Neuroendocrinology of acute immunity.

Bacterial endotoxins such as Escherichia coli lipopolysaccharide (LPS) bind to specific Toll-like receptors in fixed and circulating immunocompetent cells and activate the sympathetic and pituitary-adrenal system through similar receptors in cells that form the blood-brain interface. The latter, in turn, lead to the formation, within the brain, of proinflammatory cytokines including interleukin (IL)-1alpha, IL-1beta, IL-6, tumor necrosis factor alpha (TNF-alpha), and one or more antinflammatory cytokines including tumor growth factor beta (TGF-beta), and IL-10. Although the full panoply of central cytokines can be activated after systemic exposure, direct introduction of IL-1beta into the brain exerts a unique pattern of peripheral immune responses attributable to the special properties of reactive cells within the brain and to the "reservoir" function of the cerebrospinal fluid compartment.

Initial clinical evaluation of cardiac systolic murmurs in the ED by noncardiologists.

It is not exactly known how ED physicians perform in evaluating cardiac systolic murmurs. In 203 consecutive medical ED patients with systolic murmur, we compared the initial clinical evaluation, including auscultation, with transthoracic echocardiography. Of the 203 patients, 132 (65%) had innocent murmurs and 71 patients (35%) had valvular heart disease.

Cachexia in rheumatoid arthritis is not explained by decreased growth hormone secretion.

Objective: Patients with rheumatoid arthritis (RA) lose body cell mass (BCM) by unknown mechanisms. Since the loss of BCM in normal aging individuals parallels the characteristic age-related decline in growth hormone (GH) secretion, this study was carried out to determine whether further decreased GH secretion plays a role in the pathogenesis of this loss of BCM in RA patients, termed "rheumatoid cachexia."

Methods: GH secretory kinetics were determined by deconvolution analysis in 16 patients with RA and 17 healthy controls matched for age (mean +/- SD 45.

Parathyroid hormone-related protein (PTHrP) induction in reactive astrocytes following brain injury: a possible mediator of CNS inflammation.

PTHrP, a peptide induced in parenchymal organs during endotoxemia and in the synovium in rheumatoid arthritis, has recently been shown to be expressed in immature or transformed human astrocytes, but not in normal cells. This finding has led us to postulate that PTHrP might also be induced in reactive astrocytes in inflamed brain and, thus, act as a mediator of CNS inflammation. To test this hypothesis, PTHrP expression was examined following cortical stab wound injury in rats, a classical model of reactive gliosis.

Community-acquired pneumonia--which patients are hospitalised?

Background And Objective: Patients with community-acquired pneumonia can be allocated into low and high-risk mortality groups by simple clinical criteria. We studied the value of the stratification for outcome as proposed by Fine, et al. to guide the decision for in-hospital versus outpatient treatment in the emergency department.

Blood interleukin-6 and tumor necrosis factor-alpha elevation after intracerebroventricular injection of Escherichia coli endotoxin in the rat is determined by two opposing factors: peripheral induction by LPS transferred from brain to blood and inhibition of peripheral response by a brain-mediated mechanism.

Following intracerebroventricular injection of LPS in rats, IL-6 and TNF-alpha appear in peripheral blood. To determine whether these changes are mediated by passage of the injected LPS from the brain to the blood, the time course of appearance in blood of bioactive LPS after intracerebroventricular injection was compared with the time course of appearance of IL-6 and of TNF-alpha in blood. Bioactive LPS was detected 30 min after intracerebroventricular injection, the first time interval tested.

Blood to brain transfer of leptin in normal and interleukin-1beta-treated male rats.

To test the hypothesis that leptin was secreted from the brain into the blood of the rat, its concentration was measured in the superior sagittal sinus (SSS; which drains the cerebral cortex) and aortic blood of normal fasting male rats and rats that had been treated with iv or intracerebroventricular (icv) injections of interleukin-1beta (IL-1beta; 100 ng), a cytokine previously shown to induce peripheral leptin secretion. Plasma levels of leptin in SSS were slightly, but significantly, less than those in the aorta in control, saline-injected rats (0.99+/-0.

Cells containing immunoreactive estrogen receptor-alpha in the human basal forebrain.

The distribution of estrogen receptor protein-alpha (ER-alpha)-containing cells in the human hypothalamus and adjacent regions was studied using a monoclonal antibody (H222) raised against ER-alpha derived from MCF-7 human breast cancer cells. Reaction product was found in restricted populations of neurons and astrocyte-like cells. Neurons immunoreactive for ER-alpha were diffusely distributed within the basal forebrain and preoptic area, infundibular region, central hypothalamus, basal ganglia and amygdala.

Mechanisms by which blood levels of interleukin-6 (IL-6) are elevated after intracerebroventricular injection of IL-1beta in the rat: neural versus humoral control.

