Showing papers by "Oregon Health & Science University published in 1985"

Reduction of Plasma Lipids, Lipoproteins, and Apoproteins by Dietary Fish Oils in Patients with Hypertriglyceridemia

Abstract: Dietary fish oils, which are rich in omega-3 fatty acids, have been reported to reduce plasma lipid levels in normolipidemic subjects. We examined the effects of fish oil in 20 hypertriglyceridemic patients: 10 with Type IIb hyperlipidemia and 10 with Type V. These patients were put on three diets differing primarily in fatty acid composition and fat content. The control diet contained a fatty acid mixture typical of a low-fat therapeutic diet (ratio of polyunsaturated to saturated fat, 1.4), the fish-oil diet contained omega-3 fatty acids, and the vegetable-oil diet was rich in the omega-6 fatty acid, linoleic acid. Each diet was followed for four weeks. In the Type IIb group, the fish-oil diet led to decreases in both plasma cholesterol (-27 per cent) and triglyceride (-64 per cent), as compared with the control diet. Very-low-density lipoproteins (VLDLs) were also reduced markedly. The vegetable-oil diet had much less effect. With fish oil, the Type V group had marked decreases in total cholesterol and triglyceride levels (-45 and -79 per cent, respectively). VLDL levels were dramatically lowered, as were apoprotein E levels. The vegetable-oil diet (unlike the fish-oil diet) produced a rapid and significant rise in plasma triglyceride levels. We conclude that fish oils and fish may be useful components of diets for the treatment of hypertriglyceridemia.

Distribution and regulation of aromatase activity in the rat hypothalamus and limbic system.

Abstract: Conversion of androgen to estrogen in the rat brain is catalyzed by aromatase enzymes. The maximum concentrations of these enzymes are found within the hypothalamus and amygdala, where they appear to play an important role in the process by which androgens affect both behavior and neuroendocrine function. In the present study, we measured the levels of aromatase activity (AA) in 20 nuclei and brain regions of the adult rat brain. Individual nuclei were microdissected from 600-micron frozen sections. Tissues from 3 animals were pooled, and AA was measured by an in vitro radiometric assay that quantifies the stereospecific production of 3H2O from [1 beta-3H]androstenedione as an index of estrogen formation. We report that AA is heterogeneously distributed within the rat brain. The greatest amounts of activity were found in the bed nucleus (n.) of the stria terminalis (700 protein fmol/h . mg) and in the medial (MA) and cortical amygdala (400-600 fmol/h . mg protein) of the male. There was an evident rostral-caudal and medial-lateral gradient in AA throughout the diencephalon. Activity was high in the periventricular preoptic n. and medial preoptic n.; intermediate in the suprachiasmatic preoptic n., anterior hypothalamus, periventricular anterior hypothalamus, and ventromedial n.; and low in the arcuate n.-median eminence, lateral preoptic n., supraoptic n., dorsomedial n., and lateral hypothalamus. Regions devoid of measurable AA included the medial and lateral septum, caudate-putamen, hippocampus, and parietal cortex. In the female, AA was greatest in the MA and cortical amygdala. We found that AA in the MA, stria terminalis n., suprachiasmatic preoptic n., periventricular preoptic in., medial preoptic n., anterior hypothalamus, and ventromedial n. was significantly greater (P less than 0.05) in males than in females. Orchidectomy reduced AA to levels seen in females, and administration of testosterone to castrated males restored AA in these areas. No significant sex differences were observed in any other hypothalamic or amygdaloid nuclei, although AA was increased by testosterone treatment in the periventricular anterior hypothalamus, arcuate n.-median eminence, and lateral hypothalamus. Our results provide a quantitative profile of AA in specific hypothalamic and limbic nuclei of the rat brain as well as information on the control of AA within these discrete regions.

Current concepts. Wernicke's encephalopathy.

Abstract: Despite its description over a century ago, Wernicke's encephalopathy continues to be underrecognized in both alcoholic and nonalcoholic populations. Recent studies suggest that Wernicke's encephal...

Preventable trauma deaths. A review of trauma care systems development.

