Prevalence and characteristics of brittle diabetes in Britain

We investigated the prevalence and characteristics of 'brittle diabetes', defined as insulin-dependent diabetes mellitus associated with glycaemic instability of any type, leading to life disruption with recurrent and/or prolonged hospitalizations. A questionnaire was sent to all physicians and paediatricians running diabetic clinics in the UK, from lists held at the British Diabetic Association. A total of 414 brittle patients were reported (72% questionnaire return). Most were young (mean age +/- SD was 26 +/- 15 years), though there was a small peak at ages 60-70 years. There was an excess of females (66%) and overall clinic prevalence was 1.2 per 1000 diabetic patients and 2.9 per 1000 insulin-treated diabetic patients. On average, there was 1.0 brittle patient per diabetic clinic. The most common form of brittleness was recurrent ketoacidosis (59%), with 17% having predominant hypoglycaemia, and 24% mixed instability. Female excess was highest and mean age lowest in the recurrent ketoacidosis group, whilst the reverse was true for those with recurrent hypoglycaemia. Causes of brittleness were offered by 58% of consultants, and most (93%) considered various psychosocial problems as likely underlying factors. We conclude that brittle diabetes is a small but significant problem, currently affecting about 1 per 1000 diabetic patients. Most, but by no means all, are young females--often with recurrent ketoacidosis. Older age groups are more likely to have recurrent hypoglycaemic or mixed types of brittleness. Perceived causes of brittleness are usually psychosocial.      

Hepatitis C virus-related autoimmunity in patients with porphyria cutanea tarda

Abstract. Hepatitis C virus (HCV) infection is frequently found in autoimmune hepatitis and mixed cryoglobulinaemia. In these conditions HCV could be responsible for immuno-mediated organ alterations. The aim of this study was to evaluate the presence of immunological alterations in PCT patients, in which HCV infection has been frequently found. Twenty-three PCT patients were evaluated for clinical and serological alterations, including: chronic hepatitis, other systemic symptoms, serum cryoglobulins and rheumatoid factor (RF), haemolytic complement, serum immunoglobulins, anti-nuclear (ANA), anti-smooth muscle (ASMA), anti-liver-kidney-microso-mal (anti-LKMl), anti-soluble-liver-antigen (SLA), anti-mitochondrial (AMA), anti-GOR antibodies, anti-HCV and HCV RNA. Abnormal serum ALT were present in the majority of cases (20/23, 87%), while liver biopsy revealed a chronic persistent hepatitis or chronic active hepatitis in 15/20 (75%) PCT patients. In a high percentage of subjects (91%) the presence of anti-HCV was detected by ELISA and RIBA II (Chiron, Emeryville CA, USA). In 17/22 (77%) cases the ongoing HCV replication in the serum was demonstrated by the detection of HCV genomes (polymerase chain reaction). The prevalence of both anti-HCV and HCV RNA in PCT was significantly higher if compared to 22 systemic immunological diseases ( P< 0.00l) and 47 healthy subjects ( P<0.001 ). A possible HCV-induced autoimmunity in PCT was suggested by the presence of the following immunological parameter alterations: anti-GOR in 13/23 (57%), ANA in 4/23 (17%), ASMA in 18/23 (78%), anti-LKMI in 1/23 (4%), RFin 23/23 (100%), mixed cryoglobulins in 4/23 (170/0), complement consumption in 10/23 (43%). The high prevalence of HCV infection and various immunological abnormalities suggest that HCV in combination with other factors (genetic, alcohol, etc.) could play a relevant role in the pathogenesis of hepatic and metabolic alterations of PCT.     

