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Biomedical subjects

P F Kohler

Publications and source records attributed to P F Kohler.

At least 19 recordsLinked to original sources

Results of the National Institute of Allergy and Infectious Diseases Collaborative Clinical Trial to test the predictive value of skin testing with major and minor penicillin derivatives in hospitalized adults.

BACKGROUND: A history (or lack thereof) of penicillin allergy is known to be unreliable in predicting reactions on subsequent administration of the drug. This study tests the usefulness of four penicillin allergen skin tests in the prediction of IgE-mediated reactions subsequent to administration of penicillin. METHODS: Eight centers cooperated in the National Institute of Allergy and Infectious Diseases trial of the predictive value of skin testing with major and minor penicillin derivatives. Hospitalized adults were tested with a major determinant (octa-benzylpenicilloyl-ocytalysine) and a minor determinant mixture and its components (potassium benzylpenicillin, benzylpenicilloate, and benzylpenicilloyl-N-propylamine). Patients then received a therapeutic course of penicillin and were observed, for 48 hours, for adverse reactions compatible with an IgE-mediated immediate or accelerated allergy. RESULTS: Among 726 history-positive patients, 566 with negative skin tests received penicillin and only seven (1.2%) had possibly IgE-mediated reactions. Among 600 history-negative patients, 568 with negative skin tests received penicillin and none had a reaction. Only nine of the 167 positive skin test reactors received a penicillin agent and then usually by cautious incremental dosing. Two (22%) of these nine patients had reactions compatible with IgE-mediated immediate or accelerated penicillin allergy; both were positive to the two determinants. CONCLUSIONS: These data corroborate previous data about the negative predictive value of negative skin tests to these materials. The reaction rate in skin test-positive patients was significantly higher than in those with negative skin tests, demonstrating the positive predictive value of positive tests to both major and minor determinants. The number of patients positive only to the major determinant or only to the minor determinant mix was too small to draw conclusions about the positive predictive value of either reagent alone.

Adult

Delayed pressure urticaria histologically resembles cutaneous late-phase reactions.

In a recent study, all patients with delayed pressure urticaria (DPU) developed late cutaneous reaction (LCR) after intradermal injection of compound 48/80 and after skin testing with certain food antigens. In the present study, we analyzed the histologic changes in the pressure lesions and compared them with those found in normal skin injected with diluent and in LCR to 48/80. The study included five patients with DPU associated with chronic urticaria (CU) and four patients with CU but without DPU. Six to eight hours after pressure challenge and intradermal skin testing with 48/80 and diluent, skin biopsy specimens were obtained from the pressure lesions, the LCRs, and normal skin (diluent injection). Specimens were assessed by Giemsa staining of 1-micron sections and immunofluorescence of frozen sections. Total cells were counted in each specimen. Interstitial deposits of fibrin were observed by immunofluorescence in LCR and pressure lesions. The total numbers of infiltrating cells in the dermis among LCR sites and pressure lesions were not significantly different, while both LCR sites and pressure lesions contained significantly more infiltrating cells than did normal skin injected with saline diluent. The differential counts in LCR and DPU were mostly mononuclear cells. Infiltrates in the DPU and LCR were mostly perivascular. No histopathologic changes were seen at skin sites challenged with pressure in the control patients with CU without clinical manifestations of DPU. We conclude that lesions seen in DPU are morphologically similar to classic LCR.

Adult

Lymphocytotoxic antibodies and intermediate immune complexes in hypergammaglobulinemic purpura of Waldenström.

Immune complexes, lymphopenia, and lymphocytotoxic antibodies were detected in two patients with hypergammaglobulinemic purpura of Waldenström. These abnormalities were further characterized in one patient. Ultracentrifugation analysis of this patient's serum showed an intermediate peak likely representing medium sized immune complexes. Circulating IgG-containing immune complexes (2-ME resistant Clq binding material) and IgM rheumatoid factor (2-ME sensitive) were also detected. A sequential study of cold reactive IgM lymphocytotoxic antibodies revealed a significant inverse correlation between antibody levels and peripheral lymphocyte counts. The possible implications of these findings in the pathogenesis of hypergammaglobulinemic purpura are discussed.

