Pulsatile Basal Insulin Secretion Is Driven by Glycolytic Oscillations.

In fasted and fed states, blood insulin levels are oscillatory. While this phenomenon is well studied at high glucose levels, comparatively little is known about its origin under basal conditions. We propose a possible mechanism for basal insulin oscillations based on oscillations in glycolysis, demonstrated using an established mathematical model. At high glucose, this is superseded by a calcium-dependent mechanism.

An overview of international literature from cystic fibrosis registries: 1. Mortality and survival studies in cystic fibrosis.

Patient registries are organized systems of data collection for scientific, clinical or health strategy purposes. Aims of our review were to document scientific literature based on data and information from cystic fibrosis (CF) registries; to understand which clinical problems have been addressed and for which of these the studies concerned have correctly answered the questions raised (i.e. a methodological critique) and to identify clinical issues in need of further investigation. The review included primary studies starting from a formally constituted CF registry of at least national level, using data from the registry to evaluate research hypotheses. This article is an overview of the research undertaken, focusing in detail on the issues of mortality and survival. The studies considered here focused mainly or secondarily on survival in CF, the aim being to ascertain an improving trend, identify any prognostic factors and, in some cases, attempt to provide a predictive model of survival.

Terapia e evoluçäo do candidato a receptor do transplante cardíaco / Therapy and evolution of the candidate to heart transplantation

As doenças mais comuns que acometem o candidato a transplante cardíaco säo as cardiomiopatias, a doença coronária e, menos frequentemente, a doença cardíaca congênita e a rejeiçäo do enxerto. No Estudo de Framingham, foi demonstrado que a sobrevivência do paciente com insuficiência cardíaca é menor que 50 por cento em cinco anos após o início dos sintomas. Em outros estudos, na insuficiência cardíaca com sintomas avançados a sobrevivência chega a ser de 40 por cento - 60 por cento após um ano. O coecimento da fisiopatologia da insuficiência cardíaca, principalmente dos mecanismos neuro-hormonais e dos fatores prognósticos, tem proporcionado abordagens terapêuticas mais adequadas para melhorar os sintomas, a qualidade de vida e a sobrevivência dese grupo de pacientes. Apesar da melhora na sobrevida, o prognóstico ainda continua pobre; por isso, novas abordagens devem ser encontradas. A abordagem terapêutica de que dispomos no momento serve para retardar a evoluçäo da doença e controlar o paciente oo ponte para o transplante cardíaco.

Lethal short rib syndrome of the Beemer type without polydactyly.

A new case of Beemer short-rib dwarfism is reported and the clinical and radiological differences between this and Majewski type are discussed. The clinical variability related to the lack or presence of polydactyly is underlined, together with the importance of prenatal diagnosis.

[Mitral valve replacement with porcine bioprosthesis in children. Evaluation of 29 patients during 12 years]. / Substituição valvar mitral por bioprótese porcina em crianças. Avaliação de 29 pacientes durante 12 anos.

PURPOSE: To analyze the clinical result of the mitral valve substitution for the porcine bioprostheses, the incidence of dysfunction caused by calcification and its importance related to the durability of bioprostheses and also the patients' survival. METHODS: Twenty-nine children of about seven to sixteen years old were operated on from November 1977 to August 1982 and all of them received porcine bioprostheses of low profile. RESULTS: There were three (10.34%) hospital deaths and nine other late mortalities. The follow-up period varied from 4 to 128 months with average of 58.17 months and with the loss of nine patients. An actuarial survival rate of 46.08% has been observed at 11 years after surgery. Calcification of 21 bioprostheses occurred in 14 out of 17 follow-up patients; 47.6% of them happened until the third year of pos-operative and 85.7% until the fifth year. Eleven patients were reoperated on with 9.09% of hospital mortality. There were no cases of thromboembolism. CONCLUSION: Porcine bioprostheses works well with an evident clinical improvement of patients, with no thromboembolic accidents. However, its durability has been affected by the high incidence of calcification, which is responsible for an increase in late morbidity and mortality. Mitral valve disease treatment in children must be conservative, in an attempt to solve the problem with the different available plastic technics and leave the valve substitution to be a last option. In that case, the preference is given to the homologous bioprostheses.

[Partial agenesis of the musculus pectoralis major]. / Agenesia parziale del muscolo grande pettorale.

The authors report a rare case of partial agenesia of the pectoralis major muscle with presence of the "pars clavicularis" only. Full range of movement was possible in this case, in accordance with other reports in the literature.

Inactive subretinal neovascularization in age-related macular degeneration.

