John Adair

Aseptic meningitis following cardiac transplantation Clinical characteristics and relationship to immunosuppressive regimen

Neurologic disorders are uncommon but alarming complications of cardiac transplantation. Of 29 patients from the Utah Cardiac Transplant Program (UCTP) who had lumbar puncture because of change in neurologic function, or to assess fever of uncertain etiology, CSF pleocytosis was present in 14 patients, 4 of whom had an active infectious process involving the nervous system. In 10 other patients, CSF pleocytosis with negative cultures appeared following treatment with OKT3 monoclonal antibody. The most prominent clinical signs of this aseptic meningitis syndrome are fever and transient cognitive dysfunction.

EFFECT OF NEONATAL HYPOXIA-ISCHEMIA ON NIGRO-STRIATAL DOPAMINE RECEPTORS AND ON STRIATAL NEUROPEPTIDE Y, DYNORPHIN A AND SUBSTANCE P CONCENTRATIONS IN RATS

Perinatal hypoxic-ischemic brain injury was induced in 7- to 8-day-old rats by ligating the left carotid artery with subsequent exposure to 9% oxygen atmosphere for 2.5 h. The animals were killed 7 days later and grouped according to the degree of brain injury sustained after hypoxia-ischemia. Total protein content measured in striatum ipsilateral to the ligation, and dissected from brains showing extensive damage, was reduced to 64% of contralateral tissue. The protein content was not altered in other groups including control animals exposed to air and in sham-operated animals exposed to hypoxic conditions. The concentration of (pg/mg protein) and total (pg/striatum) striatal dynorphin A-like immunoreactivity (DLI) from brains with extensive damage were increased to 481% and 285% of the contralateral side, respectively. Hypoxia-ischemia increased striatal neuropeptide Y-like immunoreactivity (NPYLI) concentration from brains with extensive damage to 157% of contralateral side, but when the results were expressed as total NPYLI content per striatum, NPYLI content in striatum with extensive damage remained unaltered. Substance P-like immunoreactivity (SPLI) concentration and total content per striatum from brains with extensive damage were reduced to 66% and 43% of the contralateral side, respectively. D1 and D2 receptor density in animals killed 10 days after injury was reduced by 24% and 22% of control, respectively, in striatum from brains with extensive damage. These results indicate complex changes in brain neuropeptides following neonatal hypoxia-ischemia. Damage in the substance P system could have functional effects on dopaminergic transmission while the increase in NPYLI and in DLI concentrations may respectively reflect the relative preservation from neuronal damage and possibly an increase in neuropeptide synthesis or decrease in release. The decrease in SPLI concentration and the increase DLI concentration induced by hypoxia-ischemia suggests that these peptides may be present in separate neurons.

The temporal evolution of striatal dopamine receptor binding and mRNA expression following hypoxia-ischemia in the neonatal rat

Neonatal hypoxic-ischemic (HI) brain injury in the rat alters dopamine receptors. To determine whether such changes are permanent, dopamine receptors and corresponding mRNA were examined at various time points after neonatal HI using receptor autoradiography and in situ hybridization. Rat pups underwent ligation of the left common carotid artery followed by hypoxic exposure (8.5% O2 for 3 h). Controls underwent sham surgery alone. Animals surviving for 2-80 days following HI were studied. Striatal D1 receptors (labeled by [3H]SCH23390) were reduced as early as 2 days following HI, remained depressed for 21 days, but recovered to control levels by young adulthood (3 months of age). D2 receptors (labeled by [125I] iodosulpride) did not decline until 10 days after HI, and remained uniformly depressed throughout the caudate-putamen thereafter. Changes in D1 receptor mRNA transcripts closely paralleled alterations in receptors: early reductions in D1 mRNA signal recovered by young adulthood. D2 mRNA exhibited a unique temporal profile with an early decrease (2 days following HI), and prompt, persistent recovery. Dopamine receptors and transcripts are differentially affected by HI injury early in development. Whereas D1 receptor expression recovers from neonatal HI injury, D2 receptors remain permanently affected despite the presence of normal levels of D2 receptor transcripts. A persistent, post-transcriptional effect of HI on D2 receptor expression is suggested.

