John B. Ziegler

The Faces Pain Scale for the self-assessment of the severity of pain experienced by children: development, initial validation, and preliminary investigation for ratio scale properties.

&NA; Altogether 553 children (195 first graders, mean age 6.8 years, and 358 third graders, mean age 8.7 years) participated in the development of a self‐report measure to assess the intensity of childrens pain. The first step was the derivation, from childrens drawings of facial expressions of pain, of 5 sets of 7 schematic faces depicting changes in severity of expressed pain from no pain to the most pain possible. With the set of faces that achieved the highest agreement in pain ordering, additional studies were conducted to determine whether the set had the properties of a scale. In one study, children rank‐ordered the faces on 2 occasions, separated by 1 week. All 7 faces were correctly ranked by 64% (retest 1 week later, 61%) of grade 1 children and by 86% (retest 89%) of grade 3 children. In a second study, the faces were presented in all possible paired combinations. All 7 faces were correctly placed by 62% (retest 86%) of the younger and by 75% (retest 71%) of the older subjects. A third study asked children to place faces along scale: a procedure allowing a check on the equality of intervals. The fourth study checked on whether pain was acting as an underlying construct for ordering the faces in memory. We asked whether children perceived the set as a scale by asking if memory for an ordered set of faces was more accurate than for a random set. The final study checked, with 6‐year‐old children, the test‐retest reliability of ratings for recalled experiences of pain. Overall, the faces pain scale incorporates conventions used by children, has achieved strong agreement in the rank ordering of pain, has indications that the intervals are close to equal, and is treated by children as a scale. The test‐retest data suggest that it may prove to be a reliable index over time of self‐reported pain.

Postnatal transmission of AIDS-associated retrovirus from mother to infant.

The third child of a previously healthy woman was delivered by caesarean section. Because of intraoperative blood loss, a blood transfusion was given after the delivery. The baby was breast-fed for 6 weeks. One unit of blood came from a male in whom the acquired immunodeficiency syndrome (AIDS) developed 13 months later. On recall, the mother proved to have lymphadenopathy, serum antibody to the AIDS virus, and a reduced T4/T8 ratio. The infant, who failed two thrive and had atopic eczema from 3 months, has likewise proved to have antibody to the AIDS virus. Since his mother was transfused after his birth, he is presumed to have been infected via breast milk or by way of some other form of close contact with his mother.

An investigation of the placebo effect and age-related factors in the report of needle pain from venipuncture in children

Abstract To examine the potential role for a placebo cream in reducing reported needle pain severity in children, and the impact of age‐related factors on pain self‐report, a convenience sample of 117 children scheduled for venipuncture were randomly assigned to one of three treatments: (a) placebo cream with the suggestion that it might help reduce needle pain, (b) placebo cream with no indication as to the creams purpose, and (c) no cream (control group). In allocation to treatment, children were stratified by age group, (3–7, 8–11, 12–17 years). They rated their needle pain severity (both predicted and reported) using the Faces Pain Scale, and rated their anxiety about the procedure using the Childrens Anxiety and Pain Scale. Children in the cream groups were also asked whether they thought the cream had helped. Using video‐tapes, an independent observer, blind to the placebo manipulation, rated each childs reaction to the needle. For the two groups receiving cream, 83% of those children told it might help stated that they believed it did, as compared with only 33% of children who received the cream but were told nothing of its purpose. These beliefs, however, were not reflected in self‐report ratings of pain which showed no statistically significant treatment effect. Similarly, children who gave higher preprocedural anxiety ratings were no more likely to report less pain as a result of receiving the cream. There was, however, a treatment effect on the observers ratings: children receiving cream plus suggestion were assigned significantly lower ratings of pain‐related behaviour than those children who received the cream alone. While venipuncture was associated with only mild levels of pain, younger children, irrespective of treatment group, did report more pain than older children. Hierarchical regression analysis indicated that 60% of the variance in self‐reported pain severity scores could be accounted for by how much the child thought the needle would hurt, how anxious the child was about receiving the needle, gender (higher pain ratings associated with girls), and estimated body surface area (higher pain ratings associated with smaller bodies). We conclude that the efficacy of placebo treatments for needle pain in children may depend on the suggestion of a possible benefit rather than upon treatment application per se.

Vinblastine Therapy for Kaposi's Sarcoma in the Acquired Immunodeficiency Syndrome

Single-agent intravenous vinblastine, 4 to 8 mg/week, was used to treat 38 patients with Kaposis sarcoma related to the acquired immunodeficiency syndrome. The dose was titrated in relation to the total leukocyte count. Ten patients had an objective response, and 19 had stable disease during therapy. Apart from expected modest neutropenia, toxicity was minimal. A lower response rate was seen in patients with anemia, an elevated erythrocyte sedimentation rate, or any lymphoma-like B symptom. Opportunistic infections were common regardless of type of response but were commoner in patients who did not respond. Vinblastine used in low doses weekly is effective in treating Kaposis sarcoma related to the acquired immunodeficiency syndrome and has minimal associated toxicities.

A Multidisciplinary Approach to Non-Hodgkin's Lymphomas

Abstract Epidemiologic studies show that non-Hodgkins lymphomas tend to develop after prolonged antigenic stimulation, after loss of normal regulation of lymphoid proliferation, or especially afte...

