128,601 Holstein cows. Heritabilities of all traits were higher in registered than in grade cows. Genetic correlations of linear type traits with first lactation yield ranged from -.48 for udder depth to .54 for dairy form. Genetic correlations among milk yield and herd-life traits were all positive except for milk-corrected herd life in grade cows. Udder traits had largest absolute genetic correlations with herd-life traits, followed by body traits and feet and leg traits. Some traits associated with body size and foot angle differed between registered and grade cows. Estimates of genetic trends from obtained parameters revealed greatest progress for milk yield from single-trait selection but also the largest changes for some type traits and milk-corrected herd life in an undesirable direction. Relative milk to type ratios of between 2:1 and 3:1 yielded 90% of the gain in milk yield with no change or slight improvement in type traits and functional herd life. Selection for type traits associated with herd life appears to be warranted to improve days of functional herd life or to decrease involuntary culling of dairy cows.


Relationship between genetic merit of Holstein bulls and deficiency of uridine-5'-monophosphate synthase. Heterozygotes for a deficiency of uridine-5'-monophosphate synthase, a metabolic disease that interferes with pyrimidine biosynthesis, were related to a common ancestor, Skokie Sensation Ned. Predicted Differences of milk, fat, dollars, and protein from the July 1986 sire evaluation on 290 Holstein bulls born between 1975 and 1981 were analyzed for differences in the following groups: 5 heterozygous sons, 7 heterozygous grandsons, 5 normal sons, 20 normal grandsons of Ned, and a random sample of 253 normal bulls unrelated to Ned. From generalized least squares analysis, heterozygotes had higher estimates of genetic merit by 158 kg PD milk, 37 PD dollars, and 4.9 kg PD protein. Although an advantage was observed for heterozygotes within a family, descendants of Ned had lower estimates of genetic merit than their normal contemporaries. Sons of Ned had higher PD protein than grandsons of Ned, regardless of their uridine-5'-monophosphate synthase level. Propagation of the reproductively undesirable allele for deficiency of uridine-5'-monophosphate synthase should be controlled.


Increased cardiac awareness in panic disorder. We investigated cardiac perception in panic disorder with both self-report and objective measures. In Study 1, 120 patients with panic disorder, 86 infrequent panickers, and 38 patients with other anxiety disorders reported greater cardiac and gastrointestinal awareness than 62 normal control subjects. Subjects with panic attacks reported greater cardiac awareness, but not gastrointestinal awareness, than those with other anxiety disorders. Studies 2 and 3 included a test of heart rate perception in which subjects silently counted their heart-beats without taking their pulse. In Study 2, 65 panic disorder patients showed better performance than 50 infrequent panickers, 27 patients with simple phobias, and 46 normal control subjects. No group differences were found in ability to estimate time intervals. In Study 3, 13 patients with panic disorder and 15 with generalized anxiety disorder showed better heart rate perception than 16 depressed patients.


Psychological characteristics of dieters and bulimics. Two studies examined the continuum and discontinuity models of the relation between dieting and bulimia nervosa. In Study 1, 21 dieters, 19 bulimics, and 33 nondieting controls were compared on 24 measures. Multivariate analyses revealed that each of the groups differed significantly from the other two. Univariate analyses found 18 significant differences between bulimics and dieters and 1 significant difference between dieters and controls. In Study 2, 86 subjects completed measures of psychological functioning, dieting, and bulimia nervosa. On the basis of regression analyses using factor scores from the psychological variables as predictors, high scores on a psychopathology factor and low scores on a defensiveness factor predicted both bulimia and dieting. Low self-concept scores also predicted bulimia. These data indicate that both continuity and discontinuity characterize the relation between dieting and bulimia.


Relations among self-reported depressive symptoms in clinic-referred children versus adolescents. Although there is consensus regarding the existence of childhood depression, disagreement remains as to whether symptoms are developmentally isomorphic. Previous studies focused on developmental differences in symptom levels; analyses of relations among symptoms may be more appropriate, however. Here both approaches were used to compare the Children's Depression Inventory responses from 1,030 clinic-referred children and adolescents. Four of nine symptom categories showed significant developmental differences in their correlations with total score. Externalizing behavior and guilt were more strongly related to depression in children than adolescents; affective symptoms and concerns about the future showed the reverse pattern. Results illustrate the importance of considering relations among symptoms as well as differences in symptom levels when evaluating theoretical claims about developmental differences in the nature of clinical syndromes.


Increases in depressive symptomatology in the rural elderly: results from a cross-sectional and longitudinal study. Depressive symptomatology was examined in a large sample of noninstitutionalized older adults using the Center for Epidemiological Studies-Depression scale (CES-D). Both cross-sectional and longitudinal data showed age-related increases in mean CES-D scores and increases in the percentage of respondents scoring at or above the cutoff score of 16. Variables collected at baseline in the longitudinal study from 2,032 participants 65 years of age and older were significant predictors of depressive symptomatology 3 and 6 years later. Baseline CES-D scores accounted for the largest proportion of the variance.


Predictors and consequences of childhood depressive symptoms: a 5-year longitudinal study. A 5-year longitudinal study investigated the interrelationships among children's experiences of depressive symptoms, negative life events, explanatory style, and helplessness behaviors in social and achievement situations. The results revealed that early in childhood, negative events, but not explanatory style, predicted depressive symptoms; later in childhood, a pessimistic explanatory style emerged as a significant predictor of depressive symptoms, alone and in conjunction with negative events. When children suffered periods of depression, their explanatory styles not only deteriorated but remained pessimistic even after their depression subsided, presumably putting them at risk for future episodes of depression. Some children seem repeatedly prone to depressive symptoms over periods of at least 2 years. Depressed children consistently showed helpless behaviors in social and achievement settings.


Perceived-competence deficit in anorexia nervosa. Anorexia nervosa patients are portrayed as competent and accomplished and yet they feel ineffective and diffident. The assessment of this aspect of their self-esteem presents methodological problems. The Interests and Abilities Questionnaire was designed to measure interests and perceived abilities in typical adolescent activities. The disparity between interests and perceived abilities--perceived-competence deficit (PCD)--was hypothesized to be characteristic of anorexics. Three groups of females, aged 14 to 24, were studied: 13 anorexic inpatients, 13 psychiatric inpatients without an eating disorder but of similar severity of illness, and 48 nonclinical subjects. Similar to the nonclinical controls, anorexics were interested in a variety of activities; similar to control patients, anorexics rated their abilities lower than nonclinical subjects. In PCD, anorexics scored significantly higher than both control groups; this difference was not related to level of depression.


Factorial structure of traits delineating personality disorders in clinical and general population samples. Categorical and dimensional models for classifying personality disorders were evaluated by comparing the structure of personality pathology in a clinical sample (n = 158) with the structure in a general population sample (n = 274). Subjects completed 100 personality scales. Separate factor analyses revealed similar structures in the 2 samples. An underlying structure in a combined sample showed limited agreement with the concepts of the Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 1987). Fifteen factors were retained: Generalized Distress, Rejection, Restricted Expression, Compulsivity, Stimulus Seeking, Insecure Attachment, Diffidence, Intimacy Problems, Oppositionality, Interpersonal Disesteem, Conduct Problems, Cognitive Dysfunction, Affective Reactivity, Narcissism, and Social Apprehensiveness. The results are consistent with a dimensional representation of personality disorder.


Stepping through the drug use sequence: longitudinal scalogram analysis of initiation and regular use. Using a new technique for tracing the sequence of use over time, this study examined the pattern of drug involvement among 4,145 West Coast adolescents over the 4-year span from Grades 7-10. During the period covered, the mid- to late 1980s, we found no evidence that cocaine has become a gateway drug. However, the data provided some support for treating cocaine initiation as a separate stage that precedes the onset of hard drugs other than pills. The analysis also showed that increased involvement with legal drugs constitutes an important step in the transition to hard drug use for most adolescents. Weekly alcohol use followed marijuana use and preceded use of all other illicit drugs for Hispanic, White, and Black youth. However, it followed use of hard drugs for Asians. Weekly smoking formed a distinct stage between initial use of pills and other hard drugs for non-Hispanic Whites. The results underscore the importance of prevention efforts aimed at curbing the transition to regular use of alcohol and cigarettes, as well as their initial use.


Reaction to trauma: a cognitive processing model. We integrated existing cognitive processing models of posttrauma reactions into a longitudinal model. Data were obtained after a multiple shooting in a city office block. The subject group comprised 158 office workers who were in the building at the time of the shootings. The methodology of this research was a repeated measures survey, with data collection at 4, 8, and 14 months posttrauma. Measures included the Impact of Events Scale (IES) and the Symptom Checklist-90-Revised. A path analysis was performed with the IES as an indication of cognitive processing. Intrusion and avoidance were shown to mediate between exposure to trauma and symptom development. Intrusion was also found to be negatively related to subsequent symptom levels. The findings provide provisional support for a cognitive processing model.


Panic attacks in the nonclinical population: an empirical approach to case identification. Although self-reports of panic attacks are common among student populations, it is not clear that their panic experiences are actually comparable to those of patients with clinical anxiety disorders. An empirical approach was taken to this problem by using a cluster analysis procedure to identify subjects within two samples of university students who reported panic attack symptom profiles that resembled those of patients with panic disorder. Such empirically defined "clinical" panic attacks were reported by 7.0% and 8.1% of the two samples. This predominantly female group accounted for most of the increased psychopathology that has been reported in previous studies of nonclinical panic.


