Keratinocyte-derived Cytokines and UVB-Induced Immunosuppression

Ultraviolet radiation (UVB) in sunlight is known to have multiple effects on the immune system. Evidence suggests that UVB-induced immunosuppression is mediated in part by immunosuppressive and immunoregulatory cytokines. Our studies have utilized gene-targeted mutant mice to determine key molecular requirements essential for the development of UVB-induced immunosuppression. Preliminary results from our laboratory suggest that TNF-α plays a regulatory role in contact hypersensitivity, but is not a crucial factor for UVB-induced immunosuppression, and that multiple factors are involved in the induction of UVB mediated immunosuppression.     

Protective genes expressed in endothelial cells of second hamster heart transplants to rats carrying an accommodated first graft

Abstract: Accommodation refers to survival of a xenograft despite the presence of anti-donor organ antibodies and complement. We have recently shown that accommodation of a hamster heart transplanted to a rat receiving short-term cobra venom factor (CVF) and continuing cyclosporine A (CyA) therapy is associated with i) the expression in the endothelial cells (EC) and smooth muscle cells of the graft of a number of "protective" genes, ii) a prominent intragraft Th2 cytokine profile, and iii) the relatively heavy deposition of IgG2c antibodies on the EC of the graft. In contrast, rejecting grafts do not express the protective genes, have a Th1 cytokine profile, and apparently have lesser amounts of IgG2c. These findings are consistent with host factors (Th2 cytokines and IgG2c) contributing to xenograft accommodation. To test whether these host factors may predispose to the development of accommodation, we placed a second hamster heart into each of 12 rats carrying a surviving first heart; recipients were, at the time, receiving only CyA. Whereas first grafts transplanted to rats receiving only CyA survive for 3 to 4 days, 11 out of 12 second transplants survived more than 20 days, and the other survived for 7 days. Nine of the twelve were not rejected: of these, four were removed between day 35 and 132 for study, and the remainder are still beating at 35 to 52 days. The surviving second hearts we studied had accommodated in that the picture on immunopathology was the same as for surviving first hearts. We suggest that the Th2 cytokines and perhaps the IgG2c response are factors in allowing prolonged survival of the second grafts and, further, that these factors contribute to the expression in the EC and smooth muscle cells of the surviving second hearts of the protective genes.     

Efficacy and Costs of Patient-controlled Analgesia versus Regularly Administered Intramuscular Opioid Therapy

Background: Many studies have shown in the efficacy of patient-controlled analgesia (PCA). However, it is not clear whether PCA has clinical or economic benefits in addition to efficient analgesia. The current study was designed to evaluate these issues by comparing PCA with regularly administered intramuscular injections of opioids after hysterectomy.

Methods: This prospective study included 126 patients who underwent abdominal hysterectomy and were randomly assigned to receive PCA or regularly timed intramuscular injections of morphine during a period of 48 h. Doses were adjusted to provide satisfactory analgesia in both treatment groups. Pain at rest and with movement, functional recovery, drug side effects, and patient satisfactory were measured using rating scales and questionnaires. The costs of PCA and intramuscular therapy were calculated based on personnel time and drug and material requirements.

Results: Comparable analgesia was observed with the two treatment methods, with no significant differences in the incidence of side effects or patient satisfaction. The medication dosage had to be adjusted significantly more frequently in the intramuscular group than in the PCA patients. The PCA did not favor a faster recuperation time compared with intramuscular therapy in terms of times of ambulation, resumption of liquid and solid diet, passage of bowel gas, or hospital discharge. The results of the economic evaluation, which used a cost-minimization model and sensitivity analyses, showed that PCA was more costly than regular intramuscular injections despite the fact that no costs for the pump were included in the analyses. Cost differences in nursing time favoring PCA were offset by drug and material costs associated with this type of treatment.     

Serum modulates cyclic AMP-dependent morphological changes in cultured neurohypophysial astrocytes

The effects of serum on the morphological plasticity exhibited by pituicytes in explant cultures of the neurohypophysis of adult rats have been examined. Cultured pituicytes are normally nonstellate, protoplasmic, amorphous cells (< 25% are stellate with a distinct cell body and phase bright processes). After incubation (90 min) of pituicyte cultures in a HEPES buffered salt solution (HBSS) supplemented with isoproterenol or forskolin, the fraction of stellate pituicytes significantly increased. The increase in the fraction of stellate cells induced by isoproterenol was not reversed by subsequent incubation in isoproterenol-free HBSS for 90 min. In contrast, after stellation was induced in cultures by exposure to forskolin (90 min), the fraction of stellate cells was significantly reduced if these cultures were incubated in forskolin-free, serum (0.5%) supplemented HBSS for the same duration. Serum also blocked the increase in the fraction of stellate pituicytes induced by forskolin. These experiments suggest that serum components may have a significant role in controlling the plasticity of neuroglial relations in the neurohypophysis priviously demonstrated in vivo.     

