A kinetic threshold between negative and positive selection based on the longevity of the T cell receptor-ligand complex.

We have developed a unique in vivo system to determine the relationship between endogenous altered peptide ligands and the development of major histocompatibility complex class II- restricted T cells. Our studies use the 3.L2 T cell receptor (TCR) transgenic mouse, in which T cells are specific for Hb(64-76)/I-Ek and positively selected on I-Ek plus self-peptides. To this endogenous peptide repertoire, we have individually added one of six well-characterized 3.L2 ligands. This transgenic approach expands rather than constrains the repertoire of self-peptides. We find that a broad range of ligands produce negative selection of thymocytes in vivo. When compared with the in vitro TCR-ligand binding kinetics, we find that these negatively selecting ligands all have a half-life of 2 s or greater. Additionally, one of two ligands examined with no detectable binding to the 3.L2 TCR and no activity on mature 3.L2 T cells (Q72) enhances the positive selection of transgenic thymocytes in vivo. Together, these data establish a kinetic threshold between negative and positive selection based on the longevity of TCR-ligand complexes.

Misdiagnosis of pericardial cyst by echocardiography and computed tomography scanning.

We saw a patient who had clinical features of right-sided heart failure. Echocardiography and computed tomography findings were incorrectly interpreted as demonstrating an intracardiac mass. At surgery, a pericardial cyst externally compressing the right ventricular cavity was found. We conclude that, although noninvasive tests may play a valuable role in evaluating intracardiac masses, interpretation may be difficult and misdiagnoses are possible.

Evidence for the existence of a cardiac specific isoform of the alpha 1 subunit of the voltage dependent calcium channel.

Biochemical, pharmacological and electrophysiological evidence implies the existence of tissue specific isoforms of the L-type VDCC. The alpha 1 and alpha 2 subunits of the skeletal muscle calcium channel have been previously cloned and their amino acid sequence deduced. Here we report the isolation and sequencing of a partial cDNA that encodes a heart specific isoform of the alpha 1 subunit. The amino acid sequence deduced from this part cDNA clone shows 64.7% similarity with the skeletal muscle alpha 1 subunit. Northern analysis reveals 2 hybridizing bands, 8.5 and 13 kb, in contrast to one 6.5 kb band in the skeletal muscle. Selective inhibition of mRNA expression in Xenopus oocytes by complementary oligodeoxy-nucleotides derived from the heart clone provides further evidence that the cDNA corresponds to an essential component of the VDCC. These data further support the existence of tissue-specific isoforms of the L-type VDCC.

Milwaukee Prehospital Chest Pain Project--phase I: feasibility and accuracy of prehospital thrombolytic candidate selection.

This study prospectively determined the feasibility and accuracy of prehospital thrombolytic therapy candidate selection by base station emergency physicians. During a 6-month period, paramedics acquired and transmitted prehospital 12-lead electrocardiograms (ECGs) and then applied a thrombolytic therapy contraindication checklist. Emergency physicians interpreted prehospital ECGs and prospectively selected candidates for thrombolytic therapy. A safety committee of cardiologists reviewed prehospital ECGs, checklists and hospital records to determine accuracy independently. Six hundred-eighty stable adult prehospital patients with a chief complaint of nontraumatic chest pain were initially evaluated. Two hundred forty-one patients were excluded because of (1) unsuccessful electrocardiographic transmission (149), (2) transport to nonparticipating facilities (72), and (3) unavailable medical records (20). No prehospital thrombolytic therapy was administered in this study. Of 439 cases, 91 (21%) had the final diagnosis of acute myocardial infarction, 38 (8.7%) had diagnostic prehospital ECGs, and 12 (2.7%) were selected by emergency physicians as candidates for thrombolytic therapy. Seventy percent of patients with myocardial infarction had checklist exclusions for thrombolytic therapy. Prehospital evaluation increased mean scene time (paramedic arrival on scene to scene departure) by 4 minutes. The median time from chest pain onset to paramedic arrival in patients with myocardial infarction was 60 minutes. The estimated average time saved if prehospital thrombolytic therapy had been available was 101 +/- 81 minutes. The safety committee concluded that acceptable accuracy of emergency physician prehospital electrocardiographic interpretation, checklist and case selection was achieved. It is concluded that emergency physicians can accurately identify candidates for prehospital thrombolytic therapy.

Underreporting the use of dietary supplements and nonprescription medications among patients undergoing a periodic health examination.

