Elevated glucose concentrations during an oral glucose tolerance test are associated with the presence of metabolic syndrome in childhood obesity

Aims To investigate whether changes in glucose concentrations during an OGTT in obese children reflect the presence of peripheral insulin resistance and/or cardiovascular risk factors more closely than single measurements of fasting plasma glucose (FPG). Methods One hundred and twenty‐two obese children attending our Paediatric Obesity Service underwent formal OGTTs, following the measurement of blood pressure and fasting levels of insulin, glucose and lipid profiles in the majority. Fasting insulin was used as a surrogate measure of insulin sensitivity. Three different child‐specific definitions for metabolic syndrome were used to identify clustering of cardiovascular risk factors in 65 of these children. Results In the whole group, 10.7% had IGT but changes in glucose during the OGTT were not influenced by age, sex, pubertal status or raw (or age‐ and sex‐adjusted) body mass index (BMI). During the OGTT, FPG, glucose at 60 min and area under the glucose curve correlated highly with fasting insulin. Children with metabolic syndrome (defined using any of three definitions) had comparable FPG levels to those without metabolic syndrome, but they demonstrated significantly elevated glucose levels at 60 min. On sub‐group analysis, obese children with normal carbohydrate metabolism were significantly more likely to have a 1 h glucose level ≥ 7.8 mmol/l if they had metabolic syndrome (P = 0.026). Conclusions These data suggest that an elevated 1 h post‐load glucose measurement is seen in obese children who have a coexistent clustering of cardiovascular risk factors.     

Mixed lymphocyte reactivity and cell-mediated lympholysis to trinitrophenyl-modified autologous lymphocytes in C57BL/10 congenic and B10.A recombinant mouse strains

Cell-mediated lympholysis (CML) to trinitrophenyl (TNP)-modified autologous splenic lymphocytes has been recently reported in the mouse (1). Both the sensitization and effector phases of this phenomenon were shown to be T-cell mediated. Effector cell specificity studies indicated that modification of the target cells is a necessary but insufficient requirement for cytolysis, and suggested that altered cell surface components controlled by genes mapping in the mouse major histocompatibility H-2 complex (MHC) are important in the specificity of the cytotoxic reaction (1). In allogeneic models the generation of cytotoxic effector cells has been shown to be preceded or accompanied by immunogen- induced proliferation of responding lymphocytes, i.e. a mixed lymphocyte reaction (MLR) (2-5), although the generation of effectors may not necessarily always be the consequence of extensive cell proliferation (5). If the induction of cytotoxic effector lymphocytes by modified syngeneic spleen cells is characteristic of sensitization with cellular alloantigens, one would expect to find that sensitization with TNP-modified autologous cells would also induce thymidine incorporation by the responding cells in the culture. The present report demonstrates that both stimulation of thymidine incorporation and generation of cytotoxic effector cells are part of the in vitro response to TNP-modified autologous lymphocytes. However, the MLR to TNP- modified autologous cells consistently appeared to be less pronounced when compared with an allogeneic MLR, whereas the cytotoxic activity of the effector cells generated by sensitization against TNP-modified autologous cells was frequently as high as that detected against H-2 alloantigens. These two components of reactivity to “modified self” are verified in several C57BL/10 congenic and B10.A recombinant mouse strains.     

Large-volume leukapheresis in pediatric patients: processing more blood diminishes the apparent magnitude of intra-apheresis recruitment

Background: Recruitment of progenitors during a large-volume collection, as defined by increasing relative and absolute numbers of progenitors (colony-forming units-granulocyte-macrophage [CFU-GM] of CD34+ cells), has been reported previously. Study Design and Methods: To ascertain whether intra-apheresis recruitment occurs in pediatric patients who have undergone mobilization with chemotherapy and granulocyte-colony-stimulating factor (G-CSF), each hour's portion of a 4-hour leukapheresis was collected into separate bags, and assessed by complete blood count, CFU-GM, and CD34+ cell assays. Seven pediatric patients (median age, 7; range, 2–19) were studied in connection with 2 to 4 collections each, for a total of 21 collections (with hourly samples). The collections lasted for 4 hours, at an inlet rate of 1 to 3 mL per kg per minute, for daily processing totals of 5 to 12 blood volumes. (One blood volume [mL] is estimated by the patient's weight in kg × 70 mL/kg.) Smaller (younger) patients had inlet rates exceeding 2 mL per kg per minute, and larger (older) patients had rates of 1 to 1.5 mL per kg per minute. CFU-GM and CD34+ cell counts obtained each hour of the collection and divided by the first hour's value were compared by nonparametric repeated-measures ANOVA. Results: Second-, third- and fourth-hour CD34+ progenitor cell counts were arithmetically higher than first-hour counts, but the trend did not reach significance (p = 0.1561). Second-hour counts were higher than first-hour counts in the overall analysis (mean ± standard error [SE], 1.00 and 1.39 ± 0.1, respectively; p = 0.0525) and in children older than 5 years (1.00 vs. 1.70 ± 0.30, respectively; p = 0.0259), but not in children younger than 5 years (p = 0.8125). CFU-GM counts did not differ among the 4 hours of collection (p = 0.1717) or between the first and second hour (p = 0.9587). Conclusion: In larger (older) patients, from whom fewer blood volumes were collected, there is a trend toward intra-apheresis recruitment, although less than reported previously. In the smaller (younger) patients, from whom more blood volumes were collected, no trend was observed. Lack of (or submaximal) prior mobilization in previously reported studies may have facilitated intracollection recruitment. Alternatively, the larger number of blood volumes collected from the smaller (younger) patients may have masked intra-apheresis recruitment. The study documents the feasibility of large-volume, 4-hour leukapheresis in pediatric patients.     

