Congenital esophageal stenosis presenting as noncardiac,esophageal chest pain

Summary A case of a 31-year-old female with congenital esophageal stenosis presenting with symptoms of chest pain caused by esophageal dysmotility is described. The involved segment in congenital esophageal stenosis has a characteristic thickening of the muscularis propria layer, as seen by EUS examination. In these patients, symptoms of dysphagia can be managed with esophageal dilation and noncardiac esophageal chest pain responds to pharmacotherapy with diltiazem.The opinions and assertions contained herein are the private ones of the authors and are not to be construed as official policy or reflecting the views of the Army or the Department of Defense.     

Elevation of plasma thioredoxin levels in HIV-infected individuals

Thioredoxin (Trx), a ubiquitous protein intimately involvedin redox and protein disulfide reductions, has been shown tobe released from cells and to have cytokine-like activities.In addition, Trx has been implicated in the redox regulationof immunological responses and shown to be deficient in tissuesfrom AIDS patients. In studies presented here, plasma Trx levelswere measured by ELISA in plasma samples from HIV-infected individuals(n = 136) and HIV-negative controls (n = 47). To account forthe release of Trx into plasma due to hemolysis, the Trx measurementswere corrected according to the level of hemoglobin in the plasmasample. Data presented show that, in contrast to tissue Trxlevels, corrected plasma Trx levels are significantly higherin HIV-infected individuals than in controls (P < 0.0001).Furthermore, {small tilde}25% of the HIV-infected individualsstudied have plasma Trx levels greater than the highest levelfound in controls (37 ng/ml). Detailed multiparameter FACS analysisof peripheral blood mononuclear cells (PBMC) from the infectedindividuals demonstrates that those with higher plasma Trx levels(37 ng/ml or greater) tend to have lower overall CD4 counts.In addition, increases in plasma Trx levels correlate with decreasesin monochlorobimane staining (indicative of lower intracellularglutathione levels in PBMC) and with changes in surface antigenexpression (CD62L, CD38 and CD20) that occur in the later stagesof HIV infection. These correlations suggest that elevationof plasma Trx levels may be an important component of advancedHIV disease, perhaps related to the oxidative stress that oftenoccurs at this stage.     

A New Technique for CT/MR Fusion For Skull Base Imaging

This paper presents our initial experience utilizing a new technique which allows CT and MR image fusion in patients with skull base lesions. Eleven patients with a variety of skull base lesions underwent CT and MR imaging prior to surgery. Both sets of images were coregistered using customized software. The CT and MR data sets were then combined and viewed in a single interactive image formar using a high-speed graphic computing system. Image fusion allowed simultaneous visualization of the bony skull base anatomy (CT) and detailed soft tissue anatomy (MR) using a single image format. Combining both modalities was felt to provide a better assessment of the extent of lesions and improve understanding of their relationship to adjacent bony and neurovascular anatomy. Specifically, image fusion enhanced awareness of location of skill base lesions with respect to the cavernous sinuses. Gasserian ganglia, carotid arteries, and jugular foramina. For tumors arising within the internal auditory canal (IAC), fused images allowed better delineation of the lateral aspect of the lesion with respect to the fundus of the IAC. Thus, fusion of CT and MR studies provides a unique image format which has advantages over single modality display. We believe image fusion is beneficial for surgical planning and for treatment planning of complex skull base malignancies treated with radiotherapy.     

A glutamatergic mechanism for aluminum toxicity in astrocytes

The effect of aluminum on the metabolism of glutamate and glutamine in astrocytes was studied to provide information about a possible biochemical mechanism for aluminum neurotoxicity and its potential contribution to neurodegenerative disease. Exposure of cultured rat brain astrocytes for 3–4 d to 5–7.5 mM aluminum lactate increased glutamine synthetase activity by 100–300% and diminished glutaminase activity by 50–85%. Increased glutamine synthetase enzyme activity was accompanied by an elevated level of glutamine synthetase mRNA. Alterations in glutaminase and glutamine synthetase following aluminum exposure caused increased intracellular glutamine levels, decreased intracellular glutamate levels, and increased conversion of glutamate to glutamine and the release of the latter into the extracellular space. The results of these changes may alter the availability of neurotransmitter glutamate in vivo and may be a mechanism for the aluminum neurotoxicity observed in individuals exposed to the metal during dialysis procedures and other situations.     