Abstract: ACCIDENTAL death, characterized as the neglected disease of modern society, 1 is the leading mortality cause for persons 1 through 39 years of age and the third for those of all ages. 2 Because of the medical, social, and economic implications of trauma, attention is increasingly focusing on a systems approach to reducing traumatic death and disability through prevention, treatment, and research. 3-5 Regional trauma care systems have not been universally implemented, however, because of concerns about need, efficacy, and cost. This review traces the evolution of the preventable death concept, discusses its influence on trauma care systems development, and proposes future research directions. HISTORICAL REVIEW The American College of Surgeons first addressed trauma care in 1922 by forming the Committee on Treatment of Fractures, now the Committee on Trauma. 6 Excepting the military experience, 7 however, care quality for the multiply injured received relatively little attention during the next

DNA binding to human leukocytes. Evidence for a receptor-mediated association, internalization, and degradation of DNA.

Abstract: Previous studies have indicated that white blood cells possess DNA on their outer membranes. In this study we set out to determine whether exogenous DNA bound to cells in a fashion compatible with a ligand receptor union. Purified populations of white blood cells; neutrophils (polymorphonuclear leukocytes, PMN), adherent mononuclear cells (ADMC), rosetting lymphocytes (E+ cells), and nonrosetting lymphocytes (E- cells) were incubated with radiolabeled lambda phage DNA in increasing concentrations. Binding of [3H]DNA was a saturable process and was inhibited by excess cold DNA and prior trypsinization of the cells. Rate zonal density centrifugation of purified cell membrane preparations confirmed that DNA was binding to the outer cell surface. The dissociation constant for all four cell types was approximately 10(-9) M, and from 0.81 X 10(3) to 2.6 X 10(3) molecules of lambda phage DNA bound to each cell depending upon cell type. Binding was not competitively inhibited by RNA, polydeoxyadenylic acid-polydeoxythymidylic acid (poly [d(A).d(T)]), or mononucleotides. Sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE)-separated proteins from PMN, ADMC, E+, and E- cells were electrophoretically blotted onto nitrocellulose sheets; a probe of biotin-labeled DNA indicated a single species of DNA-binding molecule migrating in a position consistent with a molecular weight of 30,000. Isotopic and immunofluorescent studies indicate that DNA is internalized and degraded to oligonucleotides; this process is inhibited by cycloheximide. These results support the notion that there is a common binding site for DNA on white blood cells, that the stoichiometry of the association is compatible with a ligand receptor relationship, and that this apparent receptor is responsible for the endocytosis and degradation of exogenous DNA.

Supersensitivity to light: possible trait marker for manic-depressive illness.

Abstract: Exposure to light during the night reduces plasma melatonin levels. A previous study showed that, in response to light, nighttime plasma melatonin levels fell twice as much in a group of acutely ill manic-depressive patients as in a group of normal subjects. The present study compares 11 euthymic manic-depressive patients not taking medications with 24 age- and sex-matched normal subjects. Melatonin levels in these patients also fell twice as much as the levels of the normal subjects, suggesting that supersensitivity to light may be a trait marker for bipolar affective disorder.

Blood Pressure Response to Oral Calcium in Persons with Mild to Moderate Hypertension: A Randomized, Double-Blind, Placebo-Controlled, Crossover Trial

Abstract: The blood pressure response of 48 hypertensive persons and 32 normotensive persons to elemental calcium (as the carbonate or citrate salt), 1000 mg/d for 8 weeks, was assessed in a randomized, double-blind, placebo-controlled, crossover trial Compared with placebo, Ca2+ significantly lowered supine systolic blood pressure by 38 mm Hg, standing systolic blood pressure by 56 mm Hg (p less than 002), and supine diastolic blood pressure by 23 mm Hg (p less than 005) in hypertensive persons The response in normotensive persons differed significantly from that in hypertensives (p less than 003) as their blood pressure was unchanged Twenty-one (44%) hypertensive and 6 (19%) normotensive persons achieved a reduction in standing systolic arterial pressure of 10 mm Hg or greater Reported adverse effects were similar between calcium and placebo phases and did not necessitate withdrawal of any patient from the trial Treatment with 1000 mg/d of oral Ca2+ for 8 weeks represents a safe, well-tolerated, nonpharmacologic intervention that lowers blood pressure in selected patients with mild to moderate hypertension

In vivo gonadotropin-releasing hormone release and serum luteinizing hormone measurements in ovariectomized, estrogen-treated rhesus macaques.

