Terminal care and survivorship in pediatric chronic illness

Childhood illnesses which were once acutely fatal have slowly yielded to progress in medical science. Some of these illnesses are today chronic life-threatening conditions which pose a new set of psychological challenges. Adaptation to loss and bereavement will still be required of some, but most of the children with these illnesses and their families will be forced to adjust to a new set of psychological realities including a high level of uncertainty. Delineation of the stresses confronting such patients and discussion of appropriate psychological intervention strategies are the heart of this paper. Additional discussion of psychological care during the terminal phase of such illnesses is also included.     

Child health psychology: Emerging responsibilities of the pediatric health psychologist

Child health psychology is an emerging discipline. Emerging, according to Webster's Dictionary, means “to come forth into view; become visible” and “to evolve as something new, improved, etc. ” Both of these definitions aptly describe the current state of child health psychology, and will be used to frame this discussion.As the basis upon which to evaluate the articles which follow, we will describe: 1) the successes of medicine and the resultant context of contemporary medical care that have provided the opportunity and necessity for the development of child health psychology; 2) the knowledge base and responsibilities of the clinical psychologist which are necessary for practice in the health care setting; and 3) the complementary role of the psychological practitioner in the evaluation and management of children with chronic disease.     

Energy transfer-enhanced chromosome banding. An overview

The conditions necessary for energy transfer-enhanced chromosome banding are described and the results of chromosome staining produced by different energy donor-acceptor dye pairs are presented. Energy donors with A-T binding or fluorescence quantum yield specificity, such as 33258 Hoechst or quinacrine, in combination with energy acceptors with G-C specific binding (e.g., actinomycins) produce enhanced Q banding, with especially prominent Q-bright polymorphisms. Conversely, G-C specific energy donors, such as chromomycin A₃ or 7-aminoactinomycin D, when used with methyl green, as an A-T specific energy acceptor, produce a reverse type banding in which different, putative polymorphic regions are highlighted. Donor fluorescence should be insensitive to quenching by the energy acceptor in chromosomal regions compatible with donor binding and fluorescence but not acceptor binding (e.g., clusters of 10–30 A-T or G-C base pairs). In addition to providing information about the molecular basis of chromosome banding and facilitating the detection of certain chromosome polymorphisms, the methodology described may prove useful in characterizing chromosome rearrangements, such as the Philadelphia chromosome (t(9q;22q)) translocation found in chronic myelogenous leukemia.     

Phosphoproteins of vesicular stomatitis virus: identity and interconversion of phosphorylated forms.

Two proteins of vesicular stomatitis virus (VSV), M (matrix) and NS (nucleocapsid-associated), each contained about the same proportion of phosphoserine and phosphothreonine, with phosphoserine as the principal phosphorylated amino acid. Essentially all phosphate (greater than 98%) present in the NS protein was in a typical phosphomonoester bond, while the M protein contained 10 to 15% of its phosphate in an undetermined linkage. Two forms of the NS protein, NS1, and the more highly phosphorylated NS2 form, were separated in SDS-polyacrylamide gels containing urea, and partially digested with chymotrypsin. A comparison of the chymotryptic peptides indicated that the same two phosphorylated forms, NS1 and NS2, were found in virions as well as in the cytoplasm of infected cells. These two forms were interconvertible in vitro. A conversion of NS2 to the lesser phosphorylated NSl form, presumably by a protein phosphatase activity, occurred in the presence of cytoplasm from either infected or uninfected Chinese hamster ovary (CHO) cells. However the amount of the NS1 species was greatly reduced upon acceptance of phosphate through the action of the virion-associated protein kinase. The products of the kinase reaction were analyzed in more detail by matching phosphopeptides from the partial protease digests of the products with NS and M proteins phosphorylated in vivo. In vitro, M protein was the major phosphate acceptor, while in vivo, NS protein had the greatest capacity to accept phosphate.     

EBV transformed B cell lines present to antigen specific T cell clones determinants different from those recognized by antibody in an HLA-DR linked restricted fashion

Human B cells nonspecifically activated by Epstein Barr virus (EBV) can present tetanus toxoid (TT) antigen to TT specific helper T cell lines and T cell clones. Presentation of TT antigen by EBV-B cells did not require the presence of TT specific B cells and did not involve B cell surface immunoglobulins. Immunosorbent purified antibody to TT added in great excess to EBV-B cells pulsed with TT for 18 hr did not inhibit the capacity of the EBV-B cells to present TT antigen. Furthermore, EBV-B cells induced proliferation in T cells in the presence of urea denatured TT which contained less than 1% TT reactive with serum anti TT antibody. Studies of TT presentation by a panel of EBV-B cells obtained from HLA typed donors indicated that T cell recognition of TT presented by EBV-B cells was MHC restricted by products of the HLA-D region and some of which differed from serologically defined HLA-DR. These results indicate that the immunogenic moiety presented by EBV activated human B cells consists of antigenic determinants, which differ from those recognized by serum antibody, and of HLA-DR linked MHC determinants. This moiety is similar to that presented by monocytes. The implications of these findings for the amplification of the immune response by activated B cells are discussed.     

