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Biomedical subjects

T J Sullivan

Publications and source records attributed to T J Sullivan.

At least 109 records · Page 6Linked to original sources

Endogenous cortisol regulates immunoglobulin E-dependent late phase reactions.

To investigate the impact that physiological variation in serum cortisol has on IgE-mediated events, 10 atopic subjects underwent cutaneous antigen challenge with measurement of the early phase wheal (EPW) at 20 min and the late phase reaction (LPR) at 6 h. All subjects were challenged during control conditions between 8:00 and 9:00 a.m. Repeat challenges were performed in five subjects at 6:00 p.m. and in eight subjects after ingestion of metyrapone, a specific inhibitor of cortisol synthesis. Compared with control values, mean serum cortisol was suppressed in the evening and after metyrapone (P less than 0.05 all time points). No effect was seen on the EPW, but mean LPR diameters at three antigen dilutions were significantly increased by cortisol suppression (P less than 0.05). Replacement doses of hydrocortisone given in the evening and with metyrapone abrogated these increases. Blinded analysis of LPR biopsies from cortisol-suppressed subjects revealed increases in leukocytoclasis (P less than or equal to 0.0001), interstitial leukocytes (P less than or equal to 0.01), and eosinophils (P less than or equal to 0.04). These results indicate that physiological levels of serum cortisol can regulate IgE-dependent cutaneous inflammation by affecting the expression of cellular events at late phase sites.

Circadian Rhythm↗

Detection of human IgE to sulfamethoxazole by skin testing with sulfamethoxazoyl-poly-L-tyrosine.

Adverse reactions to sulfamethoxazole (SMX) occur in 4% to 6% of normal individuals. Many of these reactions resemble immunopathologic reactions, but skin test or in vitro evidence of a role for IgE is limited. Earlier RAST studies in our laboratory provided evidence that the N4-SMX hapten was a major determinant in immediate hypersensitivity reactions to SMX. We tested the hypothesis that IgE to this hapten is present on the mast cells of patients who have experienced immediate hypersensitivity reactions temporally related to exposure to SMX. A multivalent skin test reagent, SMX168-poly-L-tyrosine, and a univalent hapten, SMX-tyrosine, were synthesized. Forty-four patients with histories of allergic reactions to SMX and six subjects who had been exposed to the drug, but who had not reacted, were skin tested. Twenty-seven percent of the history-positive patients were skin test positive. None of the control individuals was positive. The immunologic responses to SMX in three patients who had experienced allergic reactions during SMX/trimethoprim therapy were analyzed in serial skin test and RAST assessments. One to three years after the clinical reactions, IgE to SMX could be demonstrated by skin testing in all three patients with a SMX-poly-L-tyrosine skin test reagent. Skin test reactions were inhibited by the monovalent reagent, SMX-tyrosine, in a dose-dependent manner. SMX-specific IgE antibodies could also be detected by RAST in serum obtained within days of the reactions from two of the three individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

Medical canthal resection: an effective long-term cure for medial ectropion.

The results of 37 medial canthal resection procedures performed for the correction of severe paralytic or involutional medial ectropion are presented with an average follow-up of 5.4 years. Epiphora was improved in 33 out of the 37 cases and all but one patient had an anatomically improved lid-globe apposition, medial canthal angle, and posterofixation of the medial canthus. These results confirmed the long-term value of the operation.

Aged↗

Building a professional environment in long-term care. The role of clinical career development.

1. To be successful, an organizational career development program must include a differentiation of the responsibilities for which the various parties (employer, employee, career counselor) will be held accountable. 2. Project outcomes revealed that the career mobility program was attractive to nursing personnel and facility management personnel alike. However, it was more attractive to nonlicensed than licensed personnel. 3. Of the staff who participated and were promoted, the majority remained in their jobs. The program was most successful in enhancing retention with personnel who received within-level promotions. 4. The process of career development requires collaboration and support from all levels of leadership and staff throughout the organization. A career development program, including a career mobility program with a strong career counseling component, can serve as a catalyst in professionalizing the long-term care work environment.