Intracerebroventricular (icv) injection of interleukin-1beta (IL-1beta) in rats induces elevated IL-6 levels in peripheral blood, exceeding those induced by iv or ip injection. Two hypotheses postulated to explain this phenomenon were tested. Mediation by peripheral sympathetic activation was excluded by showing that agents that blocked preganglionic cholinergic synapses (chlorisondamine), beta-adrenergic receptors (propanalol, butoxamine), and alpha-adrenergic receptors (phentolamine) did not prevent the IL-6 response.

Neuroendocrinology of infection and the innate immune system.

This chapter deals with two topics: the evolutionary and functional implications of the effects of bacterial endotoxin on the neuroendocrine system in higher vertebrates and a newly recognized neuroendocrine mechanism of immune regulation by the direct secretion of immunoregulatory cytokines from the brain. Endotoxin is a highly specific stimulus to hypothalamic-hypophysial activity; neuroendocrine responses are integrated with behavioral, body temperature, and innate immune responses. All depend upon the genetically programmed capacity of several classes of cells to distinguish molecular patterns foreign to self that are characteristic of pathogenic microorganisms.

[A "typical" case of pulmonary embolism].

A 85-year-old woman was admitted to our hospital because of a presumtive diagnosis of pulmonary thromboembolism. The patient presented with a history of progressive dyspnoea and retrosternal pain. 3-4 weeks ago she had noticed a swollen left leg.

[Progressive muscular weakness due to subacute postinfectious polyradiculitis and myelitis].

In a 67-year-old patient, generalised stable muscular weakness preexisting for several years became rapidly progressive within a few weeks prior to hospitalisation. He died one month after admission from acute cardiocirculatory failure. There was no history of muscular pain, clinical examination showed weak or absent tendon reflexes, hyposensibility of the dorsa of his feet, fasciculations and myocloni of the muscles of the lower limbs as well as a generalised muscular atrophy.

Clearance of [125I]-tumor necrosis factor-alpha from the brain into the blood after intracerebroventricular injection in rats.

To test the hypothesis that brain to blood clearance is a mechanism by which brain inflammation and damage can increase circulating acute phase cytokines, rate of transfer of [125I]-tumor necrosis factor-alpha ([125I]-TNF) from brain to blood was determined. Acid precipitable [125I]-TNF appeared in peripheral blood within 5 min of intracerebroventricular (i.c.

Alternative pathways of neural control of the immune process.

Less well established alternative neuromodulatory pathways are neuropeptide-mediated axon reflexes of sensory neurons, gut immunotrafficing, gut transmucosal transport of endogenous bacterial toxin, and the direct secretion of immunoregulatory cytokines by the brain. TNF-alpha and IL-1ra enter peripheral blood after their intracerebroventricular (i.c.

The relationship between growth hormone kinetics and sarcopenia in postmenopausal women: the role of fat mass and leptin.

Sarcopenia, the decline in body cell mass (BCM) and especially in muscle mass with age, is an important age-related cause of frailty and loss of independence in the elderly. Because the decline in BCM with age parallels a decline in GH secretion from young adulthood to old age, loss of GH secretion has been considered an important contributory cause of sarcopenia in the elderly. To test this hypothesis in a group of healthy postmenopausal women (n = 15; mean +/- SD age, 66.

[Pulmonary tuberculosis with resistance to 4 antitubercular drugs].

A 32-year-old immigrant from Pakistan was admitted to our hospital with cavernous pulmonary tuberculosis. He gave a history of several 1 to 2-months courses of antimycobacterial treatment administered earlier in Pakistan. We initiated combined therapy including isoniazid, rifampin, pyrazinamide, and ethambutol.

Changes in public psychiatric hospitalization in Oregon over the past two decades.

Objective: In 1988 a governor's commission in Oregon recommended dramatic changes in the state's approach to public psychiatric hospitalization. To evaluate the effect of the recommendations, this study examined characteristics of hospitalization for patients with schizophrenia and bipolar disorder in public psychiatric facilities between 1981 and 1984 and between 1991 and 1994.

Methods: Patients with schizophrenia and bipolar disorder (N=621) were identified as part of a larger study that examined civil commitment in one of Oregon's state hospitals in 1986.

Clearance of 125I-labeled interleukin-6 from brain into blood following intracerebroventricular injection in rats.

To test the hypothesis that interleukin-6 (IL-6) induced within the brain can be released into peripheral blood, 125I-labeled IL-6 was injected into the lateral cerebral ventricle of rats, and its concentration in peripheral blood followed serially. Acid-precipitable tracer appeared within 5 min of injection and entered the blood following first-order kinetics (fractional rate, 0.0116 +/- 0.