The effect of thrombopoietin on the proliferation and differentiation of murine hematopoietic stem cells

In this study, we explored whether thrombopoietin (Tpo) has a direct in vitro effect on the proliferation and differentiation of long-term repopulating hematopoietic stem cells (LTR-HSC). We previously reported a cell separation method that uses the fluorescence-activated cell sorter selection of low Hoescht 33342/low Rhodamine 123 (low Ho/low Rh) fluorescence cell fractions that are highly enriched for LTR-HSC and can reconstitute lethally irradiated recipients with fewer than 20 cells. Low Ho/low Rh cells clone with high proliferative potential in vitro in the presence of stem cell factor (SCF) + interleukin-3 (IL-3) + IL-6 (90% to 100% HPP-CFC). Tpo alone did not induce proliferation of these low Ho/low Rh cells. However, in combination with SCF or IL-3, Tpo had several synergistic effects on cell proliferation. When Tpo was added to single growth factors (either SCF or IL-3 or the combination of both), the time required for the first cell division of low Ho/low Rh cells was significantly shortened and their cloning efficiency increased substantially. Moreover, the subsequent clonal expansion at the early time points of culture was significantly augmented by Tpo. Low Ho/low Rh cells, when assayed in agar directly after sorting, did not form megakaryocyte colonies in any growth condition tested. Several days of culture in the presence of multiple cytokines were required to obtain colony-forming units-megakaryocyte (CFU-Mk). In contrast, more differentiated, low Ho/high Rh cells, previously shown to contain short- term repopulating hematopoietic stem cells (STR-HSC), were able to form megakaryocyte colonies in agar when cultured in Tpo alone directly after sorting. These data establish that Tpo acts directly on primitive hematopoietic stem cells selected using the Ho/Rh method, but this effect is dependent on the presence of pluripotent cytokines. These cells subsequently differentiate into CFU-Mk, which are capable of responding to Tpo alone. Together with the results of previous reports of its effects on erythroid progenitors, these results suggest that the effects of Tpo on hematopoiesis are greater than initially anticipated.     

Hypertension in dialysis and kidney transplant patients

For the first time, the Canadian Hypertension Education Program has studied the evidence supporting blood pressure control in people requiring renal replacement therapy for end-stage kidney disease, including those on dialysis and with renal transplants. According to the Canadian Organ Replacement Registry’s 2008 annual report, there were an estimated 33,832 people with end-stage renal disease in Canada at the end of 2006, an increase of 69.7% since 1997. Of these, 20,465 were on dialysis and 13,367 were living with a functioning kidney transplant. Thus, it is becoming more likely that primary care practitioners will be helping to care for these complex patients. With the lack of large controlled clinical trials, the consensus recommendation based on interpretation of the existing literature is that blood pressure should be lowered to below 140/90 mmHg in hypertensive patients on renal replacement therapy and to below 130/80 mmHg for renal transplant patients with diabetes or chronic kidney disease.     

The coeliac iceberg in Italy. A multicentre antigliadin antibodies screening for coeliac disease in school-age subjects

Background : Recent studies suggest that coeliac disease (CD) is one of the commonest, life-long disorders in Italy. The aims of this multicentre work were: (a) to establish the prevalence of CD on a nationwide basis; and (b) to characterize the CD clinical spectrum in Italy. Patients and methods : Fifteen centres screened 17201 students aged 6–15 years (68.6% of the eligible population) by the combined determination of serum IgG- and IgA-antigliadin antibody (AGA) test; 1289 (7.5%) were IgG and/or IgA-AGA positive and were recalled for the second-level investigation; 111 of them met the criteria for the intestinal biopsy: IgA-AGA positivity and/or AEA positivity or IgG-AGA positivity plus serum IgA deficiency. Results : Intestinal biopsy was performed on 98 of the 111 subjects. CD was diagnosed in 82 subjects (75 biopsy proven, 7 not biopsied but with associated AGA and AEA positivity). Most of the screening-detected coeliac patients showed low-grade intensity illness often associated with decreased psychophysical well-being. There were two AEA negative cases with associated CD and IgA deficiency. The prevalence of undiagnosed CD was 4.77 × 1000 (95% CI 3.79–5.91), 1 in 210 subjects. The overall prevalence of CD, including known CD cases, was 5.44 × 1000 (95% CI 4.57–6.44), 1 in 184 subjects. The ratio of known to undiagnosed CD cases was 1 in 7. Conclusions : These findings confirm that, in Italy, CD is one of the most common chronic disorders showing a wide and heterogeneous clinical spectrum. Most CD cases remain undiagnosed unless actively searched.     