Abstract: The push-pull perfusion technique was used to measure GnRH release in unanesthetized female rhesus macaques (Macaco mulatto) and to examine the dynamic relationship between GnRH release and LH levels during the estrogeninduced LH surge. Each ovariectomized macaque was anesthetized and stereotaxically fitted with a push-pull cannula directed into the median eminence (ME). After at least 1 week of recovery, each animal received an estradiol benzoate (E2B) injection (42 μg/kg BW) or an oil (OIL) injection and underwent pushpull perfusion of the ME and blood sampling for at least 5 h between 28 and 56 h postinjection. Continuous 10-min pushpull perfusates were collected and prepared for GnRH RIA. Peripheral venous blood samples were obtained either hourly or every 10 min, and serum LH levels were determined by Leydig cell bioassay. GnRH release was detectable and pulsatile in areas in or adjacent to the ME or arcuate nucleus. In eight OIL monkeys, GnRH pulses were regular (∼one pulse every 60 min) and of low ...

Health care episodes: definition, measurement and use.

Abstract: *Senior Investigator, Kaiser Permanente Center for Health Research, Portland, Ore.; Associate Professor, Department of Community Health Care Systems, School of Nursing, The Oregon Health Sciences University, Portland. †Internist, Northwest Permanente, P.C., Physicians and Surgeons, Portland, Ore.; Adjunct Senior Investigator, Kaiser Permanente Center for Health Research, Portland; Clinical Associate Professor of Medicine, School of Medicine, The Oregon Health Sciences University, Portland. ‡Senior Investigator, Kaiser Permanente Center for Health Research, Portland, Ore. Health care differs from other commodities because it is

A double blind crossover trial of prednisone versus placebo in the treatment of fibrositis.

Abstract: Twenty patients with a diagnosis of fibrositis were entered into a double blinded crossover study to compare the effects of prednisone versus placebo. Each patient was randomly assigned to either prednisone 15 mg/day or placebo for 14 days of therapy and then therapy was switched for a further 14 days. The following measurements were assessed at baseline, end of Week 2 and end of Week 4: analogue scores for pain, sleep disturbance, morning stiffness and fatiguability, and dolorimetry readings of pain tolerance over 14 representative tender points. Overall there was no improvement while taking prednisone, indeed most measured variables showed a trend towards deterioration with this therapy.

The effect of carbidopa on the pharmacokinetics of intravenously administered levodopa: the mechanism of action in the treatment of parkinsonism.

Abstract: The pharmacokinetics of short and long intravenous infusions of levodopa with and without concurrent oral administration of carbidopa was studied in 9 parkinsonian patients. Carbidopa reduced by 50% both the infusion rate required to produce a clinical response and the time required for plasma clearance of levodopa. Using this value for clearance, it is estimated that carbidopa doubles the bioavailability of orally administered levodopa. Carbidopa did not alter the therapeutically effective plasma concentration of levodopa, suggesting that carbidopa does not modify the so-called enzymatic blood-brain barrier. The decline of the plasma levodopa concentration was biphasic; carbidopa modestly increased half-lives of both phases. The apparent volume of distribution was not significantly altered. Carbidopa did not change the duration of the clinical response after the discontinuation of short infusions. From these observations we infer that the therapeutic effects of carbidopa can be attributed to doubling the bioavailability of orally administered levodopa and halving its plasma clearance.

Xanthomas and hyperlipidemias

Abstract: The ability to recognize diverse clinical forms of xanthomas, such as tuberous, planar, eruptive and tendinous, is important in the detection of underlying systemic disease. A variety of primary genetic disorders, as well as numerous secondary conditions such as diabetes, obstructive liver disease, thyroid disease, renal disease, and pancreatitis, can lead to hyperlipoproteinemia that results in the formation not only of xanthomas but also of life-threatening vascular atherosclerosis. An understanding of the pathogenesis of the underlying lipoprotein alterations provides a rational approach to therapy utilizing dietary manipulations and drugs. Such treatment is capable of correcting most disorders of lipid metabolism, and, if appropriate therapy is initiated at the first sign of xanthoma evolution, it may prevent progression of atherosclerosis, provide resolution of xanthomas, and in some instances prevent serious pancreatitis.

Effects of pH, lactate, and viscoelastic drag on sperm motility: a species comparison.