Patterns of late replication in X chromosomes of human lymphoid cells

Two predominant patterns of late X replication were observed in both short-term and established human lymphoid cultures. One pattern was found in a minority of short-term cultured T-cell metaphases, in most lectin-stimulated B cells, and, with minor variations, in established B-cell lines. In these cells, DNA replication terminated in the distal part of the long arm of the late X. A different pattern was found in the majority of lectin-simulated T cells and in the T-cell line CCRF-CEM. These cells exhibited terminal replication in a region of the long arm of the late X that was nearer to the centromere. It is speculated that the variations in replication patterns correlate with phenotypic and functional characteristics of human lymphoid subsets.     

Molecular and cytologic analysis of DNA amplification in retinoblastoma

Amplification of two distinct genomic DNA segments is observed in homogeneously staining regions in two sets of retinoblastoma cell lines derived from two different patients. One DNA segment was known to have sequence homology to the c-myc oncogene, and both DNA segments had previously been shown to be amplified in neuroblastoma cells. The absolute degree of amplification differed in all cytogenetically distinct retinoblastoma cell lines tested. Also, the relative amplification of these two DNA segments was unequal within a given cell line. Minimal amplification of both DNA segments was also detected in DNA directly isolated from one primary retinoblastoma. Based on these and previous results, it is concluded that assembly of amplifiable, relocatable units in many human retinoblastoma and neuroblastoma cells may involve a complex process of differential recruitment of separate DNA segments that are located on human chromosome #2.     

Recombinant avian oncoviruses. II. Alterations in the gag proteins and evidence for intragenic recombination.

The internal structural (gag) proteins of recombinant avian oncoviruses selected for the env gene of RAV-O (an endogenous chicken virus) and the src gene for PR-RSV-C were examined. Eight of ten clones of such recombinants were found to synthesize altered gag proteins. The gag proteins of one recombinant clone, PR-E-95c, were examined in more detail by gel electrophoresis and tryptic peptide mapping. These methods have allowed us to distinguish between the gag proteins of the two parental viruses and to determine from which virus the proteins of the recombinant virus were derived. PR-E-95c virions were found to contain p27₀, an electrophoretically distinguishable variant of p27 which is found in isolates of RAV-0. This recombinant virus also contains p12/15, which is electrophoretically indistinguishable from the p12/15 of both of the parental viruses. However, tryptic peptide analysis of p15 indicates that PR-E-95c has inherited PR-RSV-C-specific p15 sequences. These observations suggest that at least one cross-over has occurred between p15 and p27 in PR-E-95c. A striking difference between the proteins of PR-E-95c virus and those of the parental viruses is that the recombinant lacks polypeptides migrating in the position of p19 and contains two novel polypeptides termed p19α (MW 20,000) and p19β (MW 15,000). Both of these polypeptides are phosphorylated and share antigenic determinants and some tryptic peptides with parental p19. As determined by peptide analysis and radioimmunoassay, these p19-related proteins contain information from both parental viruses, suggesting that PR-E-95c has another cross-over within p19. The altered p19 proteins bind to viral RNA specifically and are associated with genomic RNA in the virion. Neither the stability nor the specific infectivity of the recombinant viruses appears to be significantly affected by the altered proteins.     

Transient hypogammaglobulinemia, elevated immunoglobulin E levels, and food allergy.

Four infants presented with the combination of food allergy, transient hypogammaglobulinemia (THI), and elevated serum IgE levels. Food allergy was documented by history, positive skin tests for immediate hypersensitivity, radioallergosorbent test, histamine release studies, and lymphocyte transformation in response to food allergens. THI was probably secondary to decreased production since there was no evidence of protein loss from the gastrointestinal tract. Immunologic studies revealed normal B cell number and function in vitro. T cell number and proliferative response to mitogens and antigens were normal but T cells were deficient in their ability to generate helper factors necessary for B cell maturation into immunoglobulin secretory cells. The THI and the deficient production of T cell--helper factor resolved after the age of 20 to 24 mo. A defect in immunoregulation may be responsible for the immunologic abnormalities observed in these patients and their propensity to develop IgE antibodies to food allergens.     

Gingival granular cell tumor of the newborn (congenital "epulis"): ultrastructural observations relating to histogenesis

The authors report the electron microscopic features of gingival granular cell tumors (GGCT) resected from two newborn girls. Although origin from odontogenic epithelium has been proposed, the ultrastructural findings strongly support histogenesis from stroma (mesenchymal) cells. Tissue assay for estrogen receptors was negative, but considering the marked predilection of GGCT for females, a hormonal factor (or factors) may still be important in the development of GGCT. Clinical and morphologic features distinguishing GGCT from granular cell "myoblastomas" are briefly emphasized.     

