In vivo histamine release during the first minutes after deliberate sting challenges correlates with the severity of allergic symptoms

In this study, deliberate sting challenge was investigated as a method for estimating the severity of anaphylactic reactions in bee venom‐sensitized subjects. Twenty‐one patients with previous anaphylactic reactions to field bee sting were subjected to a deliberate sting challenge (n = 32). To document anaphylactic reactions, plasma histamine levels were measured before, and then 1 and 2 min after, bee sting challenge. Eleven patients were re‐challenged after 3–5 weeks. On 18 occasions, sting challenges caused no systemic reactions, in seven cases reactions were mild, in five moderate and in two severe. In all children showing systemic reactions, significant increases of plasma histamine were measured after 2 min. The results correlated significantly with clinical scores but not with skin prick test or with specific immunoglobulin E (IgE) and immunoglobulin G (IgG) antibodies against bee venom. In patients developing local reactions only, no increase of plasma histamine was detected. The relative amount of released histamine correlated significantly with the severity of clinical symptoms. Significant histamine release occured during the first 2 min after sting challenge in children with subsequent systemic reactions and the severity of these subsequent anaphylactic reactions correlated with plasma histamine concentrations. The measurement of plasma histamine levels in the first minutes after challenge test may therefore be used as an objective marker of a potential systemic reaction.     

Sub-class of IgG in allergic disease. I. IgG sub-class antibodies in immediate and non-immediate food allergy

Previous studies have suggested that, apart from IgE-mediated reactions, some of the symptoms of food allergy may be caused by IgG antibodies to food proteins. This study was carried out to see if there were any distinctive features of the IgG sub-class antibody response to dietary antigens which occurs in food allergic patients. IgG sub-class antibodies were measured using a quantitative enzyme-linked immuno-sorbent assay (ELISA) to wheat gliadin, ovalbumin and bovine casein in twenty patients who had coeliac disease and in twenty-eight egg allergic patients. These were compared with twenty-one atopic dermatitis patients who did not have food allergy and twenty-six healthy control subjects. Coeliac disease patients tended to have raised IgG antibody levels (especially IgG1) to all three antigens but these overlapped considerably with that seen in egg allergic and atopic dermatitis patients. Coeliacs who avoided gluten had anti-gliadin antibody levels which did not differ from those seen in healthy subjects but nevertheless had raised anti-ovalbumin and casein-specific antibodies. The IgG antibody was largely restricted to IgG1 and IgG4 sub-class although the relative amount of each varied with the antigen. Although gliadin-specific antibodies were mainly IgG1, ovalbumin-specific antibodies were mainly IgG4. The increased antibody levels to all three antigens in coeliacs were caused by a raised IgG1 response, IgG4 antibodies were usually normal. Egg allergic patients also had raised IgG1 but not IgG4 antibodies to ovalbumin. These data show that the response to different dietary antigens can vary with the antigen. The fact that IgG1 and not IgG4 antibodies were raised to all three antigens in patients with coeliac disease suggests that they are a secondary consequence of the disease, perhaps reflecting increased transport of antigens across a damaged gut mucosa rather than a specific immunopathological reaction. However, the observation that antibodies to gliadin, and not ovalbumin or casein, fell following gluten avoidance shows that the response to gliadin, at least, is dependent upon continued exposure to antigen.     

Atopy-suggesting symptoms in the first 2 years of life. Effect of gestational age, nutrition and social class

In a prospective study on 318 non-selected infants signs of atopy as well as interrelations with feeding regimens and family history of atopic disease were investigated at the age of 1 1/2 year. The study population was recruited from preterm and term babies hospitalized 1985 in the University Children's Hospital Freiburg, Germany. The most common symptom was eczema. In addition, clinical symptoms of atopy in first degree relatives were a significant risk factor. Because the highest incidence of atopic symptoms occurred in preterm born children with allergic background in their families, we therefore consider this population at highest risk to develop atopic disease. On the other hand there was no significant influence of breast feeding, cow's milk formula and the time of intake of allergenic food on the clinical manifestation of atopy in any group. Although eczema occurred predominantly in infants with higher social level the respiratory tract symptoms were reported more frequently in children from working class families. We therefore regard the social status as an important confounding variable in the studies of risk factors for the development of allergy.     

The Human Heart: A Self‐Renewing Organ

The dogma that the heart is a static organ which contains an irreplaceable population of cardiomyocytes prevailed in the cardiovascular field for the last several decades. However, the recent identification of progenitor cells that give rise to differentiated myocytes has prompted a re‐interpretation of cardiac biology. The heart cannot be viewed any longer as a postmitotic organ characterized by a predetermined number of myocytes that is defined at birth and is preserved throughout life. The myocardium constitutes a dynamic entity in which new young parenchymal cells are formed to substitute old damaged dying myocytes. The regenerative ability of the heart was initially documented with a classic morphometric approach and more recently with the demonstration that DNA synthesis, mitosis, and cytokinesis take place in the newly formed myocytes of the normal and pathologic heart. Importantly, replicating myocytes correspond to the differentiated progeny of cardiac stem cells. These findings point to the possibility of novel therapeutic strategies for the diseased heart.     

Endoscopic incision of the pancreatic duct

Concrements in the prepapillary portion of the Wirsungian duct result in secretion with simultaneous obstruction and, thus, represent a potential cause of pancreatitis. The removal of these concrements is indicated and rendered possible by endoscopic incision of the pancreatic duct. This procedure has been performed only very rarely up to the present. Its efficacy is demonstrated by a case report.     

