Gastroesophageal reflux in children with recurrent abdominal pain

In this study we investigated the presence of gastroesophageal reflux in children with recurrent abdominal pain and its possible relationship to food intolerance-associated duodenal inflammation. Twenty-four-hour intra-esophageal pH monitoring, an endoscopic duodenal biopsy and a small bowel 51Cr-EDTA permeability test were performed in 25 children with recurrent abdominal pain. In 14 cases (56%) the pH monitoring was abnormal, pointing to the presence of pathological gastroesophageal reflux. Treatment of gastroesophageal reflux in the latter patients resulted in resolution or improvement of abdominal pain in 10 cases (71%). Gastroesophageal reflux did not appear to be associated with either intestinal permeability to 51Cr-EDTA or duodenal biopsy findings. We conclude that pathological gastroesophageal reflex is a frequent finding in children with recurrent abdominal pain, that it is unrelated to duodenal inflammation and that there might be a causal relationship between pathological gastroesophageal reflux and recurrent abdominal pain in children.     

Pineal tumours in the north of England 1968-93

The records of 38 patients under 25 years of age presenting with pineal tumours between 1968 and 1993, identified from the Northern Region Children's and Young Adults' Malignant Disease Registry, were analysed retrospectively with regards to clinical presentation, diagnostic approach, treatment strategy, and outcome. The overall five year survival was 45%. Fifteen patients had a histological diagnosis: six with germinomas, three with teratomas, three with astrocytomas, and three with pinealoblastomas. One patient had a definitive diagnosis of teratoma made on the basis of raised tumour markers (alpha fetoprotein). Treatment consisted of surgery (87%) (ventriculoperitoneal or atrial shunt and/or biopsy), and/or radiotherapy (82%), and/or chemotherapy (26%). Those patients with a tissue diagnosis appeared to have a more favourable outcome, especially after 1976 when treatment was determined by tumour type (five year survival for those with a tissue diagnosis was 91% v 51% for those without, 95% confidence intervals 74 to 100% and 26 to 75%). This study suggests that tissue diagnosis allows more appropriate treatment to be delivered for children with pineal tumours resulting in improved survival. Referral to a centre with neurosurgery, radiotherapy, neuropathology, and paediatric oncology collaboration is essential.     

Immune response gene function correlates with the expression of an Ia antigen. II. A quantitative deficiency in A(e):E(a), complex expression causes a corresponding defect in antigen-presenting cell function

A series of experiments were performed to explore the role of complementing major histocompatability complex (MHC)-linked immune response Ir genes in the murine T cell proliferative response to the globular protein antigen pigeon cytochrome c. The functional equivalence of I-E-subregion-encoded, structurally homologous E(a) chains from different haplotypes bearing the serologic specificity Ia.7 was demonstrated by the complementation for high responsiveness to pigeon cytochrome c of F(1) hybrids between low responder B 10.A(4R) (I-A (k)) or B 10.S (I-A(8)) mice and four low responder E(a)- bearing haplotypes. Moreover, this Ir gene function correlated directly with both the ability of antigen-pulsed spleen cells from these same F(1) strains to stimulate pigeon cytochrome c-primed T cells from B10.A or B10.S(9R) mice, and with the cell surface expression of the two-chain Ia antigenic complex, A(e):E(a), bearing the conformational or combinatorial determinant recognized by the monoclonal anti-Ia antibody, Y-17. The B 10.PL strain (H-2(u)), which expresses an Ia.7-positive I-E- subregion-encoded E(a) chain, failed to complement with B10.A(4R) or B10.S mice in the response to pigeon cytochrome c. However, (B10.A(4R) × B10.PL)F(1) and (B10.S × B10.PL)F(1) mice do express A(k)(e):E(u)(a) and A(8)(e):E(u)(a) on their cell surface, although in reduced amounts relative to A(k,s)(e):E(k,d,p,r)(a) complexes found in corresponding F(1) strains. This quantitative difference in Ia antigen expression correlated with a difference in the ability to present pigeon cytochrome c to B 10.A and B 10.S(9R) long-term T cell lines. Thus, (B10.A(4R) × B10.PL)F(1) spleen cells required a 10-fold higher antigen dose to induce the same stimulation as (B10.A(4R) × B10.D2)F(1) spleen cells. In addition, the monoclonal antibody, Y-17, which reacts with A(e):E(a) molecules of several strains, had a greater inhibitory effect on the proliferative response to pigeon cytochrome c of B10.A T cells in the presence of (B10.A(4R) X B10.PL)F(1) spleen cells than in the presence of (B10.A(4R) X B10.D2)F(1) spleen cells. These functional data, in concert with the biochemical and serological data in the accompanying report, are consistent with the molecular model for Ir gene complementation in which appropriate two-chain Ia molecules function at the antigen-presenting cell (APC) surface as restriction elements. Moreover, they clearly demonstrate that the magnitude of the T cell proliferative response is a function of both the concentration of nominal antigen and of the amount of Ia antigen expressed on the APC. Finally, the direct correlation of a quantitative deficiency in cell surface expression of an Ia antigen with a corresponding relative defect in antigen-presenting function provides strong independent evidence that the I-region-encoded Ia antigens are the products of the MHC-linked Ir genes.     