Computerized follow-up of discrepancies in image interpretation between emergency and radiology departments

Radiographs are ordered and interpreted for immediate clinical decisions 24 hours a day by emergency physicians (EP’s). The Joint Commission for Accreditation of Health Care Organizations requires that all these images be reviewed by radiologists and that there be some mechanism for quality improvement (QI) for discrepant readings. There must be a log of discrepancies and documentation of follow up activities, but this alone does not guarantee effective Q.I. Radiologists reviewing images from the previous day and night often must guess at the preliminary interpretation of the EP and whether follow up action is necessary. EP’s may remain ignorant of the final reading and falsely assume the initial diagnosis and treatment were correct. Some hospitals use a paper system in which the EP writes a preliminary interpretation on the requisition slip, which will be available when the radiologist dictates the final reading. Some hospitals use a classification of discrepancies based on clinical import and urgency, and communicated to the EP on duty at the time of the official reading, but may not communicate discrepancies to the EP’s who initial read the images. Our computerized radiology department and picture archiving and communications system have increased technologist and radiologist productivity, and decreased retakes and lost films. There are fewer face-to-face consultations of radiologists and clinicians, but more communication by telephone and electronic annotation of PACS images. We have integrated the QI process for emergency department (ED) images into the PACS, and gained advantages over the traditional discrepancy log. Requisitions including clinical indications are entered into the Hospital information System and then appear on the PACS along with images and readings. The initial impression, time of review, and the initials of the EP are available to the radiologist dictating the official report. The radiologist decides if there is a discrepancy, and whether it is category I (potentially serious, needs immediate follow-up), category II (moderate risk, follow-up in one day), or category III (low risk, follow-up in several days). During the working day, the radiologist calls immediately for category I discrepancies. Those noted from the evening, night, or weekend before are called to the EP the next morning. All discrepancies with the preliminary interpretation are communicated to the EP and are kept in a computerized log for review by a radiologist at a weekly ED teaching conference. This system has reduced the need for the radiologist to ask or guess what the impression was in the ED the night before. It has reduced the variability in recording of impressions by EP’s, in communication back from radiologists, in the clinical follow-up made, and in the documentation of the whole QI process. This system ensures that EP’s receive notification of their discrepant readings, and provides continuing education to all the EP’s on interpreting images on their patients.     

Maternal satisfaction following post-shelter family reunification

The purpose of this study was to examine the correlates of post-shelter maternal family satisfaction in a group of youth who were reunified with their families following a shelter stay. Findings indicated that higher ratings of family satisfaction were related to greater maternal problem solving skill and less family conflict.     

Compensation seeking status and psychometric assessment of combat veterans seeking treatment for PTSD

Examined differences between compensation seeking (CS) veterans and noncompensation seeking (NCS) veterans on the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) and other psychological measures in 142 combat veterans evaluated for posttraumatic stress disorder (PTSD) at an outpatient Veterans Affairs (VA) hospital PTSD clinic. Patients were grouped on the basis of their compensation seeking status, with 69% classified as CS for PTSD. The CS veterans achieved significantly more pathological scores across a wide range of psychological inventories and MMPI-2 validity indices, although they did not differ in frequency of PTSD diagnoses from NCS veterans. Implications of these findings are discussed, and clinicians are advised to be aware of the compensation seeking status of combat-veterans being evaluated for PTSD.     

Iodomethylated fatty acid metabolism in mice and dogs

The myocardial uptake of fatty acids labeled with radioactive iodine and injected i.v. can only be evaluated with SPECT if their oxidation kinetics is slow enough. For this reason, we evaluated different iodomethylated fatty acids in mice and dogs to determine which of them shows the highest myocardial uptake and the slowest oxidation. The most suitable was found to be 16-iodo-3-methyl hexadecanoic acid (mono ) since its myocardial fixation was the same as that of the reference, i.e. 16-iodo-9-hexadecenoic acid (IHA), whereas it was degraded more slowly. Thirty min after injection of mono into dogs, the decrease in myocardial activity with respect to the maximum was two fold less than after IHA injection. The myocardial uptake of the two dimethylated fatty acids studied, i.e. 16-iodo-2,2-methyl hexadecanoic acid and 16-iodo-3,3-methyl hexadecanoic acid, was less than that of IHA in mice and dogs. In the latter, the myocardial uptake was so small that we were unable to study the time course of its activity. Consequently, these dimethylated fatty acids are not suitable for the study of the myocardial uptake of fatty acids in man.