Myocardial regeneration by activation of multipotent cardiac stem cells in ischemic heart failure

In this study, we tested whether the human heart possesses a cardiac stem cell (CSC) pool that promotes regeneration after infarction. For this purpose, CSC growth and senescence were measured in 20 hearts with acute infarcts, 20 hearts with end-stage postinfarction cardiomyopathy, and 12 control hearts. CSC number increased markedly in acute and, to a lesser extent, in chronic infarcts. CSC growth correlated with the increase in telomerase-competent dividing CSCs from 1.5% in controls to 28% in acute infarcts and 14% in chronic infarcts. The CSC mitotic index increased 29-fold in acute and 14-fold in chronic infarcts. CSCs committed to the myocyte, smooth muscle, and endothelial cell lineages increased approximately 85-fold in acute infarcts and approximately 25-fold in chronic infarcts. However, p16(INK4a)-p53-positive senescent CSCs also increased and were 10%, 18%, and 40% in controls, acute infarcts, and chronic infarcts, respectively. Old CSCs had short telomeres and apoptosis involved 0.3%, 3.8%, and 9.6% of CSCs in controls, acute infarcts, and chronic infarcts, respectively. These variables reduced the number of functionally competent CSCs from approximately 26,000/cm3 of viable myocardium in acute to approximately 7,000/cm3 in chronic infarcts, respectively. In seven acute infarcts, foci of spontaneous myocardial regeneration that did not involve cell fusion were identified. In conclusion, the human heart possesses a CSC compartment, and CSC activation occurs in response to ischemic injury. The loss of functionally competent CSCs in chronic ischemic cardiomyopathy may underlie the progressive functional deterioration and the onset of terminal failure.     

The young mouse heart is composed of myocytes heterogeneous in age and function

The recognition that the adult heart continuously renews its myocyte compartment raises the possibility that the age and lifespan of myocytes does not coincide with the age and lifespan of the organ and organism. If this were the case, myocyte turnover would result at any age in a myocardium composed by a heterogeneous population of parenchymal cells which are structurally integrated but may contribute differently to myocardial performance. To test this hypothesis, left ventricular myocytes were isolated from mice at 3 months of age and the contractile, electrical, and calcium cycling characteristics of these cells were determined together with the expression of the senescence-associated protein p16(INK4a) and telomere length. The heart was characterized by the coexistence of young, aged, and senescent myocytes. Old nonreplicating, p16(INK4a)-positive, hypertrophied myocytes with severe telomeric shortening were present together with young, dividing, p16(INK4a)-negative, small myocytes with long telomeres. A class of myocytes with intermediate properties was also found. Physiologically, evidence was obtained in favor of the critical role that action potential (AP) duration and I(CaL) play in potentiating Ca(2+) cycling and the mechanical behavior of young myocytes or in decreasing Ca(2+) transients and the performance of senescent hypertrophied cells. The characteristics of the AP appeared to be modulated by the transient outward K(+) current I(to) which was influenced by the different expression of the K(+) channels subunits. Collectively, these observations at the physiological and structural cellular level document that by necessity the heart has to constantly repopulate its myocyte compartment to replace senescent poorly contracting myocytes with younger more efficient cells. Thus, cardiac homeostasis and myocyte turnover regulate cardiac function.     

Identification of a polycystic ovary syndrome susceptibility variant in fibrillin-3 and association with a metabolic phenotype

CONTEXT: Polycystic ovary syndrome (PCOS), the most common reproductive endocrine disorder of premenopausal women, is also associated with metabolic abnormalities including insulin resistance and an increased risk for diabetes mellitus. We previously mapped a PCOS susceptibility locus to chromosome 19p13.2 near the dinucleotide repeat marker D19S884. OBJECTIVE: Our objective is to localize the chromosome 19p13.2 PCOS susceptibility locus and determine its impact on metabolic features of PCOS. DESIGN: Resequencing and family-based association testing were used to examine the effect of sequence variation within 100 kb of D19S884 on the reproductive and metabolic phenotypes of PCOS. SETTING: The study was conducted in an academic medical center. SUBJECTS: Genetic analyses were performed on DNA obtained from1723 individuals in 412 families with 412 index cases and 43 affected sisters of predominantly European origin (>94%). Genotype-phenotype associations were assessed in 601 women with PCOS and 168 brothers of affected women. RESULTS: D19S884 allele 8 (A8) within intron 55 of the fibrillin-3 (FBN3) gene showed the strongest evidence for association with PCOS of 53 variants tested (P(corrected) = 0.0037). A8 was also associated with higher levels of fasting insulin and homeostasis model assessment for insulin resistance in women with PCOS and higher fasting levels of proinsulin and proinsulin/insulin ratio in brothers. CONCLUSIONS: These findings strongly suggest that A8 of D19S884 is the chromosome 19p13.2 PCOS susceptibility locus. The association of D19S884 with markers of insulin resistance and pancreatic beta-cell dysfunction suggests that the same variant contributes to the reproductive and metabolic abnormalities of PCOS in affected women and their brothers.     

Coronary venoplasty during the implantation of the cardiac resynchronisation device--a case report

We describe a case of a 76-year-old patient with advanced block in the His-Purkjnie system, who underwent implantation of a cardioverter-defibrillator with cardiac resynchronisation therapy. Complete heart block occurred during the insertion of the coronary sinus cathether. The implantation of the left ventricular (LV) lead was impossible due to difficult anatomy of the coronary venous system. The right ventricular pacing caused the further prolongation of the QRS duration and exacerbation of heart failure symptoms. Thus, the LV lead was successfully implanted during the second procedure after the balloon venoplasty of the lateral cardiac vein. The biventricular pacing was successful during 4 months follow-up.