Oligosaccharides in human milk during different phases of lactation

Twenty-one oligosaccharides of human milk were quantified by high-performance anion-exchange chromatography. Milk samples were collected from 18 mothers during the first 3 mo of lactation. The data show that the highest amount of all oligosaccharides is present at day 4 postpartum (20 g l⁻¹) and then decreases by about 20% at day 30 of lactation. The protective role played by these substances against different infectious agents, in different organs and systems of the breastfed baby, is emphasized.     

Adolescents with type 1 diabetes and risky behaviour

Aim: The aim of the student is to assess whether adolescents with type 1 diabetes mellitus (T1DM) in Italy differ from their healthy peers in regard to risky behaviour. Methods: Data were collected from 215 patients, aged 14 ± 2 years with a mean disease duration of 7 ± 5 years. The control group was comprised of 464 healthy adolescents recruited among high school students. Each patient completed an anonymous confidential questionnaire to determine the prevalence of sexual behaviour, alcohol and tobacco consumption, illicit drug use, and, among patients with diabetes and frequency of mismanagement related to diabetes care. Results: Compared with controls, subjects with diabetes showed a similar rate of sexual intercourse among males and lower rates among females (34.8% vs 35.5%, p NS and 29.4% vs 41.4%, p < 0.05, respectively). Males in the diabetes group reported a higher rate of tobacco use, whereas females showed similar or higher rates of use for every illicit drug studied. Among patients with diabetes, those who are engaged in risky behaviour showed a higher rate of treatment mismanagement (76% vs 34%, p < 0.01). Conclusion: Adolescents with T1DM are as likely as their healthy peers to engage in risky behaviour, indicating the potential benefit of anticipatory guidance concerning glycaemic control and increased risk of acute and chronic complications.     

Prevalence and characteristics of brittle diabetes in Britain

We investigated the prevalence and characteristics of 'brittle diabetes', defined as insulin-dependent diabetes mellitus associated with glycaemic instability of any type, leading to life disruption with recurrent and/or prolonged hospitalizations. A questionnaire was sent to all physicians and paediatricians running diabetic clinics in the UK, from lists held at the British Diabetic Association. A total of 414 brittle patients were reported (72% questionnaire return). Most were young (mean age +/- SD was 26 +/- 15 years), though there was a small peak at ages 60-70 years. There was an excess of females (66%) and overall clinic prevalence was 1.2 per 1000 diabetic patients and 2.9 per 1000 insulin-treated diabetic patients. On average, there was 1.0 brittle patient per diabetic clinic. The most common form of brittleness was recurrent ketoacidosis (59%), with 17% having predominant hypoglycaemia, and 24% mixed instability. Female excess was highest and mean age lowest in the recurrent ketoacidosis group, whilst the reverse was true for those with recurrent hypoglycaemia. Causes of brittleness were offered by 58% of consultants, and most (93%) considered various psychosocial problems as likely underlying factors. We conclude that brittle diabetes is a small but significant problem, currently affecting about 1 per 1000 diabetic patients. Most, but by no means all, are young females--often with recurrent ketoacidosis. Older age groups are more likely to have recurrent hypoglycaemic or mixed types of brittleness. Perceived causes of brittleness are usually psychosocial.      

The quest for well‐being: self‐identified needs of women in chronic pain

Scand J Caring Sci; 2011; 25; 81–91
The quest for well‐being: self‐identified needs of women in chronic pain Women suffer more chronic pain in most Western countries than men, with considerable consequences for the sufferers. The aim of this phenomenological research was to study self‐reported needs of women in chronic pain. The data consisted of ten in‐depth interviews, which lasted from 60 to 120 minutes each, with five women in chronic pain, aged 36–53. Twelve needs were identified in the study, which were categorized into three clusters of needs or major quests: The quest to learn to live with the pain, which involves the need for diagnosis; the need to find effective treatment and keep the pain tolerable; the need for helpful advice and information and the need to take care of self and for a different pace and a new life pattern. The quest for support, caring and connection which involves the need for someone close who cares; the need to be connected to others and have someone to care for; the need for practical support e.g. financial support and household assistance and the need for professional support and caring. Finally, the quest for normalcy which involves the need to avoid the sick role and maintain a sense of dignity; the need to focus on personal strengths and prevent discouragement and depression; the need to be involved in decision‐making regarding own care and treatment and the need to participate in family and social activities to fight isolation and loneliness. The overriding theme in all these quests is the quest for well‐being; physically, mentally, emotionally and socially. Conflicting needs created five major dilemmas in the women’s lives. Women in chronic pain may be seen in any clinical setting and health professionals need to be able to recognize their needs in order to be able to give effective care, to cooperate with them and empower them.     