Career Mobility↗

Toxic agoraphobia.

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Attitude to Health↗

Double valve replacement for lupus valvulitis: report of a case and review of the literature.

Hemodynamically significant lupus valvulitis, requiring valve replacement, is rare: 21 cases have been reported so far in the literature, and only 2 of these have involved double valve replacement. We describe an additional case of double valve replacement in a patient with systemic lupus erythematosus. The histopathologic and clinical features of this case suggest that valvular involvement resulted from both acute and chronic disease processes. Medical success in the treatment of systemic lupus erythematosus, especially that achieved through prolonged or high-dose steroid therapy, may cause chronic valvular disease to become a more common surgical problem. A review of the literature supports this contention.

Journal Article↗

A career mobility program for skilled nursing facilities.

This article reports the results of a 3-year demonstration project in career mobility for nursing personnel in skilled nursing facilities. The goal of the project was to demonstrate the effectiveness of a career mobility program in addressing service delivery challenges such as recruitment, retention, and satisfaction of nursing personnel in skilled nursing facilities. The project was a joint effort between an educational department of a large university and a major long-term care corporation. The project evaluation addressed the effectiveness of this career mobility program in attracting and retaining nursing personnel, the satisfaction of nursing personnel with their jobs, and whether the additional training affected the quality of care. Five pilot and three comparison sites were designated in Southern California. Survey, self-report, and interview data were collected at yearly intervals and at the completion of the project. Descriptive statistics and analysis of variance formed the basis for data analysis and interpretation. Overall, the findings suggested that the career mobility program has the potential to retain staff who benefit from a career development program. The career mobility program was a valuable strategy, but its success was only as good as the management team's authority to support the program and emphasize its goals.

California↗

Studies of connective tissue mast cell-mediated cytotoxicity.

Although mast cells have been implicated in mediating antitumor activity, the kinetics, mechanism(s), and suspectibility of different tumors to mast cell-mediated cytotoxicity have not been defined. Rat connective tissue mast cells (CTMC) of greater than or equal to 99% purity were investigated in vitro and found to express maximal spontaneous cytotoxicity against the mouse fibrosarcoma cell line WEHI-164 (56.0% +/- 2.1 SEM), the ultraviolet B (UVB)-induced, cutaneous fibrosarcoma 5C25 (34.7% +/- 3.4 SEM), and the human renal cell tumor Currie (26.8% +/- 2.0 SEM) at an effector to target (E:T) ratio of 80:1. Kinetic studies of CTMC-mediated cytotoxicity demonstrated significant detectable lysis against these tumors within 8 h, which was maximal by 16 h. Binding experiments showed that CTMC formed conjugates with all three lytic-sensitive targets; however, CTMC also attached to the lytic-resistant target YAC-1, indicating that conjugate formation alone is not sufficient for mast cell-mediated cytotoxicity. At two different concentrations, mast cell granules (MCG) lysed WEHI-164 (36.5% +/- 6.8 SEM) and 5C25 (34.4% +/- 6.9 SEM), but were only slightly cytotoxic (5.7% +/- 2.9 SEM) against Currie. A potential role for tumor necrosis factor-alpha (TNF-alpha) in CTMC-mediated cytotoxicity also was investigated. Polyclonal antibodies to TNF-alpha greatly reduced CTMC and TNF-mediated lysis of WEHI-164, but only partially inhibited CTMC killing of the slightly TNF-sensitive 5C25 tumors, and had no effect on CTMC cytolysis of Currie. Thus, this study demonstrates that CTMC mediate cytotoxicity in vitro by both TNF-associated and TNF-independent mechanisms. We conclude that CTMC are capable of mediating antitumor activity and that this effect may be important for tumor surveillance in the skin and other sites.

Cell Line↗

The intertrochanteric hip fracture. A retrospective analysis.