Behavioral treatment of elective mutism: A review of the literature

This paper reviews the behavioral treatment literature concerning elective mutism. Reluctant speech is differentiated from and compared to elective mutism. Twentynine studies were reviewed in terms of treatment strategy, experimental design and clinical outcome. It was concluded that behavioral interventions have advanced the area, but that more rigorous research using single-case methodology is now needed. In order to guide future research, a recommended teratment strategy was offered.     

Specific modulation of complement-dependent human granulocyte function by imidazole acetic acid

Because imidazole acetic acid (IAA), a product of histamine catabolism was shown to inhibit histaminase release from human polymorphonuclear leukocytes (PMNs), the effect of this compound on other neutrophil functions was investigated. IAA at concentrations of 10(-10) or more inhibited histaminase release induced by particle-bound C3b, the larger fragment of the activated form of the third component of complement. Release of histaminase induced by aggregated IgG, phorbal myristate acetate (PMA), formyl-methionyl-leucyl-phenylalanine (FMLP) and calcium ionophore was not affected by IAA. In addition IAA had no effect on release of beta-glucuronidase, myeloperoxidase, and lysozyme or on phagocytosis and superoxide generation. IAA did modestly inhibit neutrophil chemotaxis. These findings suggest a highly specific modulating effect of the histamine catabolite IAA on complement-mediated PMN function.     

Irrational beliefs in the cause and treatment of emotional distress: A critical review of the rational-emotive model

The rational-emotive model of emotional adjustment and psychotherapy (Ellis, 1962) has had a significant impact in clinical psychology during the past two decades. This model has generated a substantial body of research concerning the role of irrational beliefs in the cause and therapeutic alteration of emotional distress. While this body of literature is often cited as supportive evidence for the rational-emotive model, recent criticism of such conclusions have underscored the need for a more critical review of this literature. The present review represents an attempt to critically evaluate the literature concerning the assessment of irrational beliefs, the role of irrational beliefs in causing emotional distress, and the role of irrational beliefs in the treatment of emotional distress. While little disconfirming evidence is found in this literature and a substantial amount of the research findings are consistent with the rational-emotive model, methodological problems and gaps in the literature preclude more than tentative conclusions regarding the model's accuracy. These methodological problems and gaps in existing research as well as suggestions for future research and theory are discussed.     

Differential effects of pharmacologic agents on EAC3 rosette formation by lymphocytes from normal and asthmatic subjects.

We studied the effect of isoproterenol hydrochloride (I) and theophylline (Th) on EAC3 rosette formation by lymphocytes from 30 normal adult subjects, 35 asthmatic subjects, 11 subjects who were age and sex matched with the asthma group, and 10 subjects with allergic rhinitis. Baseline EAC3 rosette numbers were similar for all groups (normal adults, 13.2%; normal children, 15.1%; rhinitis, 14.4%; asthma, 14.6%). Incubation with I and Th in the presence of fetal calf serum caused enchancement of EAC3 rosette formation by lymphocytes from normal adults (mean increase, 52% with I and 53% with Th), from normal age- and sex-matched controls (mean increase, 45% with I and 40% with Th), from subjects with allergic rhinitis (mean increase, 50% with I and 52% with Th), but not by lymphocytes from asthmatic subjects (mean increase, 0% with I and 2% with Th). These results were not affected by bronchodilator therapy. Similar results were obtained with cholera toxin, prostaglandin E₁ and adrenaline, suggesting that the defect in lymphocytes from asthmatic patients resides at the level of 3′, 5′-cyclic adenosine monophosphate (cAMP) production or at the level of cAMP-triggered events. Lymphocyte fractionation experiments into T cell-rich, B cell-rich, and null cell populations revealed that the null cell population was a target for the I-mediated enhancement of EAC3 rosette formation. Null cells from normal subjects, but not from asthmatic subjects, exhibited an increase in the number of EAC3 rosettes formed following incubation with I. This enhancement required protein synthesis as it was prevented by the addition of puromycin hydrochloride. The resistance of peripheral blood lymphocytes from asthmatics to the enhancing effect of I and Th on EAC3 rosette formation may be used to study the biochemical defect in asthma and should be assessed for possible use in the detection of the latent asthmatic.     

Hypersensitivity to pancreatic extracts in parents of patients with cystic fibrosis.

Because immediate hypersensitivity reactions can occur in individuals exposed to powdered pancreatic extracts, 36 patients with cystic fibrosis and 51 patents of such patients wwer studied for evidence of sensitization. Sensitivity to the extracts as evidence by history and skin testing was infrequent in the children with cystic fibrosis. However, skin testing for immediate hypersensitivity with either crude pancreatic extracts or inactivated trypsin correlated well in their patents with a history of clinical symptoms. IgE mediation of these reactions in sensitized individuals was demonstrated by antigen-induced histamine release from leukocytes, passive transfer studies, and immediate response to inhalation challenge.