Childhood growth and hypertension in later life

Few studies have examined the effects of both prenatal and postnatal growth on hypertension. We report on hypertension in 2003 people aged 62 years who were randomly selected from the Helsinki birth cohort and examined in a clinic. Their heights and weights had been recorded serially up to age 11 years. A total of 644 had already been diagnosed with hypertension. Compared with normotensive people, they were obese and insulin resistant. At birth they were thin and short, and they gained weight slowly up to age 2 years; thereafter they grew rapidly so that at age 11 years their body size was around the average. The odds ratio associated with each kilogram of birthweight was 0.42 (95% CI: 0.32 to 0.56); with each 10 kg of current weight it was 1.85 (95% CI: 1.66 to 2.05). The blood pressures of another 802 people were classified as hypertensive under current definitions. They were overweight and had an atherogenic lipid profile. At birth they were short, and after birth they grew slowly so that at age 11 years they were short and thin. The odds ratio associated with each kilogram of weight at age 2 years was 0.75 (95% CI: 0.68 to 0.84); with each 10 kg of current weight it was 1.42 (95% CI: 1.28 to 1.57). We conclude that 2 different paths of childhood growth precede the development of hypertension. We suggest that they lead to hypertension through different biological mechanisms and may respond differently to medication.     

A Randomized, Clinical Trial Comparing Butylcyanoacrylate with Octylcyanoacrylate in the Management of Selected Pediatric Facial Lacerations

OBJECTIVE: To compare two tissue adhesives, butylcyanoacrylate and octylcyanoacrylate, in the treatment of small (<4 cm) superficial linear traumatic facial lacerations in children. METHODS: This was a randomized, clinical trial with parallel design. 94 children <18 years of age seen in the ED of a tertiary care pediatric hospital with a facial laceration suitable for tissue adhesive closure underwent laceration closure using either butylcyanoacrylate or octylcyanoacrylate. The primary outcome was the cosmetic result at three months rated from photographs by a plastic surgeon on a visual analog scale (VAS). Secondary outcomes included the time to perform the procedure, the perceived difficulty of the procedure, the pain perceived by the patient, and a wound evaluation score at ten to 14 days and three months. RESULTS: Ninety-four patients were randomized with 47 in each group. The two groups were similar for baseline demographic and clinical characteristics. There was no difference in the three-month cosmesis VAS (median, 70.0 mm for n-butyl-2-cyanoacrylate vs 67.5 mm for octylcyanocrylate, p = 0.84). There was no difference between the groups for time to complete the procedure (p = 0.88), parent/patient-perceived pain of the procedure (p = 0.37), or physician-perceived difficulty of the procedure (p = 0.33). Similarly, there was no difference between the groups for the percentage of early (p = 0.58) or late (p = 0.71) optimal wound evaluation scores. CONCLUSIONS: In the closure of small linear pediatric facial lacerations, octylcyanoacrylate is similar to butylcyanoacrylate in ease of use and early and late cosmetic outcomes. The superior physical properties of octylcyanoacrylate appear to add little benefit to the management of these selected lacerations. Physician preference and differing costs may dictate use for these small selected lacerations.     

Support for Barker hypothesis upheld in rat model of maternal undernutrition during the preimplantation period: application of integrated 'random effects' statistical model

In response to a recent paper published in Reproductive BioMedicine Online by Walters and Edwards (2003), this study reports the application of a random effects regression analysis for evaluation of integrated data involving maternal and embryo/offspring components. Using this method, it is possible to confirm the conclusions of an earlier study that rat maternal undernutrition during the preimplantation period results in blastocyst cell number reduction and post-natal outcomes, including altered growth rates and elevated blood pressure.     

Testing the fetal origins hypothesis in twins: the Birmingham twin study

Aims/hypothesis. To test whether the link between birthsize and raised blood pressure or glucose tolerance is due to genetic or intrauterine factors, we studied whether differences in birthweight between pairs of monozygous and dizygous twins are associated with adult differences in blood pressure and glucose tolerance.¶Methods. A sample of 58 monozygous and 140 dizygous twins were identified from a register of births in Birmingham, United Kingdom, between 1950 and 1954. The twins had their blood pressure measured and underwent an oral glucose tolerance test.¶Results. There were no statistically significant associations between birthweight, length or ponderal index, and either blood pressure or glucose tolerance in the twins. Although there were substantial within-pair differences in birthweight between monozygous and dizygous twin pairs, these differences did not correlate with the adult outcomes. Monozygous correlations, however, for both blood pressure and glucose tolerance were statistically significantly higher than dizygous correlations and a quantitative genetic model suggested statistically significant heritability for these traits. In contrast correlations of birthsize were similar in monozygous and dizygous pairs suggesting only a small genetic component in determining fetal size.¶Conclusion/interpretation. Our results show that birthsize in twins does not predict adult blood pressure or glucose tolerance. We also suggest that shared genetic determinants for fetal growth and adult outcomes are not likely to be prevalent or powerful. [Diabetologia (2001) 44: 33–39]     

Placental glucose transport and utilisation is altered at term in insulin-treated, gestational-diabetic patients

