Gene Probe Analysis in an Informative Family with Multiple Endocrine Neoplasia Syndrome Type 2A (MEN 2A). Improvement in Carrier Risk Estimation

Gene probe analysis of the MEN 2A locus on chromosome 10 hasbeen undertaken using the markers TB10.163, RBP 3 and TB14.34in a large kindred with familial medullary thyroid carcinomas,with or without phaeochromocytomas or primary hyperparathyroidism.A maximum LOD score of 2.97 gave strong evidence of close linkagewith zero recombination. For 12 members of the family so far not known to be affectedby any form of the disease the estimated risk of carrying thegene has been considerably decreased in all but one, whose riskhas been greatly increased.     

Absence of capsular contracture in 319 consecutive augmentation mammaplasties: Dependent drains as a possible factor

Capsular contracture is one of the major complications of augmentation mammaplasty. A review of 638 augmented breasts in 319 consecutive patients who underwent primary augmentation, with an average follow-up of 17.2 months and without a single case of capsular contracture of any degree to date, is presented, along with a discussion of the surgical technique and complications, and an analysis of measures used to prevent capsular contraction. Each patient received a pair of smooth saline-filled implants (Mentor, USA) placed in the submuscular space through an inframammary incision. In all operated breasts, many of the known measures commonly used for capsular contracture prevention were implemented. As well, a dependent drain was used as the final hemostatic step to prevent blood accumulation in the pocket. Leaving a dependent drain in the dissected pocket overnight, as one of the sequence of measures aimed at eliminating blood accumulation, is believed to be a contributing factor in capsular contracture prevention.     

Understanding patient acceptance and refusal of HIV testing in the emergency department

Background  

Despite high rates of patient satisfaction with emergency department (ED) HIV testing, acceptance varies widely. It is thought that patients who decline may be at higher risk for HIV infection, thus we sought to better understand patient acceptance and refusal of ED HIV testing.     

The importance of peripheral immune cells in inflammatory bowel disease.

Background/aims: Inappropriate down regulation of an activated immune system is considered as the main pathogenetic mechanism in inflammatory bowel disease. Migration of circulating cells to a diseased intestine is considered as an important factor in the pathogenesis of inflammatory bowel disease. We aimed to evaluate some features of circulating immune cells in inflammatory bowel disease. Methods: Twenty-two control, 29 Crohn's disease and 17 ulcerative colitis patients were studied. CD2, CD3, CD4, CD8, CD11b, CD11c, CD25, CD45RA, CD45RO, CD54 and HLA DR on the surface of peripheral blood lymphocytes and CD11b, CD11c, CD45RA and CD45RO on the phagocytes were researched with two-color immunofluorescence flow cytometry. Results: The percentages of CD2+ and CD4+ lymphocytes were found significantly reduced in ulcerative colitis. CD3+ and CD8+ lymphocytes in inflammatory bowel disease were higher than in controls. CD45RA+ lymphocytes were found significantly decreased in ulcerative colitis and active Crohn's disease. CD45RO+ lymphocytes and CD45RO+, CD11b+ and CD11c+ phagocytes were significantly increased in Crohn's disease. Conclusions: We demonstrated that there were significant differences between ulcerative colitis and Crohn's disease in the expression of some important surface markers on the peripheral blood immune cells. It seems that circulating CD11b-CD11c and CD45RA-CD45RO expressing phagocytes are important in inflammatory bowel disease and may be useful in distinguishing Crohn's disease from ulcerative colitis. These findings may give us some clues about the immunopathogenesis of inflammatory bowel disease.     

Biallelic neutrophil Na-antigen system is associated with a polymorphism on the phospho-inositol-linked Fc gamma receptor III (CD16)

Neutrophils express two distinct types of receptor for the Fc region of IgG, FcRII and FcRIII, in amounts of 10,000 to 20,000 FcRII (40 Kd) and 100,000 to 200,000 FcRIII (50 to 80 Kd) per neutrophil. We showed that the FcRIII exhibits genetically determined heterogeneity, detectable by differences in electrophoretic mobility with sodium dodecyl sulfate (SDS) as well as by reaction with antibodies against the biallelic neutrophil-specific antigen system NA. FcRIII was precipitated with an FcRIII-specific monoclonal antibody (MoAb) from the neutrophils of 35 donors. NA1NA1 donors expressed an FcRIII with a molecular weight (mol wt) of 50 to 65 Kd, NA1NA2 donors expressed an FcRIII with a mol wt of 50 to 80 Kd, and NA2NA2 donors expressed an FcRIII with a mol wt of 65 to 80 Kd. Statistical analysis showed that the electrophoretic heterogeneity corresponds with the NA polymorphism (k = 1). Sequential immunoprecipitation with a MoAb against NA1 and a MoAb against anti- FcRIII, followed by SDS-polyacrylamide gel electrophoresis (PAGE), showed that NA1-FcRIII is distinct from NA2-FcRIII. Moreover, immunoprecipitation with a MoAb against NA1 yielded a protein of 50 to 65 Kd, and immunoprecipitation with human anti-NA2 sera or an MoAb against NA2 yielded a protein of 65 to 80 Kd. Preincubation of NA1NA2 neutrophils with F(ab')2 fragments of an MoAb against anti-NA1 reduced binding of IgG dimers to these cells with about 50%, whereas it completely prevented binding of the dimers to NA1NA1 neutrophils. Inhibition experiments with the MoAb against NA2 yielded the same results for NA1NA2 cells, whereas binding of IgG dimers to NA2NA2 cells was completely prevented. Thus, the products of both NA alleles bind IgG. Immunoprecipitation from the medium of neutrophils either stimulated with formyl- methionyl-leucyl-phenylalanine (FMLP) or treated with glycosyl-phosphatidyl-inositol-specific phospholipase C (GPI- PLC) showed that both the NA1-FcRIII and the NA2-FcRIII are released from the cell surface, indicating that both forms of FcRIII have some structural features in common. Deglycosylation of FcRIII from homozygous donors yielded material that showed several bands on SDS- PAGE. GPI-PLC treatment of neutrophils indicated that all of this material is phosphatidyl-inositol linked.     