OBJECTIVE: To compare the use of dietary supplements and nonprescription medications as reported on a written medical questionnaire with use reported during a structured interview. DESIGN: We conducted a prospective study of 200 subjects randomly selected among patients undergoing a periodic health examination in two divisions of the Department of Internal Medicine at Mayo Clinic Rochester--100 patients from a national cohort of executives and 100 community patients. MATERIAL AND METHODS: Written information on self-reported use of supplements and nonprescription medications was obtained as part of a comprehensive medical questionnaire. Subjects were then interviewed and asked about the use of supplements and nonprescription medications. In addition, the reason for using supplements was elicited and recorded. RESULTS: The prevalence of use of dietary supplements was 30.5% by written self-report in comparison with 61.0% reported during the structured interview. The results were consistent between executive and community patients. In response to questions about taking nonprescription medications, 24.5% of patients reported such use on the medical questionnaire in comparison with 42.5% when interviewed. The most common dietary supplements taken were multivitamins (41.5%), followed by vitamin E (24.0%) and vitamin C (23.0%). The most common nonprescription medications taken were aspirin (16.5%) and ibuprofen (13.0%). Most frequently, patients indicated that they were using supplements to promote health. CONCLUSION: In this study, half the patients who took dietary supplements and almost half who took nonprescription medications did not report them to their healthcare provider on a written questionnaire, even though this information was requested. Patients should be specifically asked about use of dietary supplements and nonprescription medications, even if written information about such use is provided.

Retroclival arachnoid cyst.

Retroclival arachnoid cyst is a rare mass lesion, with only seven cases previously reported in literature. MR is the imaging modality of choice in its evaluation and in its differentiation from epidermoid cyst. The case reported here was surgically proved and had an uncharacteristic MR signal intensity that was higher than that of cerebrospinal fluid due to previous hemorrhage.

Predictors of differential response to cognitive, experiential, and self-directed psychotherapeutic procedures.

Group cognitive therapy (CT), focused expressive psychotherapy (FEP; a form of group experiential psychotherapy), and supportive, self-directed therapy (S/SD) were compared among 63 patients with major depressive disorder (MDD). Variation among patients' coping styles (externalization) and defensiveness (resistance potential) was used in a prospective test of hypothesized differential treatment-patient interactions. Results suggest that patient characteristics can be used differentially to assign psychotherapy types. Externalizing depressed patients improved more than nonexternalizing depressed patients in CT, whereas nonexternalizing (internalizing) patients improved most in S/SD. Conversely, high defensive (resistant) patients improved more in S/SD than in either FEP or CT, whereas low defensive patients improved more in CT than in S/SD.

Identification of patients at risk for nonresponse and negative outcome in psychotherapy.

This study evaluated the use of pretherapy patient variables as correlates of 3 categorical types of outcome: negative response (negative change of more than 1 normative SEest on depression measure); nonresponse (change within +/- 1 SEest on depression measure); and positive response (positive change of more than 1 SEest on depression measure) to psychotherapy among 62 patients with major depressive disorder. By using 4 scales from the Brief Symptom Inventory, the Inventory of Interpersonal Problems, age, and sex, 75.8% of the Ss were correctly classified into the 3 groups. Negative responders were characterized by high levels of interpersonal difficulty and low levels of subjective distress. Nonresponders displayed moderate levels of both interpersonal difficulties and subjective distress. Positive responders displayed high levels of both interpersonal difficulties and subjective distress.

Rigid head fixation for intraoperative computed tomography.

A C-ring radiolucent head holder was designed to facilitate intraoperative computed tomography (CT) during resection of various intracerebral lesions. Important features of the procedure include rigid skull and CT table fixation, cranial access, and low artifact CT imaging performed during and after operation. A case of CT-assisted resection of an arteriovenous malformation is described.

Behavior, affect, and cognition among psychogenic pain patients in group expressive psychotherapy.

In an exploratory study, the authors examined the cognitions, affect, and behaviors reported by eight female depressed chronic pain patients during experiential therapy sessions that focused on anger and depression. Subjects appeared to fit previously developed psychologic profiles of patients with chronic pain disorder: they presented as conscientious, compliant, passive, and rule-bound, viewing life and emotional expression as dangerous, avoiding conflict and risk, denying their own emotional needs. Their reports were compared with the self-reported affect behavior and cognitions of eight depressed female patients without chronic pain, under similar therapeutic conditions. Considerable differences in style and content were found. Implications of these findings for clinical practice are discussed.

Feeding and drinking interactions after acute butyrophenone administration.

The effects on feeding and drinking of various doses of droperidol, haloperidol and spiroperidol were studied in a number of paradigms. All three buryrophenones produced generally similar effects. After food deprivation, feeding was slightly increased at low doses but was decreased at the higher doses; the concomitant postprandial drinking was attenuated at all doses. Desalivate rats showed a marked attenuation of feeding (and prandial drinking) at low doses, but when wet mash was given instead of pellets and water a normal dose-response relationship was obtained. After water deprivation drinking was attenuated at all doses, and when food was also available during the drinking test the food intake was decreased in proportion to the drinking. Drinking was blocked more when food was present than in its absence. Insulin and 2-deoxyglucose induced feeding in sated rats was attenuated but not abolished by haloperidol. The findings are discussed relative to the role of activation and brain catecholamines in feeding and drinking.

Cardiac remodeling as a consequence and cause of progressive heart failure.

