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.     

Effect of intravascular laser irradiation of blood on growth and metastasization of lymphosarcoma in rats

Research Institute of Oncology and Research Institute of Pharmacology, Tomsk Scientific Center, Academy of Medical Sciences of the USSR. (Presented by Academician of the Academy of Medical Sciences of the USSR N. V. Vasil'ev.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 106, No. 10, pp. 472–473, October, 1988.     

Diagnostic problems of autoimmune thyroiditis

The most informative diagnostic criteria of autoimmune thyroiditis were revealed. A kit of diagnostic tests were offered for each version of autoimmune thyroiditis. The lowest percentage of antibodies against thyroglobulin was demonstrated for the hyperthyroid hypertrophic version of autoimmune thyroiditis, while the highest for its atrophic pattern. Biopsy of the thyroid was found to be the most informative test for autoimmune thyroiditis, provided the result was positive. If the result of puncture biopsy is negative, it is desirable to apply a complex of tests depending on thyroid function and size.     

Status of the hypophysis-adrenal cortex system during treatment with glucocorticoids by the method of intermittent (every other day) administration

The authors discuss the advantages of the use of glucocorticoids in the treatment of autoimmune diseases, if the drugs are administered every other day. A total of 149 patients with autoimmune thyroiditis, endocrine ophthalmopathy, myasthenia and bronchial asthma were examined. Of these, 3 patients received glucocorticoids every other day, whereas the remainder took them every day. The former method consisted in the use of a single daily dose of glucocorticoids (20 to 80 mg) at 7 to 8 o'clock in the morning over 2 months to 5 years. The function of the pituitary-adrenal system was tested by the measurement of the blood content of ACTH, hydrocortisone and testosterone with the aid of a kit of standard tests. It was shown that glucocorticoids administered every other day did not produce any suppression of the pituitary-adrenal system in contrast to those who received prednisolone every day. The lack of the side effects in the form of exogenous hypercorticoidism can be explained by the anabolic action of steroid hormones produced by the reticular zone of the adrenal cortex. Examination of the blood serum content of testosterone in women who received glucocorticoids every other day has demonstrated that modulations in its secretion were similar to those in the content of ACTH and hydrocortisone. Thus, the stimulating hormonal therapy with glucocorticoids administered every other day appears more physiological as compared to the daily schedule.     

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.