Proneness to shame, proneness to guilt, and psychopathology. The links between shame and guilt and psychopathology were examined. In 2 studies, 245 and 234 undergraduates completed the Self-Conscious Affect and Attribution Inventory, the Symptom Checklist 90, the Beck Depression Inventory, the State-Trait Anxiety Scale, and the Attributional Style Questionnaire. Results failed to support Lewis's (1971) notion that shame and guilt are differentially related to unique symptom clusters. Shame-proneness was strongly related to psychological maladjustment in general. Guilt-proneness was only moderately related to psychopathology; correlations were ascribable entirely to the shared variance between shame and guilt. Although clearly related to a depressogenic attributional style, shame accounted for substantial variance in depression, above and beyond attributional style.


Forms of memory failure in schizophrenia. Effortful and automatic memory task performances were examined in 36 schizophrenic patients and 18 normal control Ss. Tasks included free recall, recognition, and frequency estimation. Patients demonstrated impairment in recall, in recognition, in semantic encoding, and in frequency estimation. Deficits were observed across tasks despite differences in attentional demands. The results suggest a basic compromise of memory function, which is consistent with recent neuroimaging evidence of structural or physiological abnormalities in frontal and temporal lobe structures in schizophrenia.


Childhood depression and conduct disorder: I. Behavioral, affective, and cognitive aspects of family problem-solving interactions. We assessed the family interactions of depressed, conduct-disordered, mixed depressed-conduct-disordered, and nonclinic children, ages 7-14 years, during a standardized family problem-solving discussion in the clinic. The child's and the mother's problem-solving proficiency, aversive behavior, and associated affective behavior (depressed and angry-hostile) were observed. The child and mother also rated each other's affect during the interaction for the dimensions sad, angry, critical, and happy on Likert-type scales. The child's and mother's cognitive constructions about the interaction were assessed using video-mediated recall. Although all clinic groups had lower levels of effective problem solving than did nonclinic children, their deficiencies were somewhat different. Mixed and depressed children displayed high levels of depressed affect and low levels of angry affect, whereas conduct-disordered children displayed both angry and depressed affect. In addition, conduct-disordered children had lower levels of positive problem solving and higher levels of aversive content than did non-conduct-disordered children. Depressed and conduct-disordered children had higher levels of self-referent negative cognitions than did mixed and comparison children, and depressed children also had higher other-referent negative cognitions than did all other groups. The study provides support for theories and treatment that stress the importance of family problem-solving and conflict resolution skills in child psychopathology.


Childhood depression and conduct disorder: II. An analysis of family interaction patterns in the home. Few researchers have assessed family interaction patterns associated with childhood depression, especially using observations in natural settings. We directly sampled the interaction patterns of families with depressed, conduct-disordered, mixed depressed-conduct-disordered, and comparison children ages 7-14 years in their homes during the evening meal. Observational measures were taken of positive and aversive behaviors and affect expression for both parents, the referred children, and their siblings. Results replicated previous research showing that conduct-disordered children express high levels of aversive behavior and anger and are part of a family system marked by conflict and aggression. The depressed children were exposed to maternal aversiveness but did not show any evidence of elevated levels of anger or aversiveness in their own behavior. Surprisingly, this was also true for the mixed-disorder children. High levels of depression in both groups of depressed children were associated with low levels of conflict and anger in family members. Overall, siblings showed very similar patterns of behavior, and were exposed to similar patterns of parental behavior, as the referred children. Results are discussed in terms of family models that emphasize the function of aggression and depression in the maintenance of child psychopathology.


Longitudinal relationships among pain, sleep problems, and depression in rheumatoid arthritis. This research evaluated the relationship between pain and sleep problems, and the role of pain and sleep problems in depression, in a sample of 242 patients who had been diagnosed with definite or classical rheumatoid arthritis (RA). Patients completed the Pain scale of the Arthritis Impact Measurement Scales, the Center for Epidemiological Studies Depression Scale, and self-reports of sleep disturbance at two data waves over a 2-year interval. Cross-sectional multiple regression analysis revealed that the sleep problems variable was independently associated with depression at Time 1. Longitudinal multiple regression analyses demonstrated that prior pain predicted subsequent adverse changes in sleep problems, whereas sleep problems did not affect pain over time, and prior pain and the interaction of high pain and high sleep problems were independently associated with depression from Time 1 to Time 2. These data suggest that pain may exacerbate sleeping difficulty in RA patients, and that both factors may contribute to depression over time.


Reports of real and false memories: the relevance of hypnosis, hypnotizability, and context of memory test. Thirty high- and 30 low-hypnotizable subjects saw slides of a purse snatching and then imagined seeing the slides in hypnosis or waking conditions. The experimenter suggested the offender had a moustache (true), wore a scarf (false), and picked up flowers (false). Memory was tested by the experimenter after the suggestion, by another experimenter during an inquiry session, and again by the 2nd experimenter after the experimenter appeared to end the session. Hypnotizability, but not hypnosis, was associated with false memory reports; more high-than low-hypnotizable subjects reported false memories. The context of testing influenced true and false memory reports; fewer reports occurred in an informal rather than a formal test context.


Social factors and the psychobiology of depression: relations between life stress and rapid eye movement sleep latency. We examined psychosocial factors (i.e., life stress) and biological factors (i.e., REM sleep latency) that are hypothesized to be of complementary importance for defining depressive subtypes in a sample of 61 nonpsychotic, endogenous major depressives. Subjects were evaluated on several diagnostic scales for life stress, on electroencephalographic sleep data, and on 2 symptom measures for depression. As predicted, persons with severe stress that occurred shortly before depression onset had essentially normal REM latency values; patients without such stress had reduced REM latency values. Both stress and REM latency were also associated with greater severity of self-reported depressive symptoms. Alternative explanations of these findings are discussed, with particular emphasis on different roles of pre-onset and post-onset stressors.


Response to hyperventilation and inhalation of 5.5% carbon dioxide-enriched air across the DSM-III-R anxiety disorders. Anxiety disorder patients (n = 198; under criteria of the Diagnostic and Statistical Manual of Mental Disorders; rev. 3rd ed.; American Psychiatric Association, 1987) and nonanxious control subjects (n = 25) underwent challenges of 90 s of voluntary hyperventilation and 15 min of 5.5% carbon dioxide in air. Panic disorder subjects showed a greater subjective response to both challenges than did subjects with other anxiety disorders, who in turn responded more than did control subjects. Furthermore, subjects with panic disorder as an additional diagnosis tended to report more subjective response than did anxiety disorder subjects without panic disorder. The best prechallenge predictor of response to each procedure was a measure of fear of physical symptoms. The findings support previous results that have pointed to a greater fear or anxiety-inducing effect of these challenge procedures in panic disorder patients, as compared with other subjects.


DSM-III-R personality disorders and the five-factor model of personality: an empirical comparison. The relationship between the five-factor model (FFM) of personality and the Diagnostic and Statistical Manual of Mental Disorders (rev. 3rd ed.; DSM-III-R) personality disorders was examined in a sample of 54 psychiatric outpatients. Correlations between raw scores on the NEO-Personality Inventory (NEO-PI) and the number of DSM-III-R personality disorder symptoms rated present using a semistructured interview were computed. In addition, correlations between NEO-PI scores and scores on two self-report personality disorder inventories were also examined to determine which results replicated across instruments. Results indicated that the FFM personality dimensions of Neuroticism, Extraversion, and Agreeableness were most apparent in the DSM-III-R conceptualizations of the personality disorders.


Self-criticism in adulthood and recalled childhood experience. We investigated in a sample of 75 medical students the hypothesis that higher levels of self-criticism, a major vulnerability factor for depression, are related to retrospective reports of less satisfactory parenting, even when the potentially confounding factors of mood state and social desirability response set are controlled. At each of 2 measurement times, there were significant cross-sectional correlations between parental ratings and both depression and self-criticism, but the associations with self-criticism were no longer significant when depression was controlled. However, even after controlling for the effects of mood state and social desirability, persons with high levels of self-criticism at both measurement points (high trait self-criticism subjects) reported significantly worse relationships with their mothers than did the remaining subjects. They were also more likely to report below average relationships with both parents jointly.


Confirming the latent structure and base rate of schizotypy: a taxometric analysis. Meehl's (1962, 1990) model of schizotypy and the development of schizophrenia implies that the structure of liability for schizophrenia is dichotomous and that a "schizogene" determines membership in a latent class, or taxon (Meehl & Golden, 1982). The authors sought to determine the latent structure and base rate of schizotypy. They applied Meehl's (1973; Meehl & Golden, 1982) MAXCOV-HITMAX taxometric analytic procedures to a subset of items from the Perceptual Aberration Scale (PAS; Chapman, Chapman, & Raulin, 1978), a prominent psychometric index of schizotypy, derived from a randomly ascertained nonclinical university sample (N = 1,093). The results, in accordance with Meehl's conjectures, strongly suggest that schizotypy, as assessed by the PAS, is taxonic at the latent level with a general population taxon base rate of approximately .10.


Clinical depression and implicit memory. We investigated performance on implicit and explicit memory tasks in subjects diagnosed with major depression and matched controls. Depressed subjects showed impaired performance on both the explicit and implicit tasks in comparison with controls. These findings are in contrast to groups such as amnesic patients and older adults, who show preserved abilities on implicit tasks and deficits on explicit tasks.


Affective valence and memory in depression: dissociation of recall and fragment completion. Depressed (n = 16) and nondepressed (n = 16) subjects' memory for affectively valenced words was assessed by an explicit test (free recall) and an implicit test (word fragment completion). Under free-recall instructions, depressed subjects recalled significantly more negatively valenced than positively valenced words, whereas the opposite pattern was observed in nondepressed control subjects. These results replicate those previously reported in the literature. The differential effect of word valence was absent, however, when memory was tested implicitly: Depressed and nondepressed subjects exhibited equivalent priming of positive and negative words. These data are discussed in terms of Williams, Watts, MacLeod, and Mathews's (1988) model of depression.