Natural history studies in heart failure have shown that increases in left ventricular (LV) volume and LV mass are directly related to future deterioration in LV performance and a less favorable clinical course. Despite the recognized importance of remodeling in heart failure, very little is known about the basic mechanisms that lead to cardiac remodeling. In this review, we will summarize recent clinical and experimental studies that highlight the importance of the remodeling process during the progression of heart failure. The intent of this review is to provide an integrated view of the mechanisms that contribute to LV remodeling at the cellular level, the myocardial level, and the level of the chamber.

The intensification and resolution of blocked affect in an experiential psychotherapy.

Focused Expressive Psychotherapy is a Gestalt-based method of psychotherapy which is designed to facilitate the resolution of constricted emotion in patients. This form of therapy is described as a five-step process. The present article addresses the steps of that process which relate specifically to the intensification and resolution of emotions. The importance and rationale for intensification are discussed and related to the concept of restructured schematic memories. Markers of resolution are identified as changes in 'benchmarks', changes in patient behaviour or attitude, and/or a reevaluated stance towards past events. We conclude by citing one of our recent research efforts that demonstrates a relationship between the intensification of emotion and positive therapy outcome.

Influence of habitat modification on the community of gastrointestinal helminths of cotton rats.

Dynamics of communities of gastrointestinal helminths of cotton rats (Sigmodon hispidus) were monitored in response to five experimental brush management treatments using herbicide applications with and without prescribed burning on the Cross Timbers Experimental Range in Payne County, Oklahoma (USA). A total of 113 adult cotton rats (68 male and 45 female) was collected from experimental pastures in winter and summer 1986 resulting in the recovery of five species of helminths: Longistriata adunca, Syphacia sigmodontis, Strongyloides sp., Protospirura muris, and Raillietina sp. Prevalences of Raillietina sp. and S. sigmodontis were greater on control than herbicide-treated pastures. Prevalence and abundance of Raillietina sp. and prevalence of S. sigmodontis were significantly lower on annually burned, herbicide-treated pastures compared to unburned herbicide-treated pastures. Triclopyr-treated pastures had greater abundances of L. adunca and lower abundances of Raillietina sp. than those treated with tebuthiuron. Abundances of L. adunca also decreased from winter to summer on annually burned, herbicide-treated pastures while increasing on other pastures. Distribution of all helminths was overdispersed, but distribution of L. adunca showed a significant brush treatment by season interaction as a result of greater overdispersion in summer than winter for cotton rats inhabiting brush-treated pastures. Our results indicate that man-induced habitat modifications can alter host-parasite relationships in the community.

Influence of habitat modification on the intestinal helminth community ecology of cottontail rabbit populations.

The influence of five brush management treatments using the herbicides tebuthiuron and triclopyr, with or without prescribed burning, on the intestinal helminth community of cottontail rabbits (Sylvilagus floridanus) was studied in 1987 on the Cross Timbers Experimental Range in Payne County, Oklahoma (USA). Six helminth species were found (Dermatoxys veligera, Trichostrongylus calcaratus, Passalurus nonanulatus, Wellcomia longejector, Taenia pisiformis cystercercus, and Mosgovoyia pectinata americana) in 102 rabbits (88 adult and 14 juveniles) collected over two seasons (winter and summer). Prevalence of M. pectinata americana in cottontail rabbits was significantly greater in untreated control pastures than herbicide treated pastures in winter, while prevalence of T. pisiformis was significantly greater in burned than unburned pastures. Abundances of helminth species in the intestinal tract of cottontail rabbits were unaffected by brush treatments. Mosgovoyia pectinata americana abundance demonstrated a highly significant increase from winter to summer; conversely, abundance of all oxyurid pinworms combined (D. veligera, P. nonanulatus, W. longejector) was significantly higher in winter than summer. Helminth community dynamics were significantly influenced by season, but were unaffected by brush treatments. Habitat modification could have influenced cestode transmission by altering the ecology of invertebrate and vertebrate hosts.

Psychosocial aspects of the organ transplant experience: what has been established and what we need for the future.

This article briefly describes the current status and limitations of the organ transplant process that has now become a routine medical procedure. The article discusses how transplantation is not a cure for end-stage organ disease but an alternative form of treatment with both potential medical and psychosocial problems. Both transplant candidates and recipients encounter psychosocial problems. The article examines how these psychosocial problems affect transplant patients prior to transplant, immediately following surgery, and posttransplant. The psychosocial problems include psychiatric diagnoses, individual and family adjustment and relationship problems, sexual dysfunction, return-to-work (RTW) difficulties, and compliance problems and variables related to noncompliance. The article also reviews the special problems of pediatric and adolescent transplant recipients. The need for empirically supported interventions is noted in each of the problem areas. The author outlines problems with previous research studies that hamper solid interpretations of the data, and discusses literature suggesting that the psychosocial problems of transplant candidates and recipients are likely to be underreported. The article concludes with recommendations about the need to switch research efforts toward intervention studies in the problem areas already solidly identified by the literature.