Abstract: Little or no motility is observed when sperm from 5 mammalian species are incubated in vitro in their cauda epididymal fluid (CEF). We examined the effects of pH, lactate, and viscoelastic drag on sperm motility to determine whether these factors are responsible for this inhibition of motility. The pHs of CEF from bull, dog, rat, guinea pig, and hamster were 5.8, 6.2, 6.9, 6.9, and 7.2, respectively. The lactate concentration of epididymal semen collected from anesthetized animals ranged from 0.6 to 0.9, but increased almost 10-fold in samples from rats or dogs when measured 2 h postmortem. Increasing the pH of CEF to 7.0 resulted in the initiation of full motility for bull and dog sperm. Suspensions of sperm in buffer at various pHs (from 4.0 to 7.6) produced a sigmoidal motility curve for all species. All species, including bull and dog, showed almost full motility in buffer at a pH equal to the pH of their own CEF. Motility of bull and dog sperm showed greater inhibition with decreasing pH when suspended in CEF instead of buffer. The addition of 15 mM lactate, which has been shown to lower sperm intracellular pH, shifted the motility versus pH curves of all species toward higher pH. In bull and dog the addition of lactate produced a motility profile that was indistinguishable from that in their own CEF. The viscoelastic drag of the CEF of only two species, rat and hamster, was sufficiently high to inhibit sperm motility. We conclude that the low pH of the CEF from bulls and dogs plus the presence of lactate is sufficient to cause inhibition of motility.(ABSTRACT TRUNCATED AT 250 WORDS)

Bidirectional selection for susceptibility to ethanol withdrawal seizures in Mus musculus.

Abstract: Using within-family selection from a genetically heterogeneous population of HS/Ibg mice, lines and replicates have been selected for high (withdrawal seizure prone; WSP) and low (withdrawal seizure resistant; WSR) susceptibility to convulsions after withdrawal from chronic exposure to ethanol. Two nonselected control lines (withdrawal-seizure control; WSC) have also been maintained. The response was bidirectional in both replicates across 11 selected generations, WSP and WSR lines differing approximately 10-fold in seizure severity after an identical regimen of chronic exposure to ethanol. Realized heritability was found to be approximately 0.28. The phenotype appears to be polygenic in nature. The relatively low amount of inbreeding in these lines and the large response to selection should make them useful for examining the physiological basis of physical dependence on ethanol.

Enhanced in vivo platelet activation in subtypes of ischemic stroke.

Abstract: It remains uncertain whether platelet activation in ischemic stroke is contributory or secondary to brain ischemia. The efficacy of aspirin (ASA) in stroke prevention suggests that platelet activation contributes to the occurrence of stroke. On the other hand, platelet activation may be simply a generalized consequence of cerebral ischemic damage. To examine this issue, plasma levels of the platelet specific proteins beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) were measured in fifty-eight patients with various defined types of acute ischemic strokes. beta-TG was a broader indicator of platelet activation than PF4. Compared with an age-matched control group, thromboembolic and cardioembolic stroke patients had significantly elevated beta-TG levels (p less than 0.001). Also, beta-TG levels in these stroke categories were significantly higher in samples drawn within the first week after the event than in those drawn later (p less than 0.001). In contrast, beta-TG levels in lacunar stroke patients and in most TIA patients were normal. beta-TG levels did not correlate with the volume of cerebral infarction as measured by planimetry from CT scans. Moreover, beta-TG levels in patients on chronic ASA therapy at the time of stroke did not differ from those in patients of the same diagnostic categories not taking aspirin. These data indicate that platelet activation may be important in some, but not all, subtypes of ischemic stroke and that platelet activation can occur in stroke even though the platelet cyclooxygenase pathway is suppressed.

Immediate and delayed effects of bright light on human melatonin production: shifting "dawn" and "dusk" shifts the dim light melatonin onset (DLMO)