Mood-congruent memory in depression: emotional priming or elaboration? We investigated whether mood-congruent memory (MCM) bias in depression is a function of implicit or explicit memory. Implicit memory is taken as a measure of ease of activation, whereas explicit memory also taps elaboration. As expected, MCM bias was found in the explicit memory task but not in the implicit memory task. We believe this finding supports the involvement of elaborative mechanisms in MCM. In addition, memory bias was found with words related to depression but not with words denoting physical threat. Thus, the MCM bias in explicit memory was found to be specific to information that was congruent with depression rather than to all negative information.


Depression and implicit memory: a commentary. In this invited commentary, we review four studies in which the issue of whether depression affects priming on implicit memory tests was examined. We conclude that a depressive mood does not affect amount of priming on several implicit memory tests under conditions in which marked effects are shown on conscious recollection (explicit memory). The mood congruity effect (depressives remember depression-related words better than controls; controls remember other types of material better than depressives) also largely disappears on perceptual implicit memory tests. We speculate about reasons for discrepancies in the literature, relate the findings to some current theories of individual differences in memory, and suggest some directions for future research.


Nightmare frequency versus nightmare distress: relations to psychopathology and cognitive style. The hypotheses that psychopathology is related to nightmare distress but not nightmare frequency and that cognitive style is related to nightmare frequency were examined. The sample consisted of 85 subjects (58 women and 27 men) who completed several measures: a sleep and dream inventory, Symptom Check List-90-R, Fear Survey Schedule-II, Beck Depression Inventory, an abbreviated version of the Harvard Group Scale of Hypnotic Susceptibility, Vividness of Visual Imagery, an absorption scale, a social desirability scale, and the Boundaries Questionnaire. The results strongly support the first hypothesis but only slightly the second. Such findings underscore the need to differentiate nightmare frequency from suffering (waking distress associated with nightmares) and suggest that although frequency may be related to an intensification of dreaming process, suffering is related to waking emotional adjustment.


A new radioimmunoassay using a commercially available solid support for the detection of IgE antibodies against muscle relaxants. It is well established that muscle-relaxant drugs may be responsible for anaphylactoid reactions during anesthesia. In this study, we developed an in vitro test with a commercially available solid phase for the detection of specific IgE directed to the tertiary or quaternary ammonium groups of neuromuscular-blocking drugs. The solid-phase complex was P-aminophenylphosphoryl-choline (PAPPC) immobilized on agarose, and an RIA was performed with an antihuman IgE labeled with 125I. The results, expressed as the percentage of 125I-labeled anti-IgE linked to the solid phase, were at 0.41 +/- 0.19 for 34 control sera from nonallergic healthy adults, with an upper limit estimated at 1%. The values obtained with the sera of 31 allergic patients ranged from 0.6% to 41% with a sensitivity of 97%. The specificity and the positive predictive value of the PAPPC RIA were 97% and 94%, respectively. These results were compared with results of other RIAs with morphine, trimethylamine, triethylamine immobilized on epoxy-activated Sepharose, and choline hydrochloride immobilized on Sepharose (quaternary ammonium Sepharose RIA) and with Phadebas RAST succinylcholine and Phadebas RAST alcuronium. The PAPPC RIA appears to be the most efficient test to screen sera for the presence of IgE antibodies directed to neuromuscular-blocking drugs. One major advantage is that this solid phase is commercially available and ready to use. This advantage will improve the accuracy in the comparison of the results with results from different laboratories.


The effect of recombinant human interleukin-5 on eosinophil accumulation and degranulation in human nasal mucosa. Recombinant human interleukin-5 (rhIL-5) was administered repeatedly onto the nasal mucosa of individuals with Japanese cedar pollinosis outside the pollen season. The numbers of eosinophils and epithelial cells and the amount of eosinophil cationic protein (ECP), secretory IgA (S-IgA), and IgA in the nasal lavage fluid increased significantly after the application of rhIL-5. Responsiveness to histamine was also enhanced after the application. When S-IgA was administered onto the nasal mucosa after application of rhIL-5, the amount of ECP in the nasal lavage fluid was significantly more increased. The above findings together with the facts that IL-5 promotes production of IgA, that IgA receptors are present on eosinophils, and that rhIL-5 does not increase release of ECP from eosinophils isolated from the peripheral blood suggest that a series of possible reactions consisting of (1) IL-5--induced production of IgA from the immune-mediating cells, (2) binding of secretory components released from either serous glandular cells or epithelial cells of the nasal mucosa with IgA, (3) release of ECP from eosinophils induced by S-IgA and/or IgA, (4) epithelial damage to the nasal mucosa, and (5) development of nasal hyperreactivity to histamine.


In vivo expression of CD69 on lung eosinophils in eosinophilic pneumonia: CD69 as a possible activation marker for eosinophils. The antigen, CD69, has been demonstrated to be expressed on activated T cells and natural killer cells. There have been no studies concerning the expression of CD69 on eosinophils. In this article, we demonstrate that lung eosinophils obtained from the bronchoalveolar lavage fluid of patients with eosinophilic pneumonia expressed significant levels of CD69, whereas peripheral blood (PB) eosinophils did not express CD69. We also activated PB eosinophils in vitro using phorbol myristate acetate and cytokines to determine whether CD69 was expressed. PB eosinophils expressed CD69 after short-term culture with phorbol myristate acetate and eosinophil hemopoietic cytokines (interleukin-3, granulocyte-macrophage--colony-stimulating factor, and interleukin-5). These findings suggest that CD69 may be a useful marker for activated eosinophils at inflammatory sites.


Imported fire ant immunotherapy: effectiveness of whole body extracts. The purpose of this study was to determine if whole body extract (WBE) immunotherapy for imported fire ant (IFA) hypersensitivity is effective. This evaluation was carried out by retrospectively interviewing 76 patients with a history of generalized allergic reactions to IFA stings and positive skin tests to IFA-WBE. The study groups consisted of 65 patients on immunotherapy and 11 similar patients who were not treated for various reasons. In addition, an IFA sting challenge was performed in 30 volunteers of the 65 patients on immunotherapy. The retrospective review showed that of the 65 patients on immunotherapy there had been 112 subsequent field-sting episodes in 47 patients. Only one sting episode in this group (2.1%) produced an anaphylactic reaction. Six of the 11 patients not on immunotherapy have had subsequent field re-sting episodes, and each has had a systemic reaction. Repeat skin testing on 31 of the 65 patients in the immunotherapy group showed persistent positive responses in five (16%), but each was at a lower dilution than initially. Responses of the other 26 of the 31 patients who had skin testing had become negative. The four untreated patients who were available for skin testing continued to have positive responses at comparable dilutions on skin testing. Sting challenges carried out on 30 volunteers from the 65 patients (all from the 31 who had repeat skin tests) on immunotherapy resulted in only local reactions.(ABSTRACT TRUNCATED AT 250 WORDS)


Serum IgE in nonatopic smokers, nonsmokers, and recent exsmokers: relation to lung function, airway symptoms, and atopic predisposition. The influence of smoking on serum IgE (s-IgE) was studied in a selected nonatopic population. The variation in s-IgE was followed during 1 year of smoking abstinence. The study included 287 smokers and 137 never smokers. IgE was higher in smokers compared with IgE in never smokers (p less than 0.005). Male smokers had higher s-IgE than female smokers (p less than 0.01). S-IgE was independent of age and claims of atopy among first-degree relatives. Weighted pack-years consumption was defined for cigarette smokers by modifying pack-years consumption by nicotine content of the brand smoked. Weighted pack-years consumption was associated with level of s-IgE (p less than 0.05). S-IgE was higher in smokers with airway symptoms compared with that in smokers without symptoms (p less than 0.01). In smokers older than 50 years of age, there tended to be decreased FEV1 residuals (0.05 less than p less than 0.06), and presence of airway symptoms was (p less than 0.03) associated with high levels of s-IgE independent of each other. In 92 quitters, s-IgE increased during the first 26 weeks of abstinence (p less than 0.05), and after 1 year, s-IgE had returned to baseline. The increase was only observed in smokers younger than 40 years and had no relation to variations in FEV1 during the 1-year follow-up. The increase in s-IgE after smoking cessation was transient, of minor clinical importance, and probably caused by a relief from an immunosuppressive influence.


Characterization of latex antigens and allergens in surgical gloves and natural rubber by immunoelectrophoretic methods. Allergy to natural rubber (latex) products is increasingly frequent among both medical personnel and lay subjects. Although individual antigens and allergens in latex products have not been fully characterized, they are believed to derive from the sap of the rubber tree. Rabbit IgG and human IgE antibodies against rubber proteins were used to characterize antigens and allergens in surgical latex gloves and natural rubber by crossed immunoelectrophoresis and its modifications. The results from crossed-line immunoelectrophoresis demonstrated that the surgical latex gloves had at least 10 antigens in common with natural rubber sap and ammoniated latex. In crossed radioimmunoelectrophoresis, at least six of the 10 protein antigens in the surgical glove extract and natural rubber were allergens since they bound IgE antibodies from the latex-allergic patients' sera. The surgical glove extract also demonstrated one allergen not found in natural rubber, suggesting that rubber proteins may be altered during glove manufacture.


Effect of environmental factors on the development of allergic disorders in infancy. A total of 1167 infants were followed for 1 year in a population-based prospective study to assess the effect of environmental factors on the development of allergic disorders. Some of these environmental factors are interdependent. Mothers who formula fed their infants smoked more often (p less than 0.001) and tended to belong to lower social classes (p less than 0.01). Logistic regression analysis was performed to adjust for these confounding variables. Maternal smoking adversely affected the prevalence of asthma (p = 0.003) defined as three or more separate episodes of wheezing and total allergy (p = 0.02). Infants in lower socioeconomic groups developed asthma significantly more often (p = 0.03) than infants born in higher socioeconomic groups. There was a nonsignificant trend for infants born in summer to develop asthma more than infants born in winter (p = 0.08). No effect of these factors was observed on eczema, food intolerance, or on the subgroup of infants with definite allergy (clinical disorder with positive skin prick test [SPT]). Exposure to animal dander did not influence the prevalence of clinical disorder, but positive SPT reaction to cat dander was more prevalent in infants who were exposed to cats and/or dogs (p = 0.04). Positive SPT to house dust mite occurred significantly more often in infants who were formula fed (p = 0.05). The environmental factors had a profound effect on the prevalence of asthma but not on other allergic disorders.