The influence of bright light during the daytime upon circadian rhythm of core temperature and its implications for nocturnal sleep

Abstract The purpose of the present study was to investigate how bright light during the daytime could influence circadian rhythms of core temperature and nocturnal sleep. Seven females (age 20 ± 2 years) served as participants. The participants lived in the experimental unit for 4 days and were exposed to either 6000 lx (bright) or 200 lx (dim) light during the daytime. Rectal temperature (T_re) was measured during the experimental period. Subjective alertness was measured by the Kansei-gakuin Sleeping Scale five times a day. The minimum T_re was significantly lower after bright exposure ( P < 0.05). The T_re fell rapidly after bright exposure before they retired ( P < 0.05) and increased more rapidly during bright light after they woke up ( P < 0.05). The morning wakefulness under bright exposure was more active than under dim exposure ( P < 0.05). The melatonin secretion at wake up during bright exposure was significantly lower than during dim exposure ( P < 0.05). Exposure to bright light during daytime lowered the nocturnal level of T_re, its evening fall was faster and the morning rise quicker. This suggests that indoor light during daytime should be bright enough to promote healthy sleep at night.     

Strain and sex differences in amphetamine-induced rotation.

Studies of rotational behavior in female rats have investigated Fischer, Sprague-Dawley, Madison, WI, and Holtzman strains. The present study of amphetamine-induced rotational preference looked at the most widely used of the pigmented strains, Long-Evans hooded rats, examining rotation in females and comparing rotational magnitude and direction to males of the same strain. We corroborate in Long-Evans animals the greater rotation of females, but our findings oppose the right-sided female and left-sided male rotational preferences reported in earlier studies. Only female rats in this experiment had a significant directional bias, and it was to the left. This result strongly points to the importance of strain in the lateralization expressed by rotation.     

High-dose therapy and peripheral blood progenitor cell transplantation: effects of recombinant human granulocyte-macrophage colony-stimulating factor on the autograft

Between June 1989 and June 1992, 144 patients participated in sequential clinical trials using peripheral blood progenitor cells (PBC) as their sole source of hematopoietic rescue following high-dose chemotherapy. All patients had received prior extensive combination chemotherapy and had marrow defects that precluded autologous bone marrow transplantation (ABMT). PBC were collected according to a single apheresis protocol. The initial 86 patients (group 1) had PBC collected without mobilization. Beginning in April 1991, PBC were mobilized solely with recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF). Thirty-four patients (group 2) received rHuGM-CSF at a dose of 125 micrograms/m2/d by continuous intravenous infusion, and 24 patients (group 3) received rHuGM-CSF at a dose of 250 micrograms/m2/d by continuous intravenous infusion. Patients underwent at least six aphereses and had a minimum of 6.5 x 10(8) mononuclear cells (MNC)/kg collected. Cytokines were not routinely administered immediately after transplantation. A median of nine aphereses were required to collect PBC in group 1 and seven aphereses for groups 2 and 3 (P = .03). The time required to recover 0.5 x 10(9)/L granulocytes after transplant was significantly shorter (P = .0004) for the mobilized groups; the median time to recovery was 26 days for group 1, 23 days for group 2, and 18 days for group 3. Transplantation of PBC mobilized with rHuGM-CSF resulted in a shorter time to platelet (P = .04) and red blood cell (P = .01) transfusion independence. Mobilization with rHuGM-CSF alone resulted in efficient collection of PBC, that provided rapid and sustained restoration of hematopoietic function following high-dose chemotherapy. Mobilization of PBC with rHuGM-CSF alone is an effective method for patients who have received prior chemotherapy and have bone marrow abnormalities.     

Cytogenetic studies in patients with secondary leukemia/dysmyelopoietic syndrome after different treatment modalities

Cytogenetic studies of 68 patients who developed secondary leukemia (SL)/dysmyelopoietic syndrome (DMS) after extensive chemotherapy and/or radiation therapy as well as patients who developed SL/DMS without such treatment showed that those patients who received radiation alone or with chemotherapy had more extensive numerical and structural abnormalities than those who received only chemotherapy. In terms of the specific chromosomal abnormalities, there are no differences between the various treatment groups. Hypodiploidy is the most common form of aneuploidy in these patients, with the most common numerical abnormality being the loss of chromosome 7. The most common structural abnormalities involved chromosomes 3 and 5. When compared with patients with de novo leukemia and DMS, the chromosomal abnormalities in these patients are more complex and extensive. Serial studies revealed that cytogenetic abnormalities do not precede the development of hematologic changes by significant time periods.