Antigen-Antibody Complex

The significance of antilymphocyte antibodies in patients with acquired immune deficiency syndrome (AIDS) and their sexual partners.

Antilymphocyte antibodies have been demonstrated in autoimmune diseases, acute viral infections, and acquired immune deficiency syndrome (AIDS) by using either the conventional microlymphocytotoxicity or the double fluorescence technique. In the present study, we used both methods to detect the antilymphocyte antibodies and to characterize further their immunologic significance in patients with AIDS and their sexual partners. The results using the conventional microlymphocytotoxicity method demonstrated that 8 of 10 patients with AIDS and 6 of 10 partners had significant levels of antilymphocyte antibodies which were reactive with B and T cells at cold and warm temperatures. A significant loss in antibody activity following absorption with B, T, and Daudi cells and Staphylococcus aureus, but not platelets or red cells, indicated that these antibodies are not directed to HLA class I antigens but, rather, to antigens that are common to both groups of lymphocytes. There is a close association between antilymphocyte antibodies and lymphopenia in patients but not in partners. Antibodies against lymphocyte subclasses [helper (T4) and suppressor (T8)] were detected by the double fluorescence staining technique, which employs C6-deficient serum as a nonlytic source of complement, and demonstrated the binding of antibodies to target cells, in contrast to lysing of the target cells as in the microlymphocytotoxicity method. The results of this assay showed that antibodies were directed to both populations, and there was no correlation or association between the absolute numbers of peripheral T4 and T8 cells and the percentage of antibody binding. Taken together, there appear to be at least two kinds of antilymphocyte antibodies: lymphocytotoxic antibodies detected by the conventional microlymphocytotoxicity assay and noncytotoxic antibodies detected by the double fluorescence staining technique. The former may be responsible in part for the lymphopenia. The latter may alter lymphocyte function. The patients and partners who had antilymphocyte antibodies also had anti-HTLV-III antibodies, although there was not any close correlation between titers. These findings support the possibility that both types of antibodies occur as part of a generalized immune response, possibly stimulated by the same viral agent.

Acquired Immunodeficiency Syndrome

Penicillin allergy: a practical approach to management.

Although penicillin is nontoxic, it is highly immunogenic and is the most common drug that causes allergic reactions. A previous reaction to penicillin has been shown to be unreliable in predicting sensitivity in 75% to 90% of patients. To more accurately test for penicillin allergy, diagnostic skin test reagents have been developed; these include the major determinant (benzylpenicilloyl-polylysine) and the minor determinant mixture (penicillin G potassium, benzylpenicilloate sodium and benzylpenicilloyl-N-propylamine). Penicillin skin testing has been shown to be safe and useful in predicting immediate IgE-mediated reactions (overall predictive value 99%). Reactions that occur when patients are challenged with penicillin are mild or accelerated urticarial reactions. We outline a practical and rational therapeutic approach based on the current understanding of penicillin allergy.

Desensitization, Immunologic

Possible role of diet in delayed pressure urticaria--preliminary report.

Late cutaneous reactions preceded by an immediate wheal-and-flare reaction have been described after allergen skin testing, intradermal 48/80 injection, and skin testing with heterologous antihuman IgE. We report the finding of delayed cutaneous reactions after prick food skin testing in a subgroup of five patients with delayed pressure urticaria. This subgroup is also defined by symptomatic clearing after fasting. We demonstrate a correlation of food challenge with skin test response in this same subgroup. Some patients who had previously required prednisone for control of urticaria were able to be managed without it while they were receiving the exclusion diet. In addition, their pressure symptoms and challenge disappeared while they were receiving the restricted diet. These findings suggest that an underlying food sensitivity may be an important precipitating factor in some patients with delayed pressure urticaria.

Adult

Meningococcemia and acquired complement deficiency. Association in patients with hepatic failure.