Aims/hypothesis: We have previously shown that placentae from patients with gestational diabetes mellitus who did not receive insulin had lower glucose transport and utilisation than non-diabetic control subjects. To assess the placental glucose handling characteristics of women with gestational diabetes mellitus receiving insulin, we examined glucose transport and utilisation in placentae from three groups of women after term delivery: those with gestational diabetes mellitus and receiving insulin (n = 9, insulin group); those with gestational diabetes mellitus and not receiving insulin (n = 10, no insulin group); and those with normal, non-diabetic pregnancies (n = 9, control group). Methods: Dual perfusion of an isolated placental lobule was done using maternal glucose concentrations of 4, 8, 16 and 24 mmol/l. Glucose and l-lactate concentrations in the maternal and fetal effluents were measured. Direct glucose transfer from the maternal to the fetal effluent was measured using ¹⁴C-d-glucose. Mean rates in μmol ming^–1 (wet tissue) at maternal glucose concentration of 8 mmol/l are shown. Results: Glucose uptake from the maternal perfusate (insulin group 0.57, no insulin group 0.30) and net glucose transfer to the fetal effluent (insulin group 0.41, no insulin group 0.20) both increased in the placentae of women receiving insulin compared with the diabetic group not receiving insulin. Both groups of patients had lower placental glucose utilisation than the control group (insulin group 0.16, no insulin group 0.10, control group 0.25). Conclusion/interpretation: These results suggest that materno-fetal glucose transport increases in the placentae of women with gestational diabetes mellitus who receive insulin compared with those women who do not receive insulin. [Diabetologia (2001) 44: 1133–1139] Received: 19 February 2001 and in revised form: 17 April 2001     

Definition of an optimal cytotoxic T lymphocyte epitope in the latently expressed Kaposi's sarcoma-associated herpesvirus kaposin protein.

Cytotoxic T lymphocytes (CTL) recognize and kill virus-infected cells and contribute to immunologic control of viral replication. For many herpesviruses (e.g., Epstein-Barr and cytomegalovirus), virus-specific CTL responses can be readily detected in infected persons, but CTL responses against Kaposi's sarcoma-associated herpesvirus (KSHV) appear to be weak and remain poorly characterized. Using a human leukocyte antigen (HLA) binding motif-based epitope prediction algorithm, we identified 37 HLA-A*0201 binding peptides from 8 KSHV open-reading frames (ORFs). After in vitro stimulation of peripheral blood mononuclear cells from KSHV-infected persons, CTL responses against 1 peptide in the KSHV kaposin protein (ORF K12) were detected in 2 HLA-A*0201-positive subjects. The optimal CTL epitope was identified by HLA restriction analysis and peptide titration assays. These data describe a latent phase viral gene product targeted by CTL that may be relevant for KSHV immunopathogenesis.     

Melatonin inhibits apoptosis during early B-cell development in mouse bone marrow

The pineal secretory product, melatonin, exerts a variety of effects on the immune system. Administration of melatonin stimulates cell-mediated immunity, particularly by inhibiting apoptosis among T lymphocytes in the thymus and inducing production of T-cell-derived cytokines. However, its possible effects on the humoral immune system are unclear. In the present study, we have examined whether melatonin may influence the in vivo development of B lymphocytes in mouse bone marrow, a process in which apoptosis is normally a prominent feature. Double immunofluorescence labeling and flow cytometry were used to quantitate phenotypically defined precursor B-cell and mature B-cell populations and their apoptotic rates in bone marrow of mice fed either melatonin-containing or control diet for 16 days from 9 wk of age. In short-term bone marrow cultures, the incidence of apoptosis among large pre-B cells, including cells expressing the lambda5 component of pre-B-cell receptor, was markedly reduced in melatonin-treated mice, associated with an increase in the absolute number of large pre-B cells in bone marrow. In contrast, apoptosis of earlier precursor B cells and mature B lymphocytes did not differ from control values. The results indicate that orally administered melatonin can substantially promote the survival of precursor B cells in mouse bone marrow. Melatonin treatment may thus boost the survival of newly formed B cells mediating humoral immunity.     

The fetal and childhood growth of persons who develop type 2 diabetes

BACKGROUND: Type 2 diabetes is associated with low birthweight followed by obesity in adulthood. Persons who develop the disease may therefore have a particular pattern of growth from birth through childhood. OBJECTIVE: To examine the relation of type 2 diabetes to size at birth and childhood growth. DESIGN: Cohort study. SETTING: Helsinki, Finland. PARTICIPANTS: Men (n = 3,639) and women (n = 3,447) who were bom at the Helsinki University Central Hospital between 1924 and 1933, who went to school in Helsinki, and who still lived in Finland in 1971. Detailed birth and school health records were available for all 7,086 participants. We identified 471 men and women who developed type 2 diabetes by using the national Social Insurance Institution's register of all persons in Finland who are receiving long-term therapy with medication. MEASUREMENTS: Incidence of diabetes ascertained from a national register. The main explanatory measurements were size at birth and childhood growth in terms of height, weight, and body mass index. RESULTS: The cumulative incidence of type 2 diabetes was 7.9% (n = 286) in men and 5.4% (n = 185) in women. The incidence increased with decreasing birthweight, birth length, ponderal index (birthweight/length(3)), and placental weight The odds ratio for type 2 diabetes was 1.38 (95% CI, 1.15 to 1.66; P < 0.001) for each 1-kg decrease in birthweight. The mean weights and heights of the children at 7 years of age who later developed type 2 diabetes were about average. Thereafter, their growth in weight and height was accelerated until 15 years of age. The odds ratio for development of type 2 diabetes was 1.39 (CI, 1.21 to 1.61; P < 0.001) for each standard deviation increase in weight between 7 and 15 years of age. The odds ratio became 1.83 (CI, 1.37 to 2.45; P< 0.001) in an analysis restricted to persons whose birthweights were below 3,000 g. Children of both sexes whose mothers had a high body mass index in pregnancy had more rapid growth during childhood and an increased incidence of type 2 diabetes. CONCLUSIONS: These findings are consistent with the hypothesis that type 2 diabetes is programmed in utero in association with low rates of fetal growth. The increased risk for type 2 diabetes associated with small size at birth is further increased by high growth rates after 7 years of age.