One hundred intertrochanteric hip fractures were analyzed utilizing a computer-assisted digitization system to study the factors affecting postoperative stability. Fractures were evaluated by measuring shortening and angulation, collapse of telescoping device when utilized, and migration of the fixation device within the femoral head. Fractures were classified preoperatively according to their stability and postoperatively according to the type of operative reduction performed. The failure rate and postoperative stability were then compared according to the type of fracture, type of operative reduction, and internal fixation device utilized. Results indicate that the preoperative fracture classification is a strong and significant determinant of postoperative stability. Conversely, the type of operative reduction was not as significant a determinant of postoperative stability. In particular, medial displacement osteotomy had no advantage over anatomic reduction in the unstable fracture. The use of a fixed angle nail plate was associated with an increased failure rate.

Adolescent↗

Quantitative comparisons of pharmacokinetic drug interactions: a probabilistic approach.

An empirically-based approach which permits the comparison of changes in plasma clearance caused by pharmacokinetic drug-interactions is described. The analysis is based on the calculation of simple probability ratios for defined ranges of clearance changes that are caused by one of the interacting drugs. Examples of drugs increasing the clearance of a second drug through enzyme induction and of drugs decreasing the clearance of a second drug through enzyme inhibition are given. Data for each pair of interacting drugs is empirically fitted using either exponential or logarithmic functions. For each type of interaction a family of curves is generated which permits quantitative comparisons of both the extent and frequency of changes in plasma clearance caused by the interaction.

Drug Interactions↗

Antigen-induced changes in phospholipid metabolism in antigen-binding B lymphocytes.

Previous studies have demonstrated a marked change in the metabolism of phospholipids (PL) after activation of resting B lymphocytes with anti-immunoglobulin (anti-Ig). In this study we examined PL metabolism in highly purified trinitrophenyl (TNP)-binding B cells after their activation with various forms of TNP-carrier protein. Such cells show similar changes in PL metabolism when stimulated with either antigen or anti-Ig, i.e., increased incorporation of 32PO4 into phosphatidic acid and phosphatidyl inositol (PI) but not phosphatidyl choline, phosphatidyl ethanolamine, or phosphatidyl serine. We have demonstrated that these responses to antigen are TNP-specific and dose-related between 1 and 50 micrograms/ml, producing up to a 2.5-fold stimulation of 32PO4 incorporation into PI. The PL response is also directly related to the density of TNP on the carrier and can be augmented by additional cross-linking of the carrier protein. These data suggest that cross-linking of surface Ig by antigen induces a change in PL metabolism as an early event in B cell activation.

Animals↗

Studies of human IgE to a sulfonamide determinant.

We tested the hypothesis that patients who experience immediate hypersensitivity reactions to sulfonamides (SM) express IgE that can bind to a N4-sulfonamidoyl determinant (N4-SM). Sulfamethoxazole (SMX) was coupled to CNBr-activated cellulose disks to form a matrix predominantly substituted with isourea-linked N4-SMX determinants. After incubation of human sera with these disks or bovine serum albumin substituted disks as a control, the binding of IgE was assessed with 125I-labeled antihuman IgE. The binding ratios (counts per minute SMX disks per counts per minute bovine serum albumin disks) for sera from nonallergic donors and newborn infants averaged 1.11 (+/- 0.21 SD). Sera from 10 patients with histories of apparent immediate hypersensitivity reactions to SM were studied. Ratios greater than or equal to 2.1 (greater than 4 SD above control) were detected in 70% (seven of 10). Significant binding was detected in the sera of three of seven patients with other forms of SM allergy. Preincubation with SMX (80 mmol/L) inhibited binding 7% to 35% in eight of the 10 positive sera tested. Binding of one highly reactive serum was significantly inhibited by SMX, sulfamethizole, and sulfamerazine, but not sulfanilic acid or trimethoprim. The results of this study suggest that N4-SM is a major determinant recognized by IgE to SM and that an in vitro assay capable of detecting IgE to SM has been developed.

Adolescent↗