Prognostic factors in Burkitt's lymphoma importance of total tumor burden

In 42 patients with African Burkitts lymphoma, we have studied biochemical and clinical correlations with prognosis. Clinical stage and anti‐EA titer were the best predictive factors, but lactic dehydrogenase (LDH) and uric acid (UA) concentrations also correlated with stage and prognosis, whereas lactic acid (LA), which was significantly elevated in Stage D, did not significantly correlate with prognosis or with LDH and UA levels. All of these factors with the possible exception of LA reflect the total body burden of tumor. We conclude that the tumor burden is the single most important prognostic factor in Burkitts lymphoma, and that this is reflected directly by LDH and UA concentrations, and probably indirectly by anti‐EA titer.

IL-21 is the primary common γ chain-binding cytokine required for human B-cell differentiation in vivo

SCID resulting from mutations in IL2RG or JAK3 is characterized by lack of T and natural killer cells; B cells are present in normal number, but antibody responses are defective. Hematopoietic cell transplantation (HCT) is curative for SCID. However, B-cell dysfunction persists in a substantial proportion of patients. We hypothesized that impaired B-cell responses after HCT in IL2RG/JAK3 deficiency results from poor donor B-cell engraftment and defective γc-dependent cytokine signaling in host B cells. To test this, and to identify which γc cytokine(s) is critical for humoral immunity, we studied 28 transplanted patients with IL2RG/JAK3 deficiency. Lack of donor B-cell engraftment associated with persistent humoral dysfunction and significantly reduced memory B cells. B-cell proliferation induced by CD40L alone or together with CpG, anti-Ig, IL-4, IL-10, or IL-13 was comparable in healthy controls and in post-HCT SCID patients, irrespective of their chimerism status. However, in vitro stimulation with CD40L/IL-21 induced B-cell proliferation, plasmablast differentiation, and antibody secretion in patients with donor B cells, but not in patients with autologous B cells. These data imply that IL-21-mediated signaling is critical for long-lived humoral immunity and to restore antibody responses in IL2RG/JAK3-deficient patients after HCT. Furthermore, in vitro stimulation with CD40L/IL-21 can predict in vivo B-cell immunity in IL2RG/JAK3 SCID after transplantation.

Prediction of anaphylaxis during peanut food challenge: usefulness of the peanut skin prick test (SPT) and specific IgE level

Wainstein BK, Studdert J, Ziegler, M, Ziegler JB. Prediction of anaphylaxis during peanut food challenge: usefulness of the peanut skin prick test (SPT) and specific IgE level.
Pediatr Allergy Immunol 2010: 21: 603–611.
© 2010 John Wiley & Sons A/S

Delayed Cutaneous Hypersensitivity Reactions to Autologous Extracts of Burkitt-Lymphoma Cells

Abstract Investigations were performed to determine whether patients with Burkitts lymphoma have delayed hypersensitivity reactions to antigens on the autologous tumor cells. Twelve patients were skin tested two to four days after initial biopsy. Only one patient, with a localized jaw tumor, had a positive reaction to autologous tumor extract, and none reacted to autologous lymphocyte extract. Eight of these patients were retested after treatment, and four additional patients were tested for the first time, when in clinical remission; seven of the 12 had positive reactions to autologous tumor extract. All seven remained in sustained clinical remission, for a median of 31 weeks after therapy. Four of the patients with negative reactions relapsed 14 to 20 weeks after therapy. The results indicate that many patients with Burkitts lymphoma have delayed hypersensitivity responses to autologous tumor antigens and that positive reactions are correlated with sustained remission.

Monogenic mutations differentially affect the quantity and quality of T follicular helper cells in patients with human primary immunodeficiencies

BACKGROUND Follicular helper T (TFH) cells underpin T cell-dependent humoral immunity and the success of most vaccines. TFH cells also contribute to human immune disorders, such as autoimmunity, immunodeficiency, and malignancy. Understanding the molecular requirements for the generation and function of TFH cells will provide strategies for targeting these cells to modulate their behavior in the setting of these immunologic abnormalities. OBJECTIVE We sought to determine the signaling pathways and cellular interactions required for the development and function of TFH cells in human subjects. METHODS Human primary immunodeficiencies (PIDs) resulting from monogenic mutations provide a unique opportunity to assess the requirement for particular molecules in regulating human lymphocyte function. Circulating follicular helper T (cTFH) cell subsets, memory B cells, and serum immunoglobulin levels were quantified and functionally assessed in healthy control subjects, as well as in patients with PIDs resulting from mutations in STAT3, STAT1, TYK2, IL21, IL21R, IL10R, IFNGR1/2, IL12RB1, CD40LG, NEMO, ICOS, or BTK. RESULTS Loss-of-function (LOF) mutations in STAT3, IL10R, CD40LG, NEMO, ICOS, or BTK reduced cTFH cell frequencies. STAT3 and IL21/R LOF and STAT1 gain-of-function mutations skewed cTFH cell differentiation toward a phenotype characterized by overexpression of IFN-γ and programmed death 1. IFN-γ inhibited cTFH cell function in vitro and in vivo, as corroborated by hypergammaglobulinemia in patients with IFNGR1/2, STAT1, and IL12RB1 LOF mutations. CONCLUSION Specific mutations affect the quantity and quality of cTFH cells, highlighting the need to assess TFH cells in patients by using multiple criteria, including phenotype and function. Furthermore, IFN-γ functions in vivo to restrain TFH cell-induced B-cell differentiation. These findings shed new light on TFH cell biology and the integrated signaling pathways required for their generation, maintenance, and effector function and explain the compromised humoral immunity seen in patients with some PIDs.