We treated two patients with severe hepatic failure complicated by meningococcemia. Serum complement profiles performed on these patients found low total hemolytic complement assays, normal concentrations of C1q, and low or undetectable concentrations of C3 through C6, C8, C9, and factors B and I. These studies suggest that these patients developed meningococcemia in the setting of acquired complement deficiency from impaired synthesis of multiple complement system proteins.

Acute Disease

Double fluorescence technique for measurement of complement-fixing antibody to lymphocyte subsets.

A double fluorescent antibody method for quantitating human complement-fixing antibody to lymphocyte subclasses has been developed. The indicators in this system are a C6-deficient serum as a non-lytic source of complement, rhodamine-labeled anti-C3 and fluorescein-labeled murine monoclonal antibodies to human lymphocyte subsets. The basic procedure is to incubate lymphocytes with the unknown serum and then to add C6-deficient serum. The binding of C3 is indicated by staining with rhodamine-labeled anti-C3 and the subset class of the lymphocyte so stained is determined by binding of fluorescein-tagged anti-OKT4 or -OKT8 antibodies. The occurrence of both red and green cell surface fluorescence denotes the presence of a complement-binding antibody to the lymphocyte subset defined by the monoclonal antibody. In addition to defining the specificity of complement-fixing anti-lymphocyte antibodies, this technique is more sensitive than the microcytotoxicity assay.

Acquired Immunodeficiency Syndrome

No demonstrable relationship between IgM and IgG antinuclear antibody levels and acetylator phenotype in patients with systemic lupus erythematosus.

To ascertain the possible influence of acetylator phenotype on antinuclear antibodies in systemic lupus erythematosus (SLE), we assayed sera from 11 rapid acetylators and 10 slow acetylators for IgM and IgG antibodies to chromatin, histones, denatured DNA, and native DNA. Whereas the majority of SLE patients of both acetylator phenotypes had elevated levels of antibodies to all 4 antigens compared with normal controls, there was no difference in antibody activities between slow acetylator patients versus rapid acetylator patients for these antigens. We conclude that levels of antibody to chromatin, histones, and DNA in SLE patients are similar irrespective of acetylator phenotype, and that if a protective effect of slow acetylation on spontaneous development of antinuclear antibodies does occur, a prospective study of presymptomatic individuals at high risk for lupus may be required to reveal this effect.

Acetylation

A quantitative test for xerostomia. The Saxon test, an oral equivalent of the Schirmer test.

We describe a simple, reproducible, and low-cost test for xerostomia, which involves chewing on a folded sterile sponge for 2 minutes. Saliva production is quantitated by weighing the sponge before and after chewing. Normal control subjects produced greater than or equal to 2.75 gm of saliva in 2 minutes. Three of 32 consecutive, unselected outpatients in allergy-immunology clinics and 9 of 38 patients in rheumatology clinics had decreased saliva production, which was significantly different compared with controls (P less than 0.01). The presence of sicca symptoms was highly correlated with quantitatively abnormal tear and saliva production, according to the results of the Saxon and Schirmer's tests.

Adolescent

Susceptibility of Campylobacter isolates to the bactericidal activity of human serum.

Although Campylobacter jejuni and related thermophilic organisms are more common human pathogens than are Campylobacter fetus, most bloodstream or systemic isolates are C. fetus. To understand the pathophysiology related to this observation, the authors studied susceptibility to the bactericidal activity of normal human serum of Campylobacter coli, C. jejuni, and C. fetus isolates from feces and blood. In standardized assays, 10 of 15 C. jejuni and related isolates showed 90% kill (mean, 90.6% +/- 5.9); under more stringent conditions, the relatively resistant strains were completely killed. In contrast, all C. fetus strains were highly serum resistant under both standard and stringent conditions. Killing of C. jejuni was ablated by heating serum to 56 C but restored by addition of complement. Both classical and alternative complement pathways may contribute to killing, and adsorption studies demonstrated antibody dependence. Serum resistance may permit systemic infection by C. fetus, whereas complement- and antibody-mediated serum sensitivity of C. jejuni may account for the relative infrequency of systemic invasion.

Antibodies, Bacterial

Genetic regulation of immunoglobulin and specific antibody levels in twins reared apart.