Nasal beclomethasone prevents the seasonal increase in bronchial responsiveness in patients with allergic rhinitis and asthma. Experimental studies have demonstrated that induction of a nasal allergic reaction can lead to an increase in bronchial responsiveness (BR). To assess the clinical relevance of these experimental changes to chronic asthma, we sought to determine the effect of nasal beclomethasone dipropionate (Bdp) on BR in patients with seasonal allergic rhinitis and asthma. Eighteen subjects with histories of seasonal allergic rhinitis and asthma during the fall pollen season with positive skin tests to short ragweed and bronchial hyperresponsiveness to inhaled methacholine were assigned to receive either nasal Bdp (336 micrograms/day) or placebo for the entire ragweed season. Patients recorded daily nasal and chest symptoms, nasal blockage index, oral peak expiratory flow rates, and supplemental medication use. BR to methacholine was measured during the baseline period and 6 weeks into the ragweed season. Although the Bdp group did have a significant improvement in nasal blockage index, there was no improvement in daily asthma symptom scores, oral peak expiratory flow, or asthma medication use. However, subjects treated with Bdp were protected from the increase in BR seen in the placebo group (geometric mean PC20 placebo group: baseline = 0.70, week 6 = 0.29; Bdp group: baseline = 0.80, week 6 = 0.93; intergroup difference, p = 0.022). We conclude that nasal corticosteroid therapy can prevent the increase in BR associated with seasonal pollen exposure in patients with allergic rhinitis and asthma.


Treatment of peanut allergy with rush immunotherapy. Peanut and peanut products are a common food in the diet. Peanuts are also one of the most common foods responsible for food-induced anaphylaxis. Patients rarely lose sensitivity to peanuts. Although the ideal treatment is avoidance, this is often not possible because of hidden exposures; therefore, a more effective treatment is needed. Subjects with confirmed peanut allergy were treated in a double-blind, placebo-controlled study with peanut immunotherapy or placebo. Objective measures of efficacy included changes in symptom score during double-blind placebo-controlled peanut challenge (DBPCPC) and titrated end point prick skin tests (PST). Three subjects treated with peanut immunotherapy completed the study. These subjects displayed a 67% to 100% decrease in symptoms induced by DBPCPC. Subjects also had a 2- to 5-log reduction in end point PST reactivity to peanut extract. One placebo-treated subject completed the study. This subject had essentially no change in DBPCPC symptom scores or PST sensitivity to peanut. Two other placebo-treated subjects underwent a second PST session. These subjects had a 1- to 2-log increase in skin test sensitivity to peanut. All peanut-treated subjects were able to reach maintenance dose, and in no case did an anaphylactic reaction occur secondary to the peanut immunotherapy. The current study provides preliminary data demonstrating the efficacy of injection therapy with peanut extract and provides a future line of clinical investigation for the treatment of this potentially lethal disease. It should be noted, however, that the rate of systemic reactions with rush immunotherapy was 13.3%.(ABSTRACT TRUNCATED AT 250 WORDS)


Fetal dexamethasone exposure accelerates development of renal function: relationship to dose, cell differentiation and growth inhibition. Fetal exposure to high doses of glucocorticoids slows cellular development and impairs organ performance, in association with growth retardation. Nevertheless, low doses of glucocorticoids may enhance cell differentiation and accelerate specific functions. The current study examined this apparent paradox in the developing rat kidney, using doses of dexamethasone that span the threshold for growth impairment: 0.05 or 0.2 mg/kg given on gestational days 17, 18 and 19. At the lower dose, which did not significantly retard body growth, the postnatal development of tubular reabsorptive capabilities for sodium, potassium, osmotic particles, water and urea was accelerated. These effects were less notable at the higher dose, which caused initial body growth impairment. The selectivity toward promotion of tubular function was evidenced by the absence of effect of either dose of dexamethasone on development of glomerular filtration rate. Because of the wide spectrum of dexamethasone's effects on tubular function, we also assessed fetal kidney adenylate cyclase as a means of detecting altered cell differentiation in the prenatal period during which dexamethasone was given. Either glucocorticoid dose increased the total adenylate cyclase catalytic activity (assessed with forskolin). Thus, the net effect of fetal dexamethasone exposure on development of renal excretory capabilities probably represents the summation of promoted cell differentiation and slowed development consequent to growth retardation. At low dose levels, the former effect predominates, leading to enhanced functional development, whereas higher doses that interfere with general growth and development can offset the direct promotional effect.


Prostaglandin production in the umbilical and uterine circulations in pregnant sheep at 129-136 days gestation. Prostaglandins circulating in the maternal and foetal blood have been implicated in important physiological systems. These functions include foetal adrenal function, maintenance of patency of the ductus arteriosus, regulation of uterine and umbilical circulations, and labor and delivery type myometrial contractions. The placenta is a major site of prostaglandin production in pregnancy. Limited data are available which combine measurements of veno-arterial differences across the uterine and umbilical circulations with blood flow in these circulations to enable calculation of umbilical-placental and utero-placental production rates for the prostaglandins. In chronically instrumented pregnant ewes, between 129 and 136 days of gestation, prostaglandin F2 alpha(PGF2 alpha), 13, 14 dihydro-15-keto prostaglandin F2 alpha (PGFM), prostaglandin E2 (PGE2) were measured in the maternal carotid artery and uterine vein. Foetal PGE2, and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) (the major metabolite of prostacyclin) were measured in umbilical venous and foetal descending aorta arterial plasma. Umbilical and uterine blood flow were measured using the diffusion-equilibrium technique. Uterine blood flow was 1693 +/- 137 ml.min-1 (mean +/- SEM); uterine production rates were 480 +/- 88 ng.min-1 for PGF2 alpha, 517 +/- 144 ng.min-1 for PGFM, and 165 +/- 27 ng.min-1 for PGE2. Umbilical blood flow was 147 +/- 17 ml.min-1.kg-1 foetal body weight. Umbilical production rates into the foetal circulation were 11 +/- 2 ng.min-1.kg-1 for PGE2 and 6 +/- 2 ng. ng.min-1.kg-1 foetal body weight for PGI2.


Foetal circulatory responses to arrest of uterine blood flow in sheep: effects of chemical sympathectomy. Acute foetal asphyxia, caused by arrest of uterine blood flow, increases both sympathetic activity and peripheral vascular resistance and decreases blood flow to peripheral organs (Jensen et al., J. Dev. Physiol., 9, 543-559). The rapidity and uniformity of this peripheral vasoconstriction suggest that the sympatho-neuronal system may reflexly cause these initial blood flow changes during acute asphyxia. To test this hypothesis, we studied 5 intact and 6 chemically sympathectomized (6-hydroxy-dopamine, 46.1 +/- 6 mg/kg foetal weight) chronically prepared normoxaemic foetal sheep in utero at 0.9 of gestation. Organ blood flows (microsphere method), plasma concentrations of catecholamines, vasopressin, and angiotensin II, acid-base balance and blood gases were measured before, during and after arrest of uterine blood flow for 2 min, i.e., at 0, 1, 2, 3, 4 & 30 min. In intact foetuses there was a progressive increase in arterial blood pressure and a rapid circulatory centralization in favour of the brain stem and heart and at the expense of most of the peripheral organs. The changes in peripheral blood flow during and after asphyxia were well reflected by those in the skin and scalp. In chemically sympathectomized foetuses, arterial blood pressure fell transiently at 1 min of asphyxia and cardiac output was redistributed towards the carcass and intestinal organs at the expense of the heart, spinal medulla, and placenta. We conclude that in foetal sheep at 0.9 of gestation, the short-term adaptation to arrest of uterine blood flow is a rapid and profound peripheral vasoconstriction to effect an increase in arterial blood pressure. This initial response during circulatory centralization, which is necessary to increase or maintain blood flow to the heart, brain stem, and placenta, is blunted by sympathectomy. Thus, the foetal sympatho-neuronal system is important for short-term adaptation to and intact survival of asphyxia.


A modified helium dilution technique for measuring small lung gas volumes. The present study was undertaken to devise an accurate method for measuring functional residual capacity, FRC, in small and lively newborn animals such as lambs and piglets under flexible laboratory conditions using relatively simple equipment. This was achieved by adapting the standard helium dilution method so that FRC could be calculated from the helium equilibration concentration reached when the subject, having breathed a gas mixture with a high helium concentration, rebreathed from an air-filled spirometer. Using this technique, typical results for test volumes of 10, 20, 30 and 40 ml were measured as 10.7 +/- 0.34, 20.2 +/- 0.19, 30.5 +/- 0.40 and 40.6 +/- 0.75 ml respectively with corresponding coefficients of variation of 6.4%, 1.9%, 2.6% and 3.7%. Repeat measurements made on each of 3 urethane anaesthetised rabbits gave values for FRC of 45.64 +/- 0.9 ml (5 measurements), 37.22 +/- 0.8 ml (8 measurements) and 48.95 +/- 0.99 ml (8 measurements) confirming the reproducibility of results from animal preparations. The FRC of newborn lambs (12 animals) was 81.4 +/- 9.2 ml. The technique also allowed clear recordings of respiratory pattern essential to the analysis of variations in FRC.