Neurochemical mechanisms mediating the behavioral and cognitive effects of nicotine

Data are reviewed, largely from experiments in the authors'laboratory, that suggest three modes of action of systemic nicotine in producing three different types of effect upon behavior and cognitive function. (1) Preexposure of a stimulus without consequence makes it harder subsequently to form associations to that stimulus, a form of selective attention known as latent inhibition. Latent inhibition is blocked by nicotine, an effect that is apparently mediated by a nicotine-induced increase in dopamine release in the nucleus accumbens. (2) A single dose of nicotine proactively increases the partial reinforcement extinction effect measured several weeks later: that is, resistance to extinction is decreased by nicotine in animals that have been trained on a continuous reinforcement schedule, and increased in animals trained on a partial reinforcement schedule. This effect appears to be due to increased synthesis of tyrosine hydroxylase in the cell bodies of noradrenergic neurons in the locus coeruleus, followed by axonal transport to the hippocampus and increased synthesis and release of noradrenaline in that structure. (3) Nicotine improves vigilance in animals with cognitive deficits due to destruction of the forebrain cholinergic projection system, either as a consequence of excitotoxic lesions of the nuclei of origin of this system or after prolonged alcohol consumption; and also in human subjects with Alzheimer's disease (in which this system undergoes degeneration). This effect is most likely due to an action at denervated cholinergic synapses in the hippocampus and neocortex. © 1994 Wiley-Liss, Inc.     

Infectious scleritis: Report of four cases

While systemic autoimmune diseases are the main possibilities in the differential diagnosis of scleritis, other less common etiologies such as infections must also be considered. The authors report four cases of infectious scleritis to review predisposing factors, clinical characteristics, methods of diagnostic approach, and response to therapy. Two patients had primary scleritis and two patients had secondary scleritis following extension of primary corneal infection (corneoscleritis). Diagnoses included three local infections (one each withStaphylococcus. Acanthamoeba, and herpes simplex) and one systemic infection (Lyme disease). Stains, cultures, or immunologic studies from scleral, conjunctival, and/or corneal tissues, and serologic tests were used to make the diagnosis. Medical therapy, including antimicrobial agents, was instituted in all patients, and surgical procedures were additionally required in two patients (scleral grafting in one and two penetrating keratoplasties in another); the patient who required two penetrating keratoplasties had corneoscleritis and underwent eventual enucleation. Infectious agents should be considered in the differential diagnosis of scleritis.     

Single- vs Multiple-Dose Pharmacokinetics of Clozapine in Psychiatric Patients

Clozapine plasma levels were monitored in 16 patients during a series of three consecutive treatments (single dose-multiple dose-single dose). Each patient received a single 75-mg dose (3 x 25 mg) with clozapine tablets, and serial plasma samples were collected over 48 hr after the dose. At 48 hr, a multiple-dose regimen was started, consisting of an initial dose escalation period followed by dosing at a constant regimen for at least 6 days. After the last dose, serial plasma samples were again obtained over 72 hr. Drug was then withheld for at least 7 days, a final single 75-mg dose was given, and plasma sampling was repeated. A subset of the patient population (N = 7) was used to test for a food effect during the single-dose treatments. The pharmacokinetic parameters between the initial and the final single dose periods were not significantly different. Similarly, there were no differences within patients when given the dose after fasting (fed 1 hr after dose) or with a meal. In contrast, the terminal elimination rate differed between the single-dose and the multiple-dose treatments (t1/2 m3 = 7.9 hr single dose and 14.2 hr multiple dose) (P less than 0.05) and the dose-normalized area under the plasma concentration/time curves increased 27% with multiple dosing. Since a previous study in patients (Choc et al., Pharm. Res. 4:402-405, 1987) showed dose proportionality of clozapine plasma concentrations during multiple-dose regimens, the present results cannot be described by Michaelis-Menten kinetics.