We studied the effect of the same genetic but different environmental factors on total immunoglobulin and specific antibody levels in twins reared apart. Sera were analyzed from 26 monozygotic (MZ) and 10 dizygotic (DZ) twin pairs, who were separated on average 2 mo after birth and reared apart. Total IgM, IgG, and IgA were measured by single radial diffusion. Specific antibodies of each isotype to tetanus toxoid, and to polyvalent and type 14 pneumococcal capsular polysaccharides were measured by a solid-phase antigen-enzyme-labeled anti-Ig immunoassay. One-way analysis of variance showed intrapair total Ig and antibody levels to be more highly correlated in MZ compared with DZ twins. Our results indicate that genetic factors are more important than environment in regulating these humoral immune responses.

Adult

Episodic angioedema associated with eosinophilia.

We studied four patients with recurrent attacks of angioedema, urticaria, and fever. During attacks, body weights increased up to 18 per cent, and leukocyte counts reached 108,000 per microliter (88 per cent eosinophils). The disease did not appear to threaten the function of vital organs. The two children received prednisone intermittently; the adults did not require treatment or were given alternate-day prednisone. Glucocorticoid therapy caused defervescence and diuresis and decreased total leukocyte and eosinophil counts. No patient had evidence of cardiac involvement (follow-up, 2 to 17 years). One patient remained in spontaneous remission for 20 years before symptoms recurred. Histologic studies showed that eosinophils localized and degranulated in the dermis, and they appeared to induce edema. Although this syndrome might be classified as a variant of the hypereosinophilic syndrome, we believe it is a separate entity because of its distinctive characteristics and its benign course.

Adolescent

Immunohistochemical characterization of the mononuclear cells infiltrating muscle of patients with inflammatory and noninflammatory myopathies.

The immunopathogenetic mechanisms associated with the development of inflammatory myopathies are not well defined. In order to identify cells in affected muscle tissue, mononuclear cells infiltrating muscle biopsies from patients with inflammatory myopathies and controls with other neuromuscular diseases were analyzed in situ by an avidin-biotin immunoperoxidase technique. Serial frozen sections were stained for cells expressing total T, helper-induced T, suppressor-cytotoxic T, B, monocyte/macrophage, and HLA-DR phenotypes. A significant increase in the percentage of helper-inducer T cells are noted in the inflammatory myopathies when compared to the disease control group. Furthermore, most of the mononuclear cells in the inflammatory myopathy biopsies were HLA-DR positive, suggesting that the infiltrating T lymphocytes were activated. No significant differences in mononuclear cell distributions were found when the inflammatory myopathy group was broken down into individual groups of patients with polymyositis, polymyositis with associated connective tissue disease, and dermatomyositis.

B-Lymphocytes

Late cutaneous reactions in patients with delayed pressure urticaria.

Late cutaneous reactions ( LCRs ) have been described in patients after allergen skin testing, skin testing with heterologous anti-human IgE, autologous skin-blister fluid, and, variably, after 48/80 injection. We report our results of skin testing patients with delayed pressure urticaria ( DPU ), chronic urticaria, and normal volunteers with histamine and 48/80. All patients with DPU had LCRs after 48/80. No patients in either of the other groups developed LCRs . This may be a clue to pathogenic mechanisms involved in DPU .

Adult

The hypocomplementemic urticarial-vasculitis syndrome: therapeutic response to hydroxychloroquine.

We report a patient with hypocomplementemic urticarial-vasculitis syndrome. This case illustrates the continuum between urticaria and purpura characteristic of hypocomplementemic urticarial-vasculitis syndrome. Clq precipitin was demonstrated in the patient's serum and in the diethylaminoethylcellulose-ion exchange fraction containing only IgG. A skin biopsy specimen of urticarial and purpuric lesions demonstrated leukocytoclastic vasculitis and granular deposition of C3 and Clq in the basement membrane with IgA, IgM, C3, and Clq in postcapillary venules. Serial total hemolytic complement activity and Clq determinations were performed, and the response to several treatment regimens is presented. Symptomatic and serologic improvement was observed only with hydroxychloroquine.

Adult