Ion transport regulation of lung liquid secretion in foetal lambs. To test the hypothesis that liquid formation in the foetal lung reflects the balance between Cl- secretion and Na+ absorption by the respiratory tract epithelium, we studied the independent and combined effects of selective ion transport inhibitors on basal production of lung liquid in foetal lambs. We prepared 19 foetal lambs (gestation 125 +/- 4, term = 147 days) with chronic indwelling catheters for subsequent measurement of luminal liquid production over time (JV). Using an impermeant tracer technique, we measured JV before and after tracheal instillation of 2 different inhibitors of ion transport: bumetanide, a Na(+)-K(+)-2Cl- co-transport inhibitor, and amiloride, a Na+ transport inhibitor. In 7 foetuses we sequentially added bumetanide (10(-4) M) and 2 different concentrations of amiloride (10(-6) M, 10(-4) M) to the liquid within the lung lumen. After we gave bumetanide, JV decreased from 12 +/- 4 ml/h to 0 +/- 5 ml/h and subsequently increased during the 2 periods of amiloride exposure (10(-6) M: 6 +/- 5 ml/h; 10(-4) M: 7 +/- 7 ml/h). In 5 control studies we gave bumetanide, followed by only amiloride vehicle. JV for all time periods in the control studies was similar to the experimental group, demonstrating no effect of amiloride. In 5 foetuses we administered the 2 concentrations of amiloride before bumetanide. There was no change in JV with either concentration of amiloride (baseline: 13 +/- 2 ml/h; 10(-6) M amiloride: 15 +/- 5 ml/h; 10(-4) M amiloride: 13 +/- 6 ml/h).(ABSTRACT TRUNCATED AT 250 WORDS)


Campylobacter jejuni bacteraemia in children with diarrhoea in Bangladesh: report of six cases. Campylobacter jejuni was isolated from blood cultures from 6 of 6,275 diarrhoeal children seeking treatment at the Clinical Research Centre of the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B) between April 1989 and December 1990. The clinical records of these 6 children were reviewed. All children were male; 5 were less than 1-year old and were severely malnourished. Five patients presented with watery diarrhoea and one with bloody diarrhoea. Two children died in the hospital. All strains of Campylobacter isolated from the 6 children were negative for cell invasive properties as tested by the Sereny test. Of the two strains tested for serum bactericidal activity, one strain was serum sensitive (growth inhibition), and the other resistant. The ability of C. jejuni to cause bacteraemia suggests that the organisms may be responsible for diarrhoeal diseases especially in young and malnourished children. An early attempt to detect Campylobacter and start effective antimicrobial therapy is indicated.


Cholera epidemics in Bangladesh: 1985-1991. In 1991, a major epidemic of diarrhoea broke out in Bangladesh. To estimate the extent of cholera during diarrhoea epidemics and to focus on the public health issues related to cholera in Bangladesh, we have used the government figures of the 1991 epidemic and data from our own experience of epidemic interventions in nearly 400 rural upazilas (sub-district) between 1985 and 1989 and in 1991. Our data showed that V. cholerae 01 was the most frequently (40%) isolated enteropathogen during the epidemics. The disease is widely distributed in the country. Only 24% of the total 1,648 laboratory confirmed cholera patients were below 5 years of age, and children below 2 years of age accounted for only 10% of the total. Access difficulty to medical care and absence of a reliable surveillance were thought to be the constraints to early detection and appropriate intervention, thus, there were more deaths during the epidemics. We have shown that a high proportion (59%) of cholera patients during their illness in the rural areas were not visited by the government surveillance staff and that most (80%) were treated at home. Access to treatment by qualified physicians was limited to 23% of the patients, whereas a large proportion of the patients were treated by the unqualified rural practitioners (68%), and the others (9%) had no access to any health care providers. Our experience also indicated a higher case fatality ratio (14%) prior to intervention by qualified physicians during epidemics and an overall fatality ratio of 4%, despite the significant reduction (less than 1%) achieved by the intervention. Cholera is highly epidemic in Bangladesh.(ABSTRACT TRUNCATED AT 250 WORDS)


Colonisation with digoxin-reducing strains of Eubacterium lentum and Clostridium difficile infection in nursing home patients. Stool specimens obtained from 77 residents of a nursing home were analysed to determine the relationship between colonisation with digoxin-reducing strains of Eubacterium lentum and infection with Clostridium difficile. Patients were categorised according to previous antibiotic treatment, prescription of enteral feedings, and pattern of bowel habits. Colonisation with digoxin-reducing E. lentum was less common in subjects infected with C. difficile, in those treated with antibiotics previously, and in those prescribed enteral feedings. Normal bowel habits were more common in those without C. difficile. The lowest incidence of diarrhoea was seen in patients without C. difficile who were colonised with digoxin-reducing species. This study establishes an inverse relationship between the presence of C. difficile and E. lentum that reduce digoxin which is related to previous treatment with antibiotics and prescription of enteral feedings. Bacterial markers may prove to be a useful tool for predicting clinical disturbances in bowel function.


Conjugal transferability of multiple antibiotic resistance in three genera of Enterobacteriaceae in Nigeria. Ninety-eight enteric bacteria were isolated from stool samples of 3,000 diarrhoeal patients during 1988-1989 in Ibadan, Nigeria. The isolates were: 20 Salmonella, 28 Shigella and 50 Escherichia coli. S. typhi and S. Flexneri were most prevalent while serotypes 055, 026 and 0128 were most common among the E. coli. Eight resistance patterns to ampicillin (Ap), streptomycin (Sm), tetracycline (Tc) and chloramphenicol (Cm), the four commonly used drugs in this environment were observed in the isolates. Resistance to all four drugs was common in the Shigella isolates. Conjugation experiments showed that 92% of the isolates tested were able to transfer all or part of their resistance to the recipient E. coli. The Salmonella and Shigella isolates were more efficient in this respect as all the isolates tested (100%) transferred all or part of their resistance character. Ability of the latter two genera to transfer the Ap, Sm, Tc, Cm complete linkage might be enhanced by using more efficient recipient or by mobilisation. Control of antibiotic usage and improvement of personal hygiene were recommended to prevent the spread of drug resistance among the enteric pathogens.


Deciding on access and levels of care: a comparison of Canada, Britain, Germany, and the United States. Americans view universal coverage as a reality only if a minimum benefit package is explicitly defined, and discussions about expanding access take place under the slogan of minimum benefits. The policy environment is different in Canada, Britain, and Germany. There, health care costs are controlled and benefits provided under universal coverage plans. Yet the medical services provided in these countries result not from difficult decisions about rationing care at a "minimum" benefit level but from difficult political decisions about the structure of the health care system. Institutional factors rather than explicit policy influence the implicit health priorities in these countries. The United States, in contrast, develops policies that explicitly designate a minimum level of benefits.


Privatization in health and human services: a critique. Privatization currently enjoys wide appeal as a solution to public problems. Supporters of privatization hope that shifting responsibility for the funding, administration, and delivery of services to private organizations and individuals will spur market competition and thus lower costs, improve service effectiveness, and enhance program quality. An increasingly common form of privatization in health and human services is contracting with nonprofit organizations. Such contracting, in practice, does not follow market principles but is, instead, fraught with politics and inadequate information and built on long-term relationships between government and contract agencies. The operations and practices of contracting have important implications for the ongoing debate on the desirability of vouchers for health care insurance and for reform in the contracting process.


The subsidy provided under Medicare to current enrollees. Contributions made by or for current enrollees to Medicare will cover less than a third of the costs of their expected lifetime benefits, on average. This subsidy is of concern for two reasons. First, because the subsidy is provided regardless of income, some transfers are effectively made to Medicare enrollees from needier groups in the non-Medicare population. Second, as the ratio of Medicare beneficiaries to the working-age population increases in future years, the current generosity of the program may be difficult to maintain.


Medicaid and access to child health care in Chicago. In this article we examine how increasing the reimbursement of physicians and expanding Medicaid eligibility affect access to care for children in Cook County, Illinois, which overlies Chicago. Using Medicaid claims and other data at the zip-code level, we compare the places where Medicaid children live with the places where all the physicians who treat children and those who accept Medicaid patients have their practices. Our findings suggest that the recent changes in legislation are unlikely to benefit extremely poor children, who are more likely to live in depressed inner-city areas, where there are few physicians. "Near-poor" children whose homes are dispersed throughout the county, who are now eligible for Medicaid as a result of the recent changes, are likely to see improvements in their access to care. Further changes in policy, aimed at enhancing the capacity of institutions providing care, could improve access for the children of the inner city.


A blip on the radar screen: formulation and implementation of the Medical Waste Tracking Act. We use the passage and implementation of the Medical Waste Tracking Act of 1988 (MWTA) to explore the implications of health and environmental policies that are formulated in the context of events defined politically as a crisis. Building on Kingdon's (1984) "garbage can" model of policy initiation, we assess the linkage between a policy environment that provides strong but short-lived support for the enactment of a policy and its subsequent implementation. Among the implications of the less-than-impressive substantive results of the MWTA is the lesson that while a crisis can tilt the political balance in favor of regulatory legislation, it cannot as readily produce the consensus required to sustain that regulation at the levels promised in the legislation.


Philip Morris's failed experiment in Pittsburgh. The campaign for passage and implementation of Pittsburgh's Smoking Control Ordinance in 1987 illustrates the role controversy plays in tobacco control. Proponents of the ordinance sought at first to keep it noncontroversial, while the tobacco industry tried to defeat the ordinance by generating controversy, claiming that severe economic and social disruption would occur. After the ordinance had been in force for a year, Philip Morris tried to take over its implementation, seeking to redefine the central issue as one of social accommodation rather than health. To succeed, Philip Morris's effort had to be widely accepted and noncontroversial. Proponents of the ordinance countered with controversy to undermine the campaign and expose the company's intentions. The controversy made the established health organizations uncomfortable, causing them to play only a marginal role. Surprisingly, the people who prevailed were the nonsmokers' rights activists, a small group with limited resources.