In vitro and in vivo persistence of reticulocytes from donor red cells

BACKGROUND: Reticulocytes are important in the phenotyping of transfused patients. Reticulocytes can persist in blood units for the shelf life of the unit. STUDY DESIGN AND METHODS: Temperature dependence of reticulocyte persistence was examined in vitro at 4, 24, and 37 degrees C by using thiazole orange staining and flow cytometric analysis. Two-color flow cytometric analysis was used to evaluate the persistence of donor reticulocytes in transfused patients. RESULTS: Flow cytometric analysis using thiazole orange demonstrated that persistence of reticulocytes in units of stored CPDA-1 blood was temperature-dependent. Reticulocytes disappeared over 13 and 6 days at 24 degrees C and 37 degrees C, respectively, but at 4 degrees C the reticulocyte count changed little over 35 days. Two-color flow cytometric analysis of reticulocyte antigens was used to follow donor reticulocytes in 14 transfusion events in nine different patients. Donor reticulocytes persisted through 24 hours in 75 percent of the patients and were detectable at 48 hours in three patients. CONCLUSION: This study demonstrates that reticulocytes persist during refrigerated storage; they are detectable in the circulation of most recipients for the first 24 hours after transfusion and in the circulation of a few recipients after 48 hours. These findings may have relevance for separation techniques based on reticulocyte density in samples drawn shortly after transfusion and for evaluation of reticulocyte counts in patients with hematologic abnormalities.     

Red cell transfusions in total knee and total hip replacement surgery

To explore how red cell transfusions were used to support patients who underwent primary and revision hip and knee replacements classified within diagnosis-related group (DRG) 209 (major joint and limb reattachment procedures), we studied abstracted patient discharge records from 151 United States hospitals in 1986. A total of 9684 units of whole blood and/or separated red cells was used to support 6472 patients. The transfusion use varied by surgical procedure, with patient gender as an influencing factor. Large proportions of patients underwent surgery without requiring transfusion. Among transfused patients, the majority received 1 to 3 units of red cells; however, a minority of patients required multiple transfusions, thereby utilizing a disproportionate share of the blood resource. Comparison of transfusion practice within the seven most active hospitals revealed significant differences (p less than or equal to 0.01) in the percentage of patients actually transfused, but not in the mean number of units of red cell components transfused per transfused patient. Similar findings emerged from comparison of transfusion practice when all hospitals were segregated into five hospital classes on the basis of orthopedic surgical service activity. These effects were seen for both total knee and total hip replacement procedures. It can be concluded that the lack of clearly defined criteria for transfusion contributed to the variations observed.     

Testing of maternal sera in pregnancies at risk for neonatal alloimmune thrombocytopenia

The utility of prenatal testing of maternal serum for platelet-reactive antibody was assessed in 25 women at risk of delivering infants with neonatal alloimmune thrombocytopenia (NAT). Seventeen women were incompatible with their husbands for the PlA1 antigen and three for Baka; in five families, no demonstrable platelet-specific antigen incompatibility was found. Analysis of the clinical outcome demonstrated that women with platelet-specific antibody detectable in any of the assays at any time during gestation were at risk of delivering thrombocytopenic infants (neonatal platelet count 31,250/microliters if mother did have antibody, as compared with 138,750/microliters if she did not; p less than 0.005). When only PlA1-incompatible pregnancies were examined, this association remained significant (mean neonatal platelet count in infants exposed to anti-PlA1, 34,285/microliters; that in infants not so exposed, 243,000/microliters; p less than 0.001). Changes in antibody strength throughout pregnancy did not correlate with the severity of NAT. The combination of the antigen-capture enzyme-linked immunosorbent assay and the indirect immunofluorescence test appeared to be most sensitive in detecting relevant platelet-specific alloantibodies. It is concluded that the detection of platelet-specific alloantibody in maternal serum in pregnancies at risk for NAT predicts moderate to severe NAT. However, the failure to detect such antibody does not always predict a normal neonatal platelet count.     

A prospective, randomized study of the use of platelet concentrates irradiated with ultraviolet-B light in patients with hematologic malignancy

BACKGROUND: Irradiation of platelet concentrates (PCs) with ultraviolet- B (UVB) light inactivates the contaminating white cells and might be an alternative to filtration for the prevention of alloimmunization to HLA antigens and subsequent refractoriness to further platelet transfusions in multiply transfused patients with bone marrow failure. STUDY DESIGN AND METHODS: Patients with hematologic malignancy, mainly acute myeloid leukemia, were prospectively assigned in a random manner to receive either UVB-irradiated or control, nonirradiated PCs. All patients were given red cells that were white cell reduced by filtration. Transfusion efficacy and alloimmunization were assessed by means of corrected count increments, requirement for red cells and PCs, and measurement of lymphocyte-reactive antibodies. RESULTS: UVB-irradiated PCs had a clinical efficacy similar to controls as judged by corrected count increments at 1 to 6 and 12 to 24 hours and by the median requirement for red cell and platelet transfusions. Alloimmunization determined by measurements of lymphocyte-reactive antibodies using both conventional and antiglobulin-augmented lymphocytotoxicity techniques was not abolished in recipients of UVB-irradiated PCs (4/30, 13%) but was less than that in controls (5/20, 25%; p = NS). The mean number of platelet transfusion episodes prior to the occurrence of alloimmunization was greater in the control group (27 vs. 10; p = 0.017). CONCLUSION: In this trial, UVB irradiation did not diminish the clinical efficacy of platelet transfusions. There was a small but nonsignificant reduction alloimmunization, but no difference in refractoriness of the two groups was observed. Larger prospective randomized studies are required to confirm these findings and to compare UVB irradiation with white cell reduction.