Inactive subretinal new vessels (SRNVs), showing minimal leakage by fluorescein angiography and little progression, were observed in 15 eyes of 12 patients with age-related macular degeneration. In 8 (57%) of 14 eyes followed for longer than 6 months, the new vessels involuted and produced circumscribed areas of retinal pigment epithelium and choriocapillaris atrophy; 6 (43%) showed a further decrease in the fluorescein leakage during the follow-up period (average, 30.1 months). None of the new vessels organized into an exudative fibrovascular scar. Visual acuity was improved or unchanged during the entire follow-up period in 12 (86%) eyes and deteriorated in 2 (14%). Nine patients (75%) were 80 years of age or older; three (25%) were between 65 and 70 years of age. These observations suggested that SRNV showing minimal fluorescein leakage, particularly when it occurs in patients older than 80 years, do not require photocoagulation because they are usually self-limited.

T-cell response to anti-CD2 monoclonal antibodies in Down's syndrome.

Peripheral blood mononuclear cells from 10 subjects with cytogenetically documented Down's syndrome (DS) and from 10 age- and sex-matched healthy controls were assayed for their ability to proliferate in response to phytohaemagglutinin, anti-CD3 (OKT3), or anti-CD2 (T11(2) plus T11(3] monoclonal antibodies. Interleukin 2 (IL-2) receptor expression and IL-2 production in mitogen-pulsed lymphocyte cultures was also investigated in parallel. DS cells responded poorly to all the blastogenic stimuli used in this study. Under certain experimental conditions (anti-CD3 or anti-CD2 antibody stimulation), the patients' lymphocytes expressed low levels of IL-2 surface receptors and failed to produce normal amounts of this lymphokine. Studies are currently in progress in our laboratories to determine whether these defects are due to an impairment of the early signalling events surrounding the complexing of CD3, CD2, or lectin receptors to their respective ligands.

Activation of cord T lymphocytes. I. Evidence for a defective T cell mitogenesis induced through the CD2 molecule.

A study was carried out on cord blood T cell activation via the CD2-mediated pathway. Despite similar percentages of circulating CD3+ and CD2+ cells in adult and cord blood, the proliferation of cord PBMC to the anti-CD3 mAb and cord T cells to anti-CD2 mAb were defective. The T cell CD3-surface structure was normally able to control CD2-mediated activation, as its modulation by a non-mitogenic anti-CD3 mAb blocked cord PBMC proliferation induced by anti-CD2 mAb. CD2-stimulated cord T cells did not proliferate and did not produce a significant amount of IL-2 in culture, although they expressed the IL-2R. This observation was confirmed by the optimal proliferation of CD2-induced cord T cells when rIL-2 was added. Despite the alternative T cell activation pathway is monocyte-independent in adults, the defective cord T cell activation via the CD2 molecule could also be bypassed by the addition of PMA, small amounts of either autologous or allogeneic adult and cord AC or simply rIL-1 alone. Our findings provide evidence for an intrinsic functional defect in cord CD2-mediated T cell activation, which is linked to an impaired increase of free cytoplasmic calcium, as confirmed by the effectiveness of calcium ionophore A23187 in restoring a good CD2-induced cord T cell proliferation and by measurement of cellular calcium uptake after activation via the CD2 molecule. The characteristics of cord T cells revealed by this study recall the thymocyte functional pattern and may represent functional expression of the previously described phenotypic immaturity of cord T cells.

T cell response to anti-CD3 antibody in Down's syndrome.

The non-specific mitogen phytohaemagglutinin (PHA) and an anti-CD3 (OKT3) monoclonal antibody were used to measure the lymphocyte proliferative response in blood samples from 15 subjects with Down's syndrome. Blood from 15 healthy controls closely matched for age and sex was also assayed. The mean blastogenic value in PHA stimulated patient lymphocyte cultures was similar to that calculated in the controls. In contrast, the mitogenic response of lymphocytes from patients with Down's syndrome to anti-CD3 stimulation was on average significantly reduced. Immunofluorescence studies and additional experiments carried out by using semiallogeneic (maternal) monocytes as a source of antigen presenting cells showed that the impaired anti-CD3 induced mitogenesis in Down's syndrome could not be ascribed either to a lack of binding of the antibody to the trisomic cells, or to a defective monocyte-T cell interaction. These findings help to explain the cellular basis of the immune defect in Down's syndrome.

Phenotypic heterogeneity within the circulating human neonatal T4-positive T cell subset.

An indirect immunofluorescence staining technique was employed to evaluate the TQ1 and 5/9 monoclonal antibody lymphocyte reactivity in 10 cord blood mononuclear cell (MC) preparations enriched of E-rosette-forming cells (E+). Ten adult E+ MC populations were used as controls. Unfractionated T4+ cord and adult MC positively selected by panning procedure were also assayed. The results of these experiments, taken together, suggest that there is an overexpanded neonatal T cell subset which displays a previously unrecognized immunophenotype (T4+, TQ1+, 5/9+). Whether these lymphocytes are involved in the wellknown fetal-maternal immunosuppressive mechanisms of whether they are a further example of neonatal phenotypic immaturity remains to be elucidated.