Factors influencing first relapse in patients with Crohn's disease. To determine whether information available at time of diagnosis of Crohn's disease can predict initial clinical course, I followed 239 patients prospectively from time of diagnosis to initial relapse. The patient's sex, smoking habits, contraceptive usage, disease extent, and presence of granulomas in the first histological specimen were recorded. No association was found between this demographic data and the interval between onset of symptoms and diagnosis, the severity of symptoms at presentation, or the time to relapse. The type of relapse, however, was influenced by the type of the first attack; 70% of relapses were of the same type as the initial attack. Cigarette smoking was associated with ileocolitis (p = 0.028). There was a trend for oral contraceptive users to have ileocolitis, whereas the presence of granulomas in the first histological specimen was not associated with a specific disease distribution. Patients with ileocolitis had more inflammatory attacks than those with ileitis or colitis (p = 0.001). There was also a trend for cigarette smokers and those on oral contraceptives to have more inflammatory attacks, but the presence of granulomas had no effect on the type of relapse. There is little to assist in prognosis of early disease when the diagnosis of Crohn's disease is first made, although the types of attacks tend to repeat themselves.


Achalasia: new thoughts on an old disease. Achalasia is the most recognized esophageal motor disorder first described 300 years ago by Sir Thomas Willis. Although the cause of achalasia remains unknown, the disease is thought to occur as a result of degeneration of Auerbach's plexus in the intramural nervous network. A review of the literature reveals that there is reversibility of this disease in some patients after treatment, raising intriguing questions as to the pathogenesis of this disorder and underscoring the need for further study.


Uninhibited anal sphincter relaxation syndrome. A new syndrome with report of four cases. I report a new syndrome, in four patients, all male. Patients ranged from 36 to 43 years of age. The main complaint was fecal urgency with occasional fecal soiling. Physical examination as well as pressure and EMG studies of anal sphincters and levator ani muscle were all normal. The only positive finding was an abnormal rectoinhibitory reflex. The external anal sphincter did not contract either reflexively or voluntarily on rectal distension, leaving the relaxing internal sphincter unprotected and uncontrolled. The patients could not oppose the urge to defecate if conditions are inopportune, with resulting urgency and occasional fecal soiling. The cause is unknown, but biofeedback effected improvement in all four cases.


Does a risk questionnaire add anything to a colorectal screening project? Report of a 3-year screening experience. A questionnaire to detect persons at high risk for colorectal cancer was used in conjunction with fecal occult blood tests in a 3-year screening program in Northern Israel. Screening was offered to 2,590 persons over 40 years of age and accepted by 1,797 (compliance of 69.4%). In the subsequent 2 years, occult blood testing (Hemoccult II) was offered to those who had had negative tests (compliance rate of 99.6% and 100%). Six hundred and thirty persons (35.1%) had risk factors according to the questionnaire, and 195 of them underwent colonoscopy, with a predictive value of 15.9% for a neoplastic lesion. The Hemoccult II test was positive in 71 participants (4.0%) of whom 67 were investigated with a similar predictive value for neoplastic lesion (16.4%). In the second and third annual screening, the fecal occult blood test was positive in 29 (2.6%) and 27 (2.5%), and had a two and three times higher predictive value for neoplastic lesions, respectively. This was accompanied by a decrease in the cost of discovery. In all three stages, an adenomatous polyp was found in 48, and cancer in 10 participants (2.6% and 0.5% of the 1,797 original participants). Although a questionnaire may be fruitful in colorectal cancer screening, the higher number of participants subjected to further examinations makes this approach very expensive. The annual stool examination for occult blood has a higher predictive value for colonic neoplasm and a lower cost than a one stage, broader population based, study.


Calcium and acid rebound: a reappraisal. We review acid rebound, the seemingly paradoxical increase in acid secretion resulting from administration of an antacid. Primarily a laboratory observation, the demonstration of the phenomenon was a major contributing factor to the swift, and possibly unjustified, fall from grace of calcium carbonate in the therapy of peptic ulcer disease despite years of apparently successful use. Calcium, as carbonate or other salts, causes an increase in gastric acid secretion owing, at least in part, to direct ionic stimulation. Another possible mode of action involves antral alkalinization with subsequent gastrin release. Other antacids, notably magnesium hydroxide and aluminum hydroxide, may therefore also cause rebound, but the data in this area are less convincing. Despite the demonstration that acid rebound occurs, no one has thoroughly investigated its clinical import. What limited data actually exist suggest no obvious clinically significant deleterious effect from use of calcium carbonate in peptic ulcer. Because of calcium carbonate's excellent acid-neutralizing capacity, its venerable past record in treating ulcer disease, and recent observations that low-dose antacids heal peptic ulcers, it is appropriate to reevaluate acid rebound, to focus on its clinical significance, if any.


Collagenous enterocolitis: a manifestation of gluten-sensitive enteropathy. We report coexistent collagenous colitis and collagenous sprue in a 62-year-old woman with diarrhea. Investigations suggested malabsorption, and small intestinal biopsies demonstrated a flattened mucosa with subepithelial collagen deposition. Colonic biopsies also showed a thickened subepithelial collagen band as well as a striking lamina propria inflammatory cell infiltrate. Symptomatic remission was induced with a gluten/lactose-free diet, oral prednisone, and sulfasalazine and has been maintained with gluten restriction alone. Repeat biopsies after 2 months demonstrated restoration of normal small intestinal and colonic collagen bands; only a chronic inflammatory cell infiltrate (consistent with microscopic/lymphocytic colitis) persisted in colonic biopsies. We propose that, in this instance, collagenous enterocolitis represented a diffuse manifestation of gluten sensitivity.


Heterotopic pancreas diagnosed by endoscopic ultrasonography and endoscopic injection of ethanol to make a histologic diagnosis. A gastric submucosal tumor in a 56-year-old man was presumed to be heterotopic pancreas on the basis of endoscopy and endoscopic ultrasonography. To obtain a histologic diagnosis we injected ethanol at the tumor site to create an artificial ulcer. This facilitated the removal of endoscopic biopsy specimens from the submucosal layer so that histologic examination could confirm the presence of heterotopic pancreatic tissue.


Endoscopic removal of colonic leiomyoma. Most gastrointestinal leiomyomas are found in the stomach, only 3% of them arising in the colon. Surgical resection of the leiomyoma is usually necessary owing to its submucosal location. We describe a patient with a 1.5 cm pedunculated leiomyoma of the colon successfully removed by colonoscopic snare electrocauterization. We believe this to be the first report of a colonic leiomyoma of this size removed endoscopically without complication. We review the literature regarding gastrointestinal leiomyomas with special attention to pedunculated leiomyomas and their endoscopic management.


Pathogenesis of hepatic fibrosis and the role of cytokines. No definitive therapy exists for the treatment of hepatic fibrosis and cirrhosis. Recent evidence suggests that hepatic lipocytes (Ito cells, fat storage cells, or stellate cells of the liver) are responsible for much of the collagen hypersecretion and nodule formation that occurs during hepatic fibrosis and cirrhosis. This review describes the cellular mechanisms of hepatic fibrogenesis emphasizing new experimental data about cytokines or growth factors to suggest potential avenues of future therapeutic design.


Epidemiological study of peptic ulcer disease among Japanese and Koreans in Japan. Peptic ulcer among Japanese and Koreans in Japan has rarely been studied. In this 10-year study of hospital-based endoscopy, we focused on the epidemiology of peptic ulcer among these ethnic groups in Japan. Between 1980 and 1990, 81.2% of all patients examined via endoscopy at Saikyo Hospital in Kyoto completed a life-style questionnaire: 1,264 Japanese (70.5%), 503 Koreans (28.1%), and 25 persons of unknown ethnicity (1.4%). Characteristics of ulcer disease were almost identical for Koreans and Japanese. Like other world-wide patterns, the male to female ratio was 2.3:1. Unlike results from Western countries, however, the overall gastric ulcer rate was 1.5 times higher than for duodenal ulcer. This higher rate was due to the relatively high rate of gastric ulcer in the older age groups; among persons less than 40 years of age, duodenal ulcer was diagnosed more often than gastric ulcer. The mean age at diagnosis of duodenal ulcer (40.7 years) was significantly lower (p less than 0.005) than that for gastric ulcer (53.7 years). Multivariate-adjusted odds ratios were calculated using a multiple logistic regression model. Cigarette smoking significantly increased the risk for both gastric ulcer (odds ratio = 3.10, 95% confidence interval [CI] 2.1-4.6) and duodenal ulcer (odds ratio = 1.9, 95% CI 1.2-2.9). Age greater than or equal to 40 years (odds ratio = 2.3, 95% CI 1.6-3.3) and consumption of salty foods (odds ratio = 1.5, 95% CI 1.0-2.1) also significantly increased the risk for gastric ulcer.(ABSTRACT TRUNCATED AT 250 WORDS)


Spontaneous nonfistulous barium reflux into the biliary tract: association with duodenal ulcer disease. A report of four cases. Reflux of barium into the bile duct system during a barium study of the upper gastrointestinal tract is rare in the absence of spontaneous or postoperative fistula. We report four patients, three men and one woman, who had such reflux, associated with active duodenal ulcer disease, shown at radiologic and endoscopic investigation. Reflux of gastrointestinal contents into the biliary tract can result from peptic ulcer disease with duodenal involvement. The finding does not necessarily imply fistulous communication, ulcer perforation, or surgical emergency.


Does endoscopy improve prediction of the prognosis in upper gastrointestinal bleeding? To evaluate the prognostic value of the endoscopic examination, we included 189 consecutive patients with upper gastrointestinal bleeding, in a prospective study. Rebleeding was more frequent in patients with endoscopic stigmata of hemorrhage. The prognostic prediction given by the physician was slightly, but not significantly, improved after the result of the endoscopy was available. However, when the clinical data were evaluated by computer, using the Bayes' theorem, the endoscopic findings provided no additional prognostic value. We conclude that the endoscopic findings have intrinsic prognostic value, but add little to clinical data obtained on admission.


