Ketoacidosis at the diagnosis of type 1 (insulin dependent) diabetes mellitus is related to poor residual beta cell function. Childhood Diabetes in Finland Study Group

The determinants of the degree of metabolic decompensation at the diagnosis of type 1 (insulin dependent) diabetes mellitus (IDDM) and the possible role of diabetic ketoacidosis in the preservation and recovery of residual beta cell function were examined in 745 Finnish children and adolescents. Children younger than 2 years or older than 10 years of age were found to be more susceptible to diabetic ketoacidosis than children between 2 and 10 years of age (< 2 years: 53.3%; 2-10 years: 16.9%; > 10 years: 33.3%). Children from families with poor parental educational level had ketoacidosis more often than those from families with high parental educational level (24.4% v 16.9%). A serum C peptide concentration of 0.10 nmol/l or more was associated with a favourable metabolic situation. Low serum C peptide concentrations, high requirement of exogenous insulin, low prevalence of remission, and high glycated haemoglobin concentrations were observed during the follow up in the group of probands having diabetic ketoacidosis at the diagnosis of IDDM. Thus diabetic ketoacidosis at diagnosis is related to a decreased capacity for beta cell recovery after the clinical manifestation of IDDM in children.     

Standards for total body fat and fat-free mass in infants

Data on body composition in conjunction with reference centiles are helpful in identifying the severity of growth and nutritional disorders in infancy and for evaluating the adequacy of treatment given during this important period of rapid growth. Total body fat (TBF) and fat-free mass (FFM) were estimated from total body electrical conductivity (TBEC) measurements in 423 healthy term Caucasian infants, aged 14-379 days. Cross sectional age, weight, and length related centile standards are presented for TBF and FFM. Centiles were calculated using Altman's method, based on polynomial regression and modelling of the residual variation. The TBF percentage steeply increased during the first half year of life, and slowly declined beyond this age. Various simple TBEC derived anthropometric prediction equations for TBF and FFM are available to be used in conjunction with these standards. Regression equations for the P50 and the residual SD, depending on age, weight, or length, are provided for constructing centile charts and calculating standard deviation scores.     

STUDY OF PERIPAPILLRY NERVE FIBER LAYER MEASUREMENT BY SCANNING LASER POLARIMETRY BETWEEN EYES OF GLAUCOMA SUSPECTS AND THOSE WITH GLAUCOMATOUS VISUAL FIELD DEFECT

Interpretation of quantitative results of nerve fiber layer (NFL) thickness based on scanning laser polarimetry (GDx-NFA) can be quite challenging especially in glaucoma suspects. Purpose: Authors studied NFL parameters obtained from GDx-NFA in glaucoma suspects and compared them with those of patients with glaucoma Methods: Eighty six glaucoma suspects based on     

Differential effects of nongenotoxic and genotoxic carcinogens on the preneoplastic lesions in the rat liver

GlutathioneS-transferase placental form (GST-P) positive foci development and its expression in liver exposed by nongenotoxic carcinogens phenobarbital (PB) and clofibrate (CF), and genotoxic carcinogen 2-amino-3-methylimidazo[4,5-f] quinoline (IQ) were investigated as a measure of carcinogenic potential of these chemicals. Male F344 rats were initially given a single intraperitioneal injection of diethylnitrosamine (200 mg/kg), and 2 weeks later, animals were fed diets containing 0.03% IQ or 0.5% CF or 0.05% PB or basal diet as a control for 6 weeks. All rats were subjected to two-thirds partial hepatectomy (PH) at week 3. Sequential sacrifice of rats was performed at 8 weeks or 52 weeks, and liver tissues were examined for immunohistochemical staining of GST-P positive foci. The numbers (No./cm²) and areas (mm²/cm²) of GST-P positive foci were increased by IQ or PB, but were decreased by CF compare to the control. Consistent with the development of GST-P positive foci, a time-related increase in the expression of GST-P mRNA was found in the rats treated with IQ, whereas CF decreased it. The incidence of hepatocellular carcinoma at 52 weeks was increased by all three chemicals. These results show that PB and IQ induced GST-P positive foci, but the peroxisome proliferator CF did not, which suggest that the prediction of carcinogenic potency based on the development of prenoplastic foci may cause false negative in a particular category compounds like peroxisome proliferators.     

Hormone-like activity of a thymus humoral factor on the induction of immune competence in lymphoid cells

Experiments reported here were performed to understand the mechanism by which THF increases the immunocompetence of spleen cells from NTx mice. Dibutyryl cAMP or substances which increase intracellular levels of cAMP in lymphocytes such as Poly(A:U), theophylline, or PGE₂ were shown to mimic the effect of THF and confer reactivity in an in vitro GvH response to spleen cells from NTx mice. Flufenamic acid, an antagonist to PGE₂, was shown to inhibit the induction of competence by this substance. It was found that THF induces competence by activating membranal adenyl cyclase which leads to a rise in intracellular cAMP in thymus-derived cells only. These biochemical changes occur before antigenic stimulation and are unrelated to antigenic challenge. These findings indicate that THF exerts its effect via cAMP and are in agreement with the concepts which permit to classify THF as a thymus hormone.     