Long-Term Results of Hybrid Therapy in Patients with Atrial Fibrillation Who Develop Atrial Flutter During Flecainide Infusion

The flecainide infusion test has been proposed to screen candidates for hybrid pharmacological and ablation therapy. We report the long-term follow-up of 154 consecutive patients with paroxysmal or persistent atrial fibrillation (AF) who developed atrial flutter (AFL) during flecainide infusion (IC AFL), treated with inferior vena cava-tricuspid annulus isthmus catheter ablation and oral flecainide (hybrid therapy). Over a mean of 54.1 ± 13.1 months 82 patients (53%) remained free of AF and AFL. Flecainide was discontinued because of adverse effects in 6 patients (4%). A history of persistent AF, and the documentation of ≥1 spontaneous AFL episode before the flecainide test were independent predictors of successful hybrid therapy. In patients with paroxysmal AF without documented spontaneous AFL, the long-term efficacy of hybrid therapy was 38.5% (P = 0.03). The flecainide infusion test reliably detects candidates for hybrid therapy. The efficacy of this therapy is maintained over the long-term with a high patient compliance.     

Memory B cells at successive stages of differentiation. Affinity maturation and the role of IgD receptors

The following evidence, mainly presented here, suggests that IgD receptors play a crucial role in determining the potential for affinity maturation in memory B cell populations. IgD receptors are present on the first memory B cells to appear after priming. These memory cells give rise to more-mature memory cells that have lost their IgD receptors. The proportions of early (IgD(+)) and mature (IgD(-)) memory cells found in individual donors vary with time, priming conditions, and the availability of T cell help, and both populations frequently coexist for long periods of time. IgD(+) and IgD(-) memory cells carry IgG receptors and give rise to IgG responses with identical isotype representation in adoptive recipients. IgD(+) memory cells, however, always give rise to predominantly low-affinity antibody responses, whereas IgD(-) memory cells consistently generate responses of substantially higher average affinity. This affinity differential is maintained between early and mature memory populations in the same donor and does not appear to be a result of selective differentiation of higher-affinity IgD(+) memory cells into the IgD(-) memory pool. Thus, the selective forces responsible for affinity maturation appear to operate mainly in mature memory cell populations that have already lost IgD receptors; or, stated conversely, little or no selection towards high-affinity memory appears to occur among memory cells that retain IgD receptors. In discussing these findings, we suggest that the IgD receptors themselves are responsible for maintaining early memory populations at a lower average affinity than IgD(-) populations in the same animal. The IgD receptors, we argue, serve to increase the antigen-binding capacity of lower-affinity memory cells so that these cells can survive, expand, and differentiate (to IgD(-)) at antigen concentrations that select against expansion of low- affinity memory cells no longer carrying IgD receptors. Thus, when antigen is limiting, IgD(-) memory populations will be selectively expanded to higher average affinities, whereas coexisting IgD(+) populations will retain their initial affinity profile. This hypothesis suggests that mechanisms that regulate expression and loss of IgD receptors are central to the adaptability of the immune system in its response to invading pathogens. Two related roles can be envisioned for the IgD receptors in this regard. First, they extend the lower boundary of the affinity range of early memory cell populations induced by a given antigenic stimulus and therefore broaden the diversity of responses obtainable from these populations. Secondly, they support the persistence of low-affinity memory populations under conditions where antigen becomes limiting and eventually disappears. These persisting populations then serve as a diversely reactive reservoir from which mature memory populations can be drawn with higher affinities either for the original antigen or, more importantly, for related antigens that the animal may subsequently encounter. Thus the existence of IgD receptors on early memory cells maintains the full range of response diversity despite ongoing selective expansion of (mature) memory populations to produce antibodies with high combining affinities for individual antigens. The flexibility inherent in such an organizational system, we believe, could be expected to account for the evolutionary development of IgD receptors and the regulatory capabilities that support operation of the system.     