Cerebrovascular syndromes following cardiac transplantation

Between 1985 and 1990, there were 275 orthotopic cardiac transplantations performed on 263 patients. To determine the frequency and define the clinical spectrum of cerebrovascular disease among these patients, we followed them over an average period of 18.5 months (range, 1 to 59 months). Cerebrovascular disorders developed in 24 of 263 patients. We established and classified stroke etiology directly related to transplant procedures or therapies in 13 cases. Nine of 11 cases not directly attributable to transplantation had presumed thromboembolic ischemic events. While stroke most commonly results from conditions unique to heart transplant patients, some disorders may develop from vascular conditions that antedate transplantation.

Effects of Hypoxic-Ischemic Brain Damage on Dopaminergic Markers in the Neonatal Rat: A Regional Autoradiographic Analysis

Dopamine has been implicated as an endogenous substance that may mediate neuronal death after hypoxic-ischemic insult. Using semiquantitative autoradiography, we studied the effect of perinatal hypoxic-ischemic injury on dopamine binding sites in rat brain. Experimental injury resulted in a substantial decrease in dopamine type-1 (D1) and forskolin (adenylate cyclase) binding sites. In contrast, markers for dopamine type-2 (D2) sites and for dopamine uptake were unaffected in lesioned animals. Changes within dopaminergic pathways were variable, with reduction in binding being encountered mainly in components of the extrapyramidal motor system: caudate-putamen, -61%; globus pallidus, -64%; entopeduncular nucleus, -60%; and substantia nigra, -69%. Furthermore, the topography of D1 receptor loss within the caudate-putamen was not uniform, with the greatest decrement in dorsolateral regions. Reduced D1 versus D2 receptor activation may underlie extrapyramidal movement disorders that appear as a consequence of perinatal hypoxic-ischemic insult. (J Child Neurol 1992;7:199-207).

Acute encephalopathy associated with the eosinophilia‐myalgia syndrome

Discussion. Our data indicate the following: (1) light-microscopic immunolocalization of Ub in patient muscle biopsies is a n easy method, and the only one presently available, to identify characteristic CTFs and, consequently, to distinguish IBM from polymyositis by light microscopy; and ( 2 ) the fact that CTFs are highly ubiquitinated places them in the Ub-mediated turnover pathway and may facilitate understanding of their composition and pathogenesis.

Size and distribution of lacunes defined by computed tomography: Correlation with blood pressure and possible stroke mechanisms

To study the causes of lacunes (small cerebral infarcts) and the frequency of large brain infarcts in the same patients, the records of all patients admitted to the University of Utah Hospital between January 1983 and June 1986 with the diagnosis of acute cerebral or brainstem infarction were retrospectively reviewed. The neuroradiologists interpretation of each patients computed tomography (CT) scan was used to identify a cohort of 69 patients with lacunes. The medical records were examined for data pertaining to clinical events, and the CT scans were inspected to determine the dimensions and anatomic distribution of the infarcts. Patients who had larger infarcts or intracranial hemorrhages, in addition to one or more lacunes, were included. Twenty-seven patients (39%) were normotensive; 29 (42%) were hypertensive, and 13 (19%) had a history of hypertension but were normotensive at the time of the stroke. Ninety-five lacunes were distributed evenly among these three groups. The lacunes were larger in the normotensive patients. Twenty large infarcts were distributed evenly in the three groups. Diagnostic evaluation revealed significant abnormalities. The presence of cardiac and/or arterial disease places patients with lacunes at greater risk for more serious cerebral ischemic events and for recurrent small strokes. These observations are discussed as they relate to the causes and significance of lacunes.