Nitric oxide production by monocytes in alcoholic liver disease. Nitric oxide, initially described as an endothelial-derived relaxing factor, has recently been recognised as a mediator of macrophage function. We have studied the production of nitric oxide by peripheral blood monocytes from both normal volunteers and alcoholics. This was measured indirectly by assessing nitrite formation. Normal monocytes were found to produce a basal level of nitrite, which could be stimulated more than 6-fold using endotoxin. This effect was abrogated by the addition of nitric oxide synthesis inhibitor, L-n-monomethyl-arginine. A striking difference was observed in the monocytes obtained from alcoholics with and without evidence of alcoholic hepatitis. Whereas the latter behaved in a similar manner to the controls, the former had markedly increased basal levels. In the hepatitis group there was also substantial inhibition of production by L-n-monomethyl-arginine. We believe that these results indicate that nitric oxide derived from monocytes may play a role in the pathogenesis of alcoholic liver disease, especially alcoholic hepatitis.


Reversible bile acid changes in bile duct obstruction and its potential for hepatocellular injury. The etiology of hepatocellular dysfunction resulting from chronic biliary obstruction is not clearly understood. Alterations in bile acid metabolism due to changes in microsomal cytochrome P-450 enzyme activities may have a fundamental role in cholestatic liver injury. This study examines the very early changes in both biliary bile acids and hepatic microsomal cytochrome P-450 content after bile duct obstruction in the rat and the effects of the restoration of bile flow after 3 days of biliary obstruction. We found that early induction of cytochrome P-450 may be a fundamental step in the generation of cholestatic liver injury mediated by hepatotoxic bile acids. The rapid reversal of bile acid changes with reconstituted bile flow indicate that the liver is able to quickly recover when obstruction is relieved. Characterization of this fundamental process may ultimately provide a means of modulation of cholestatic hepatotoxicity.


Caffeine clearance in cirrhosis. The value of simplified determinations of liver metabolic capacity. Less complex methods of measuring hepatic metabolic capacity are needed. A simplified caffeine clearance test was evaluated in 23 patients with stable alcoholic liver disease. First, saliva caffeine concentrations were measured over a 24-h caffeine-free interval. Clearance was calculated from the rate of elimination of caffeine and an assumed volume of distribution and compared with the results of a formal clearance test using sequential plasma and saliva samples following a 300 mg oral dose. The simplified method was then assessed in 11 hospitalized patients with cirrhosis. Saliva caffeine concentrations remained measurable over the interval of study in 82% of patients. Caffeine clearance as determined by the simplified method did not differ from plasma caffeine clearance after an oral dose. Application of this method was achieved in 11 of 12 patients hospitalized for complications of severe liver disease, and revealed markedly diminished clearance. Thus, caffeine clearance can be accurately estimated in patients with severe liver disease using two or more samples of either saliva or plasma. This simplified determination of caffeine elimination rate provides a more practical assessment of hepatic metabolic capacity than a formal clearance test.


Protein C in patients with alcoholic cirrhosis and other liver diseases. The coagulation inhibitor protein C was measured in 151 patients with various liver diseases. The protein C level was significantly decreased in patients with alcoholic cirrhosis (n = 73) compared to patients with steatosis (n = 24) (40 +/- 2%) vs. 88 +/- 4%, mean S.E., p less than 0.001). It was also decreased in cases of acute liver damage (n = 8) and in patients with non-alcoholic cirrhosis (n = 15) (35 +/- 7% and 36 +/- 4%, respectively). A significant correlation was found between protein C and Normotest, antithrombin, heparin cofactor II, (r = 0.83, r = 0.82, r = 0.81, respectively, p less than 0.001). There was also a significant correlation between protein C and serum concentrations of albumin (r = 0.61, p less than 0.001), but a negative association to bilirubin (r = -0.56). No significant association was found between protein C and aspartate aminotransferase, alaline aminotransferase, and gamma-glutamyltranspeptidase. In conclusion, protein C is low in advanced liver diseases and gives the same amount and type of information as Normotest, antithrombin and heparin cofactor II.


Course of hepatitis B and D virus infection in auxiliary liver grafts in hepatitis B-positive patients. A light-microscopic and immunohistochemical study. Four patients who received an auxiliary partial liver graft for decompensated liver cirrhosis due to hepatitis B (HBV), associated in two cases with hepatitis D virus (HDV) superinfection, were studied. The sequential appearance of hepatitis B and D antigens in the grafts was investigated in serial liver biopsies by immuno-histochemical methods and compared with the viral antigenic profiles of the host livers. The histological changes in the liver grafts were studied in relation to the viral expression patterns. One week after transplantation, expression of HBsAg was already apparent in two grafts. HBcAg was found in the graft of the only patient with HBcAg in the host liver. HDAg was expressed in the grafts of both patients with HDV superinfection; in one of these cases HDAg was present without HBsAg. At 3 months, viral antigen expression was maximal. Expression of HBsAg and HBcAg in the grafts of the two HDV-positive patients was, however, less extensive than in the two HBV-positive patients. All patients developed a mild lobular hepatitis, histologically demonstrated between the 47th and 107th posttransplantation day. In the two HBV-positive, HDV-negative patients, cirrhotic transformation of the graft occurred within 1 year. In the HDV-positive patients only a mild chronic active hepatitis with slight or moderate fibrosis was observed after 1 year. We conclude that recurrence of HBV and HDV infection in auxiliary liver grafts is demonstrable within 1-3 weeks. HBV infection in liver grafts may be a rapidly progressive disease. Coinfection with HDV does not aggravate the acute hepatitis and may even suppress the progression of chronic HBV.


Selenium in chronic liver disease.

Selenium in chronic liver disease. In order to assess the role of selenium (Se) in chronic liver disease, we have measured serum, urinary and hepatic selenium in a range of liver diseases and correlated them with nutritional status and conventional liver biochemistry. Serum Se levels (microgram/l +/- S.D.) were significantly lower in both alcoholic (63.6 +/- 18.2, p less than 0.0001) and non-alcoholic liver disease (NALD) (60.6 +/- 13.6, p less than 0.0001) compared to healthy controls (87.8 +/- 21.2) and non-malignant 'disease controls' (80.3 +/- 19.1). Hepatic Se levels (microgram/g of dry weight) were also reduced in both ALD (0.568 +/- 0.647, p less than 0.005) and NALD (0.863 +/- 0.308, p less than 0.005) compared to controls (1.227 +/- 0.296), 24-h urinary Se excretion (microgram) in ALD (24.6 +/- 10.7) and NALD (29.0 +/- 14.3) was similar to controls (30.3 +/- 8.7). Serum Se showed a highly significant positive correlation with albumin (p less than 0.001) in both ALD and NALD. Serum levels were also significantly correlated with anthropometric measurements. Dietary assessment of patients with primary biliary cirrhosis and low serum Se levels did not show a reduced dietary intake. Our data show that Se levels are low in liver disease irrespective of aetiology and suggest that these low levels are more likely to be related to overall nutritional status than to dietary intake.


Fasting gallbladder volume, postprandial emptying and cholecystokinin release in gallstone patients and normal subjects. Since abnormal gallbladder emptying may be a contributing factor in the development of gallstone disease, we determined fasting gallbladder volume and postprandial contraction in 20 gallstone patients and 20 normal subjects with the aid of ultrasonography. Moreover, basal plasma cholecystokinin levels and postprandial cholecystokinin (CCK) release were determined. Gallstone patients were divided into strong contractors (13 pts) and weak contractors (below 95% confidence interval for AUC contraction in % during 90 min: 7 pts). Strong contractor patients had significantly larger mean fasting volumes than normal subjects (mean +/- S.E.: 34.9 +/- 6.1 ml and 18.9 +/- 1.6 ml, respectively). This was not true for weak contractor patients (mean fasting volume 23.2 +/- 3.2 ml). Both strong contractor and weak contractor patients had significantly higher mean residual volumes than normal subjects (17.0 +/- 4.1 ml, 18.0 +/- 2.9 ml, and 8.8 +/- 1.1 ml, respectively). Absolute gallbladder emptying was significantly higher for strong contractor patients than for normal subjects, but relative emptying was the same. Opposite patterns of CCK release occurred in gallstone patients and normal subjects. In normal subjects, more CCK release was associated with stronger gallbladder emptying. In contrast, weak contractor gallstone patients had significantly higher CCK release than strong contractor patients. (AUC CCK: 304 +/- 89 pmol/l x 90 min and 106 +/- 29 pmol/l x 90 min, respectively). The present study indicates that strong contractor gallstone patients may have large residual gallbladder volumes due to large starting volumes, whereas weak contractor patients may have large residual volumes due to impaired contraction. Subjects with large fasting and residual volumes may be at increased risk for gallstone disease.(ABSTRACT TRUNCATED AT 250 WORDS)


Polycystic hydatid disease (Echinococcus vogeli). Clinical, laboratory and morphological findings in nine Brazilian patients. Polycystic hydatid disease occurs in neotropical zones and is caused by Echinococcus vogeli. The paca, a wild rodent, is the intermediate host and the final host is the dog. Seven cases of polycystic hydatid disease autochthonous to the Brazilian Amazon region are described. The disease was polycystic in all cases and diagnosis was based on anatomopathological findings. E. vogeli was identified by the shape and dimensions of the rostellar hooks. The liver was the organ most often involved (6/7), followed by the lungs (2/7) and mesentery (2/7), spleen (1/7) and pancreas (1/7). The main clinical manifestations were abdominal pain, hepatomegaly, jaundice, weight loss, anemia, fever, hemoptysis, palpable abdominal masses and signs of portal hypertension. Hepatic calcifications were detected in four cases. Two cases from the hinterland of the State of São Paulo are also reported. Both had calcified round structures in the liver, highly suggestive of calcified polycystic hydatids. The aim of the present report was to report on this relatively unknown hydatid disorder of Tropical America and to disseminate its clinical, ultrasound and radiological features.