Application of biosafety principles in blood establishments

In light of increasing public and employee concern over potential infectious hazards associated with blood and other body fluids, several government agencies (the Food and Drug Administration, the Centers for Disease Control, the Occupational Safety and Health Administration, the Environmental Protection Agency, the Health Care Financing Administration and the National Heart, Lung and Blood Institute) cosponsored a Biosafety Workshop in April 1988. The objective of the workshop was to identify appropriate biosafety practices and standard control procedures to protect workers involved in the collection, storage, and transportation of human blood donations with the least possible disruption of the nation's blood supply. Speakers focused on human immunodeficiency virus (HIV) and hepatitis B virus (HBV); however, the safety principles discussed were considered equally applicable to other known (e.g., non-A, non-B hepatitis and human T-lymphotropic virus type I (HTLV-1) blood-transmitted infections. The resulting consensus included the need for blood establishments to develop and apply thoughtful biosafety programs to address staff training, accident prevention, HBV vaccination, handling spills, managing contaminated waste and transporting blood specimens. There was lack of agreement, however, on the usefulness of gloves during the phlebotomy of healthy blood donors.     

血清视黄醇结合蛋白4在妊娠糖尿病患者中显著升高

探讨中国汉族人群血清视黄醇结合蛋白4(RBP4)水平与妊娠糖尿病的关系.收集2005年7月至2007年12月在瑞金医院妇产科行常规产前检查的孕妇195例(妊娠糖尿病组99例,正常糖耐量组96例),同时收集65例非妊娠期健康育龄期妇女作为对照组,所有受试者均排除急慢性疾病,并统一用酶联免疫法检测血清RBP4水平.与非妊娠正常对照组相比,妊娠期妇女血清RBP4水平均明显升高,妊娠糖尿病患者血清RBP4水平较正常妊娠妇女显著升高[(43.04±1.85对33.84±2.17)ms/L,P<0.01].在妊娠期妇女中,多元逐步回归分析显示,胰岛素抵抗指数(HOMA-IR)和甘油三酯是血清RBP4水平升高的独市危险因素(r2=0.165).本研究结果提示,妊娠期妇女血清RBP4水平较非妊娠妇女显著升高,而与正常孕妇相比,妊娠糖尿病患者血清RBP4水平更高;在妊娠期妇女中胰岛素抵抗和甘油三酯水平与RBP4水平显著正相关.     

Monoclonal antibody fluorescence for routine lymphocyte subpopulation analysis with the Abbott CELL-DYN Sapphire haematology analyser

Using previously described procedures, this study quantified T-cell, T-cell subset, B-cell and NK-cell populations with the CD-Sapphire haematology analyser in a series of patients with mild to moderate lymphocytosis. Lymphocyte counts ranged from 6.0 to 14.9 x 10(9)/l, with 86/97 being <10.0 x 10(9)/l. Immunophenotyping (CD3/CD19/HLA-DR, CD4/CD8 and CD16/CD56 combinations) was performed using EDTA-anticoagulated blood, automated CD-Sapphire analysis and subsequent software processing. Of 35 samples from younger (<12 years) patients, 22 (63%) had nonspecific lymphocyte changes, 4 (11%) showed specific increases in nonreactive T-Helper or T-Suppressor cells, and five showed a reactive T-cell lymphocytosis. The remaining four were classified as 'Transient/Persistent NK-associated (NKa) Expansion' (n = 3) and specific B-cell lymphocytosis (n = 1). For older patients (n = 59), 15 (25%) had an increase (>1.5 x 10(9)/l) in B-cells, and seven investigated for surface immunoglobulin expression were all found to be clonal. The remaining samples were categorized as 'Transient/Persistent NK-associated (NKa) Expansion' (13/59), Reactive Lymphocytosis (5/59), 'Reactive Lymphocytosis or Transient/Persistent NKa Expansion' (8/59), specific T-Helper cell (n = 8) or T-Suppressor cell (n = 3) lymphocytosis, and 'Lymphocytosis of Undetermined Significance' (n = 7). This study has demonstrated the feasibility of applying limited immunophenotyping protocols to the investigation of patients with abnormal lymphocyte counts in routine haematology. By using commercially purchased liquid monoclonal reagents to determine lymphocyte subpopulation profiles, haematology laboratories can provide more definitive information of potential clinical importance.