Abstract: Since the discovery that bright light exposure suppresses nighttime melatonin production in humans,’ scientists have begun to ask the question: How can bright light be used to manipulate human circadian and seasonal rhythms? Understandably, clinicians have also become interested in the potential uses of bright light in the treatment of chronobiologic sleep and mood disorders. Drawing upon different types of animal studies, investigators have suggested alternative ways in which to use bright light exposure. For instance, Kripke and coworkers,’.’ reasoning from photoperiodic studies of seasonal reproductive behavior in hamsters and from the “critical interval” theory of Wehr and Wirz-Justice4 for sleep deprivation and depression, have suggested the use of bright light exposure in the morning for the treatment of major depression, a disorder thought to be associated with “fast” or phase advanced circadian rhythm^.^' On the other hand, we have drawn upon a different set of studies for understanding how to use bright light exposure to treat major (endogenous) depression: studies8-’’ of phase response curves (PRCs). These types of experiments are accomplished by exposing an animal “free-running” in constant dark to a short pulse of light and then recording the change in the timing of its activity-rest cycle. In both diurnal and nocturnal species, certain features of PRCs appear to be universal. When the pulse of light occurs during the animal’s subjective day (based on the activity-rest cycle), hardly any effect is noted. When the pulse of light occurs during the beginning of the animal’s subjective night, the animal will delay the phase position of its subsequent activity-rest cycles. When the pulse of light occurs during the end of the animal’s subjective night, the animal will advance the phase position of its subsequent activity-rest cycles. Based on the apparent universal nature of the PRC, we reasoned that humans, even though entrained, might respond in similar ways to bright light exposure.” We hypothesized that circadian phase position would be delayed by exposure to bright light in the evening and advanced by exposure to bright light in the morning. (We

One-year follow-up study of posttraumatic stress disorder among survivors of Cambodian concentration camps.

Abstract: One year after receiving a diagnosis of posttraumatic stress disorder, five of 12 Cambodian concentration camp survivors who entered a treatment program no longer met the diagnostic criteria for the disorder, and symptoms in three others had improved. The intrusive symptoms of nightmares, sleep disorders, and startle reactions showed the most consistent improvement. Avoidance behavior, shame, and caring for others improved the least. The authors advocate use of tricyclic antidepressant medication and a consistent, supportive long-term psychotherapeutic commitment in treating this severely traumatized group.

Characterization of a new model of GM2-gangliosidosis (Sandhoff's disease) in Korat cats.

Abstract: We have detected a disorder in Korat cats (initially imported from Thailand) that is analogous to human Sandhoff's disease. Pedigree analysis indicates that this disease in an autosomal recessive disorder in the American Korat. Postmortem studies on one affected cat showed hepatomegaly that was not reported in the only other known feline model of GM2-gangliosidosis type II. Histologic and ultra-structural evaluation revealed typical storage vacuoles. There was a marked deficiency in the activity of hexosaminidase (HEX) A and B in affected brain and liver as compared to controls. Electrophoresis of a liver extract revealed a deficiency of normal HEX A and B in the affected animals. The blocking primary enzyme immunoassay verified the presence of antigenically reactive HEX present in affected cat livers in quantities slightly elevated with respect to the normal HEX concentration in control cats. In leukocytes, obligate heterozygotes had intermediate levels of total HEX activity with a slight increase in the percent activity due to HEX A. Indeed, 4 of 11 phenotypically normal animals in addition to four obligate heterozygotes appear to be carriers using this assay. Affected brain and liver compared with control brain and liver contained a great excess of bound N-acetylneuraminic acid in the Folch upper-phase solids; thin-layer chromatography showed a marked increase in GM2-ganglioside. In summary, we have characterized the pedigree, pathology, and biochemistry of a new feline model of GM2-gangliosidosis which is similar to but different from the only other known feline model.

Clinical characteristics of fibrositis. II. A "blinded," controlled study using standard psychological tests.

Abstract: Twenty-two patients with fibrositis and 22 control patients selected from a general medical outpatient population were given 3 standardized psychological questionnaires: the Beck Depression Inventory, the Spielberger State and Trait Anxiety Inventory, and the SCL-90-R. There were no statistically significant differences between fibrositis patients and control patients on any of these tests, a finding at variance with a commonly held belief that patients with fibrositis have an underlying psychological disorder. While psychological factors may be important in some patients with fibrositis, these results indicate that the presence of a psychopathologic condition is not mandatory for the persistence of fibrositis.

Pet-Associated Illness

Abstract: AN estimated 55 million dogs and nearly as many cats are kept as pets in the United States1 Although over 30 human illnesses can be acquired from pets,2 owners are often poorly informed about measures that prevent acquisition of these conditions3 Despite the frequency of contact between pet and owner, most pet-associated illnesses are infrequent, and health care providers may not be aware of their patterns of transmission or of preventive measures The topic of pathogens that are transmitted from animals to human beings (zoonoses) has received brief editorial attention recently4 , 5 In this article, we review in more detail the