Phenotypical modulation of liver fat-storing cells by retinoids. Influence on unstimulated and growth factor-induced cell proliferation. In conditions of chronic liver inflammation, liver fat-storing cells (FSC) differentiate into 'myofibroblast-like cells'. This transition is characterized by a gradual loss of vitamin A stores, and previous studies suggest a possible relationship between the intracellular retinoid content and the proliferative potential of this cell type. In the present study, we further characterized this aspect of FSC biology by monitoring ultrastructural changes and growth characteristics during several serial passages in culture. Our observations suggest that the complete transition to the 'myofibroblast-like phenotype' is paralleled by a sudden and remarkable increase in the growth rate. At this stage, cell growth appears rather independent from the presence of mitogens in the culture medium, suggesting cell transformation. Accordingly, the mitogenic effects of platelet-derived growth factor and epidermal growth factor appears reduced when compared to those observed in FSC retaining the original 'storing' phenotype. Incubation of vitamin A-depleted FSC with retinol and retinoic acid resulted in the partial recovery of intracellular retinoid stores and in a significant reduction of basal growth rate and basal and growth factor-induced DNA synthesis. In summary, these in vitro observations suggest that intracellular retinoids play a central role in the control of unstimulated and growth factor-induced FSC proliferation and may help understand in vivo mechanisms leading to liver fibrosis.


Anti-HBe-positive chronic hepatitis B with HBV-DNA in the serum response to a 6-month course of lymphoblastoid interferon. Eighteen heterosexual HBsAg carriers with anti-HBe- and HBV-DNA-positive chronic hepatitis B (CHB) were randomly assigned to receive human lymphoblastoid interferon (ly-IFN) at a dose of 5 MU/m2 i.m. three times a week for 6 months (ten cases) or no treatment (eight cases). All patients were followed for 24 months after IFN discontinuation and received a second liver biopsy. During the 6 months of treatment all patients had a progressive reduction of serum HBV-DNA levels, and at the end of therapy nine out of ten were HBV-DNA-negative and had normal ALT values. None of the untreated patients became persistently HBV-DNA-negative or showed significant variations of ALT levels. During the post-treatment follow-up, from 1 to 17 months after ly-IFN discontinuation, eight of the nine responders (89%) had recurrent or persistent reappearance of HBV-DNA in the serum and reactivation of the liver disease activity, with an ALT peak in four of them. On the post-trial liver biopsy seven of the eight relapsed patients showed persistence of HBcAg reactivity with no significant difference in the percentage of positive cells with respect to the pre-treatment liver specimen. Histological features improved in four treated patients, worsened in one untreated case and were unchanged in the remaining patients. These results indicate that ly-IFN shows a transient antiviral effect in the therapy of anti-HBe- and HBV-DNA-positive CHB. The 6-month treatment regimen employed in this study seems insufficient for eradicating the replicating virus from the liver cells in the majority of patients and consequently does not appear to prevent HBV reactivation after IFN discontinuation.


Effects of an increase in protein intake on hepatic efficacy for urea synthesis in healthy subjects and in patients with cirrhosis. The efficacy of urea synthesis as measured by functional hepatic nitrogen clearance (i.e., the relation of urea synthesis rate to blood alpha-amino nitrogen concentration) was studied before and after diet protein supplementation in six healthy subjects and five patients with stable cirrhosis (galactose elimination capacity about 60% of control). Daily protein intake was increased for 14 days by a protein-enriched liquid from (mean +/- S.D.) 1.01 +/- 0.32 g/kg body wt. to 1.62 +/- 0.31 g/kg body wt in the control subjects, and from 0.69 +/- 0.21 g/kg body wt. to 1.50 +/- 0.15 g/kg body wt. in the patients with cirrhosis. This increased the hepatic nitrogen clearance from 27 +/- 10 l/h to 39 +/- 15 l/h in the control subjects (p less than 0.05) and from 15 +/- 6 l/h to 21 +/- 7 l/h in the cirrhosis patients (p less than 0.05). There was no effect on the galactose elimination capacity in any group. Compared to the control subjects, the response in hepatic nitrogen clearance relative to the increase in protein intake was reduced by 60% in the patients. Basal glucagon was 75% higher in the patients and increased by 50% during high protein intake (p less than 0.05), but did not parallel the increase in hepatic nitrogen clearance, and it did not change in the control subjects. The study shows that an increase in protein intake selectively increases liver function with regard to disposal of amino nitrogen; the mechanism is qualitatively intact but quantitatively deficient in patients with cirrhosis of the liver, and does not seem to depend on glucagon.


Pathophysiology of elevated ascites fluid cholesterol in malignant ascites. Increased ascites to serum relation of proteins and lipoproteins in patients with peritoneal carcinomatosis as compared to patients with cirrhosis of the liver. The existence of marked elevations of ascitic fluid cholesterol has been observed in patients with peritoneal carcinomatosis compared to patients with cirrhosis and has been found useful in differential diagnosis. This finding could be caused by an enhanced movement of plasma lipoproteins into the peritoneal cavity. To test this hypothesis we determined the fasting concentrations of total, high density lipoprotein (HDL)- and low density lipoprotein (LDL)-cholesterol, apolipoprotein-A1 (apo-A1) and apolipoprotein-B (apo-B) in serum and ascites of 17 patients with cirrhosis and 16 patients with peritoneal carcinomatosis. The movement of proteins from plasma to ascites was calculated from the ascites/serum concentration ratios of six different sized proteins with a molecular mass ranging from 54 kDa to 971 kDa. Mean values (mg/dl) for total cholesterol (92.6 vs. 21.0), HDL-cholesterol (15.6 vs. 1.8), LDL-cholesterol (63.4 vs. 16.1), apo-A1 (50.2 vs. 13.6) and apo-B (41.2 vs. 12.9) in ascites were significantly higher in peritoneal carcinomatosis than in cirrhosis. These differences could only partially be explained by the higher serum concentrations of these parameters in peritoneal carcinomatosis, but were mainly due to a lower selectivity for the movement of plasma proteins and lipoproteins into ascites (mean ascites/serum (A/S) ratio: 0.30-0.77) in peritoneal carcinomatosis as compared to cirrhosis (mean ascites/serum ratio: 0.11-0.21). In both groups about 85% of the total cholesterol in serum and ascites consisted of HDL- and LDL-cholesterol. These findings support the hypothesis that elevations in ascitic cholesterol in peritoneal carcinomatosis compared to cirrhosis are mainly caused by the increased movement of plasma HDL and LDL into the peritoneal cavity.


Diuresis increases ascitic fluid opsonic activity in patients who survive spontaneous bacterial peritonitis. Patients with low protein ascites and deficient ascitic fluid opsonic activity have been shown to be unusually predisposed to development of spontaneous bacterial peritonitis. Survivors of spontaneous peritonitis frequently develop recurrent infection. Diuresis has been shown to increase the ascitic fluid opsonic activity of patients who have never had spontaneous bacterial peritonitis. Patients with adequate opsonic activity are protected from ascitic fluid infection. Theoretically, the subset of patients who develop spontaneous peritonitis may have such severe liver disease that (i) their ascites is refractory to diuretic therapy or (ii) their ascitic fluid opsonic activity does not increase in response to diuresis. In this study, opsonic activity and concentrations of total protein and complement components were measured in the ascitic fluid of 11 patients who were hospitalized with spontaneous bacterial peritonitis and who responded to oral diuretics. The mean values of all of these parameters were found to increase significantly comparing the end-of-diuresis samples to the specimens that were diagnostic of ascitic fluid infection. Patients who survive spontaneous bacterial peritonitis are able to increase their ascitic fluid total protein and opsonic activity in response to diuresis. This increase in endogenous antimicrobial activity may help prevent recurrence of ascitic fluid infection.


Hepatic oxidant and antioxidant systems in portacaval-shunted rats. The purpose of the present study was to determine the effects of chronic portal diversion on antioxidant levels in the rat liver. Male Sprague-Dawley rats (n = 32) were used for these studies. An end-to-side portacaval anastomosis was constructed in 17 of the rats. Sham-operated rats (n = 15) served as controls. Two weeks later, hepatic blood flow was measured by the radioactive microsphere technique and the liver was harvested for biochemical measurement of catalase, manganese superoxide dismutase, copper-zinc superoxide dismutase, selenium glutathione peroxidase, xanthine oxidase, xanthine dehydrogenase and reduced glutathione (acid soluble sulfhydryls). Total hepatic blood flow was approx. 40% lower in portacaval-shunted rats when compared to sham-operated control rats. Total superoxide dismutase (SOD) and xanthine dehydrogenase (XD) levels were significantly reduced in the liver of shunted rats when compared to controls. Xanthine oxidase activity was unaltered. The decreased superoxide dismutase levels were exclusively due to reductions in the cytosolic Ca/Zn SOD; Mn SOD levels were unaltered. These data are consistent with oxidant stress and suggest that the liver of subjects with conditions characterized by decreased portal blood flow may be more susceptible to oxidant-induced liver injury.


Aprindine-induced hepatic granulomata.

Aprindine-induced hepatic granulomata. Aprindine is a very effective antiarrhythmic agent with a narrow therapeutic ratio. We report a patient who suffered from granulomatous hepatitis probably due to the administration of aprindine. Evidence of hepatitis appeared within 6 weeks of initiating aprindine therapy and resolved rapidly when the drug was withdrawn. Six months later, fibrosis but no granulomata were found in the expanded portal tracts. Our observations suggest that granulomatous hepatitis can occur during aprindine therapy.