Specificity of autoantibodies in autoimmune thrombocytopenia

In 42 patients with autoimmune thrombocytopenia (AITP) and a positive direct platelet suspension immunofluorescence test (PSIFT), the antigenic specificity of the autoantibodies was studied. Because the autoantibodies were often not detectable in the serum and additional HLA antibodies may disturb the reaction pattern with the platelet panel, we used eluates prepared from the patients' platelets for this study. Thirty-five patients had antibodies equally reactive with normal platelets, irrespective of their antigenic make-up, but not with the platelets from two Glanzmann's disease patients. Absorption and elution experiments in two patients showed that his was probably not due to the presence of a combination of anti-Zwa and anti-Zwb antibodies. Thus, the majority of autoantibodies against platelets seems to be directed against antigenic determinants not present on Glanzmann's disease platelets, but perhaps located on the platelet-membrane glycoproteins IIb and/or IIIa. In ten patients, antibodies of no, or still unknown, specificity were detected. Three of these had additional antibodies not reactive with the platelets of the two Glanzmann patients.     

The frequency of sacroileitis and ankylosing spondylitis in inflammatory bowel disease and HLA-B27 association.

BACKGROUND/AIMS: The aim of this study was to investigate the frequency of sacroileitis and ankylosing spondylitis in inflammatory bowel disease and the relationship between disease activity, joint symptoms and HLA-B27 antigen positivity. METHODS: Sacroiliac joint radiography and three phase bone scanning of 33 ulcerative colitis patients (17 active and 16 in remission) and 29 Crohn's disease patients (15 active and 14 in remission) was performed. HLA-B27 was determined in all patients and 60 control subjects. RESULTS: Sacroileitis was found in 10 out of 33 patients with ulcerative colitis (30. 30%) and seven out of 29 patients with Crohn's disease (24. 13%). Of these patients, eleven had active (17.73%) disease and six were in remission (9. 68%). The diagnosis of sacroileitis was made by bone radiography in seven patients (41.18%) and by bone scanning in the other 10 patients (58.82%). A diagnosis of ankylosing spondylitis was made in three patients (17. 64%) who had previously been diagnosed by bone radiography to have sacroileitis. HLA-B27 was positive in six patients (9.67%) with inflammatory bowel disease and three subjects (5%) of the control group. There were no significant differences between these two groups (p>0.05). Compared to the control group, all three patients with ankylosing spondylitis were HLA-B27 positive, the difference being significant (p>0. 01). CONCLUSIONS: The clinical course of sacroileitis is independent of the activitiy of inflammatory bowel disease. Accordingly, patients with inflammatory bowel disease, especially those with sacroileitis, should be investigated for the presence of anklylosing spondylitis.     

Relationship of the clinical response and binding of recombinant interferon alpha in patients with lymphoproliferative diseases

Patients with hairy cell leukemia (HCL) and chronic lymphocytic leukemia (CLL) were treated with recombinant interferon alpha A (rIFN- alpha A). The binding of iodinated recombinant interferon-alpha to baseline samples of peripheral blood mononuclear cells (PBMCs) from the leukemia patients was compared with clinical responsiveness to rIFN- alpha A. HCL patients (8/10) responded to rIFN-alpha A therapy, whereas none (0/10) of the CLL patients studied responded. The PBMCs from the eight responsive HCL patients bound approximately twice as much iodinated interferon as the PBMCs from nonresponsive CLL patients. This difference was due to more high-affinity receptors per cell with no difference in the affinity of the interferon-receptor interaction. However, because PBMCs from HCL patients were larger than PBMCs from CLL patients, the cell surface receptor density was similar. The leukemic cells from one of the two nonresponsive HCL patients bound iodinated interferon similarly to the cells from the responsive HCL patients, whereas the leukemic cells from the other nonresponsive HCL patient bound considerably less. The rapidity of response of the HCL patients did not correlate with the level of binding of iodinated interferon. Our results suggest that the absolute number of interferon receptors per cell may be only one of several important parameters in the response to rIFN-alpha A therapy, and that the responsiveness of a particular lymphoproliferative disease or a particular patient to rIFN- alpha A therapy cannot be predicted or explained solely by the degree of interaction between IFN and its cell surface receptor.