Radioprotective effects of various cytokines in peripheral blood mononuclear cells and C3H mice

The purpose of this study was to investigate the radioprotective effect of HGFs (GM-CSF, IL-3 and SCF) in irradiated human peripheral blood mononuclear cells (PBMCs) in vitro, and the survival effect of lethally irradiated C3H mice in vivo. The irradiation of human PBMCs using a (137)Cs irradiator showed a dose-dependent inhibition of cell growth up to a dose of 5 Gy. This cell growth inhibition induced apoptosis, which was associated with the down-regulation of Bcl-2, up-regulation of Bax, depolarization of mitochondrial transmembrane potential (Delta psi m), and caspase-3 and -9 activation. Following gamma-irradiation at 2 Gy, IL-3 (10 ng/ml) alone or combined with SCF (50 ng/ml) reduced the apoptotic portion of human PBMCs by 15 and 20% of the cell population, respectively, showing no activation of caspase-3 compared to the control group. To examine the in vivo effect of gamma-irradiation and cytokines, we investigated the survival rate and recovery of peripheral blood cells in C3H mice. C3H mice subjected to total body irradiation (TBI) at a dose of 7 Gy (lethal dose 83% at 30 days) showed time-dependent decreases in RBC, WBC and platelet counts, with the nadir occurring at 12 to 15 days. However, treatment with recombinant murine (rm) SCF (2 microg/day s.c.), rmIL-3 (2 microg/day s.c.), or rmG-CSF (2.5 microg/day s.c.) 24 h before and after irradiation did not promote hematologic recovery or survival in the lethally irradiated C3H mice. These findings indicate that the combined treatment of IL-3 and SCF prevents the apoptosis induced in PBMCs by gamma-irradiation in vitro, but it does not afford any in vivo radioprotective effect in lethally irradiated C3H mice.     

Hand-sewn coloanal anastomosis for distal rectal cancer: Long-term clinical outcomes

As the oncologic safety of coloanal anastomosis (CAA) has been proved by many other authors, the incidence of CAA following ultralow anterior resection has increased. The purpose of this study is to evaluate the functional outcome and complications of patients who underwent ultralow anterior resection and CAA for distal rectal cancer. Fifty-seven patients underwent CAA following ultralow anterior resection between July 1997 and November 2003. Forty-four patients, who were followed up more than 6 months after diverting ileostomy closure, were evaluated for recurrence, complications, and functional outcomes. The mean follow-up period was 36.3 +/- 22.8 months (range, 8-83 months). The complications were multiple fistula (n = 3), fistula with anal stenosis (n=1), local recurrence with anal stenosis (n = 1), and anal stenosis (n = 7). Anal incontinence (Kirwan grade III) was noted in 14 patients, and bowel movements were observed more than six times per day in 16 patients. Overall recurrence occurred in six patients (13.6%). The 5-year survival rate was 85.3%, and the disease-free 5-year survival rate was 73.3%. Although CAA in patients with rectal cancer provides excellent long-term survival, a low risk of recurrence, and tolerable function, complications and poor functional outcomes of CAA do occur. Therefore, the choice of this method should be considered carefully.     

Determinants of response to a parent questionnaire about development and behaviour in 3 year olds: European multicentre study of congenital toxoplasmosis

Background  

We aimed to determine how response to a parent-completed postal questionnaire measuring development, behaviour, impairment, and parental concerns and anxiety, varies in different European centres.     

Expression profile of an operationally-defined neural stem cell clone

Neural stem cells (NSCs) are the most primordial and least committed cells of the nervous system, the cells that exist before regional specification develops. Because immunocytochemically-detectable markers that are sufficiently specific and sensitive to define an NSC have not yet been fully defined, we have taken the strong view that, to be termed a "stem cell" in the nervous system--in contrast to a "progenitor" or "precursor" (whose lineage commitment is further restricted)--a single neuroectodermally-derived cell must fulfill an operational definition that is essentially similar to that used in hematopoiesis. In other words, it must possess the following functional properties: (1) "Multipotency", i.e., the ability to yield mature cells in all three fundamental neural lineages throughout the nervous system--neurons (of all subtypes), astrocytes (of all types), oligodendrocytes--in multiple regional and developmental contexts and in a region and developmental stage-appropriate manner. (2) The ability to populate a developing region and/or repopulate an ablated or degenerated region of the nervous system with appropriate cell types. (3) The ability to be serially transplanted. (4) "Self-renewal", i.e., the ability to produce daughter cells (including new NSCs) with identical properties and potential. Having identified a murine neural cell clone that fulfills this strict operational definition--in contrast to other studies that used less rigorous or non-operational criteria for defining an NSC (e.g., the "neurosphere" assay)--we then examined, by comparing gene expression profiles, the relationship such a cell might have to (a) a multipotent somatic stem cell from another organ system (the hematopoietic stem cell [HSC]); (b) a pluripotent stem cell derived from the inner cell mass and hence without organ assignment (an embryonic stem cell); (c) neural cells isolated and maintained primarily as neurospheres but without having been subjected to the above mentioned operational screen ("CNS-derived neurospheres"). ESCs, HSCs, and operationally-defined NSCs--all of which have been identified not only by markers but by functional assays in their respective systems and whose state of differentiation could be synchronized--shared a large number of genes. Although, as expected, the most stem-like genes were expressed by ESCs, NSCs and HSCs shared a number of genes. CNS-derived neurospheres, on the other hand, expressed fewer "stem-like" genes held in common by the other operationally-defined stem cell populations. Rather they displayed a profile more consistent with differentiated neural cells. (Genes of neural identity were shared with the NSC clone.) Interestingly, when the operationally-defined NSC clone was cultured as a neurosphere (rather than in monolayer), its expression pattern shifted from a "stem-like" pattern towards a more "differentiated" one, suggesting that the neurosphere, without functional validation, may be a poor model for predicting stem cell attributes because it consists of heterogeneous populations of cells, only a small proportion of which are truly "stem-like". Furthermore, when operational definitions are employed, a common set of stem-like genes does emerge across both embryonic and somatic stem cells of various organ systems, including the nervous system.