Maternal diet in early and late pregnancy in relation to weight gain

OBJECTIVE: To identify dietary factors related to the risk of gaining weight outside recommendations for pregnancy weight gain and birth outcome.Design:An observational study with free-living conditions.Subjects:Four hundred and ninety five healthy pregnant Icelandic women. METHODS: The dietary intake of the women was estimated with a semiquantitative food frequency questionnaire covering food intake together with lifestyle factors for the previous 3 months. Questionnaires were filled out at between 11 and 15 weeks and between 34 and 37 weeks gestation. Comparison of birth outcome between the three weight gain groups was made with ANOVA and Bonferroni post hoc tests. Dietary factors related to at least optimal and excessive weight gain during pregnancy were represented with logistic regression controlling for potential confounding. RESULTS: Of the women, 26% gained suboptimal and 34% excessive weight during pregnancy. Women in late pregnancy with at least optimal, compared with women with suboptimal, weight gain were eating more (OR = 3.32, confidence interval (CI)=1.81-6.09, P < 0.001) and drinking more milk (OR = 3.10, CI = 1.57-6.13, P = 0.001). The same dietary factors were related to excessive, compared with optimal, weight gain. Furthermore, eating more sweets early in pregnancy increased the risk of gaining excessive weight (OR=2.52, CI=1.10-5.77, P=0.029). Women with a body mass index of 25.0-29.9 kg/m(2) before pregnancy were most likely to gain excessive weight (OR = 7.37, CI 4.13-13.14, P < 0.001). Women gaining suboptimal weight gave birth to lighter children (P < 0.001) and had shorter gestation (P = 0.008) than women gaining optimal or excessive weight. CONCLUSION: Women who are overweight before pregnancy should get special attention regarding lifestyle modifications affecting consequent weight gain during pregnancy. They are most likely to gain excessive weight and therefore most likely to suffer pregnancy and delivery complications and struggle with increasing overweight and obesity after giving birth.     

Evaluating a family-centred intervention for infant sleep problems

AIM: This paper reports a study to describe changes in parents' distress after a family-centred intervention for sleep problems of infants. BACKGROUND: Infant sleep problems are common and are related to depressive symptoms in mothers, but their impact on fathers has rarely been studied. Because childhood sleep problems and parental distress are associated, their interdependence should be recognized in research and in paediatric sleep practice. METHODS: All children hospitalized for sleep problems in a hospital in Iceland in 1997-1998 and their parents were studied using a pre- and post-test quasi-experimental design. The sample consisted of 33 infants (6-23 months of age), 33 mothers and 30 fathers. Parents' distress was assessed before and after treatment with regard to: (1) fatigue and resulting symptom distress; (2) parenting stress; (3) state-anxiety; and (4) depressive symptoms. Infants were treated for a variety of sleep problems by a paediatric nurse. The parents were simultaneously treated for distress by either the paediatric nurse or a specialist, depending on the nature of their problems. RESULTS: Mothers and fathers experienced a high degree of distress before the intervention, with no significant difference between them. Two months after the intervention both parents' distress had significantly improved. Parents' degree of distress was at a psychopathological level before the intervention but was reduced to population norms 2 months after the intervention. The paediatric nurse intervention was sufficient to reduce distress for 83% of parents. CONCLUSIONS: Health care professionals who care for infants with sleep problems should pay attention to the distressed responses of parents and support their recovery. An intervention such as that described here could be used by nurses for this purpose.     

Patterns of Insulin Dependence in an African Diabetic Clinic

SUMMARY Analysis of the age of onset of diabetes amongst insulin-treatedpatients in a large African diabetic clinic revealed a bimodaltype of distribution, 23 per cent having an age of onset before30 years and 77 per cent with onset at 30 years of age. All66 of the young insulin-treated group (21.7±4.8 years(mean±1 SD)), and a random selection of 50 older insulin-treatedpatients (49.7±10 years), were studied. The older groupwere better controlled (HbA₁ 8.4±1.7 per cent vs. 10.8±2.6per cent, p<0.001), on lower doses of insulin (49±23vs. 71±23 u/day, p<0.001) and had higher body massindex (26.0±5.6 vs. 21.8±3.5, p<0.001). SerumC-peptide (0.24±0.15 vs. 0.07±0.10 nmol/l, p<0.0001),and C-peptide/glucose ratio (2.57±2.65 vs. 0.56+0.98nmol/mmolx 10², p<0.001) were very significantly higher inolder patients. Patients with later onset disease thus had betterpreservation of pancreatic function, higher body mass indexand better glycaemic control on lower doses of insulin. Thesefeatures suggest that older insulin-treated patients could infact be ‘Type 2’ or non-insulin dependent patients,and the condition may be controllable with diet and/or oralhypoglycaemic agents, at least in some.