Growth characteristics of circulating hematopoietic progenitor cells from patients with essential thrombocythemia

Peripheral blood mononuclear cells from five patients with essential thrombocythemia (ET) were cultured in vitro to evaluate restricted megakaryocytic (CFU-Meg), myeloid (CFU-GM), and erythroid (BFU-E) progenitor cell development. Varying concentrations of aplastic canine serum served as the source of megakaryocyte colony-stimulating activity, and cultured megakaryocyte ploidy distributions were determined by Feulgen staining and microfluorometry. Megakaryocyte colony growth was strikingly abnormal in all five patients evaluated. Four of the 5 had a marked expansion in the concentration of circulating CFU-Meg and 3 of 4 manifested abnormalities in cultured megakaryocyte colony size (2 unusually large and 1 small). Unstimulated megakaryocyte colony growth was substantially increased in three patients. However, the fraction of megakaryocyte progenitors in cell cycle was near or below normal in all instances. Endomitotic megakaryocyte development was disordered in each of the four ET patients in whom it was evaluable. In normal subjects, mean megakaryocyte ploidy values vary biphasically with aplastic canine serum concentration and peak at 13.2 N following 12 to 15 days of culture. In contrast, day 12 mean ploidy values in cultures from the ET patients remained low at all aplastic canine serum concentrations and reached a maximum averaging only 8.4 N. Three patients were evaluated serially at extended culture durations of up to 21 days. The cultured megakaryocyte ploidy was unchanged during this interval for two of the patients. For the third patient, ploidy increased steadily, reaching abnormally high ploidy values by day 21. Progenitor cell expansion was limited to the megakaryocyte line in three patients. However, two patients had substantial increases in CFU-GM, one of whom also had a marked increase in BFU-E. There was no significant unstimulated colony growth by either CFU-GM or BFU-E. These data indicate that ET is usually characterized by an expansion in the concentration of circulating CFU-Meg in vivo which manifest both disordered replication and endoreduplication in vitro.     

Ring opening polymerization of L-methyl 2-(2-methyl-1-aziridinyl)acetate and its racemic stereoisomer: 13C NMR study

Poly[L (and D , L )-N-(methoxycarbonylmethyl)iminopropylene] ( 5 ) were synthesized by cationic polymerization of methyl 2-(2-methyl-1-aziridinyl)acetate ( 4 ) in the presence of dimethyl sulfate as initiator. The stereoregularity of the polymer obtained from the L -aziridine 4 was determined by ¹³C NMR study of the L - and D ,L -polyesters 5 . It could be shown that the opening of the aziridine ring proceeds mainly at the unsubstituted methylene carbon atom, retaining the configuration of the asymmetric carbon to at least 85%.     

Diminished concentrations of insulin-like growth factor I in cystic fibrosis

Cystic fibrosis is frequently accompanied by a catabolic condition with low body mass index caused by a number of disease complications. Insulin-like growth factor-I (IGF-I) is an anabolic hormone and an important marker of nutritional status, liver function, and linear growth. Available data on IGF-I in cystic fibrosis are sparse and conflicting. From 1990-3, 235 of our 240 patients (114 males, 121 females, median age 16.2 years, ranged 0.1-44.0 years) had IGF-I measured once by radioimmunoassay. IGF-I was significantly reduced compared with a healthy Scandinavian control population: mean (-2 SD to +2 SD) IGF-I SD score was -0.97 (-3.7 to 1.7) in males and -0.67 (-3.2 to 1.9) in females. Height SD score was -0.95 (-3.3 to 1.4) in males and -0.81 (-3.2 to 1.6) in females. In patients who were still in the growth period a significant correlation of IGF-I SD score to height SD score (r = 0.28, p < 0.001) was found. The low IGF-I concentrations may reflect the catabolic state of many patients with cystic fibrosis and play a part in their abnormal growth pattern.     

Congenital toxoplasmosis presenting as massive neonatal ascites

A preterm infant with isolated transudative ascites caused by Toxoplasma gondii is described. In the absence of obvious congenital malformations, toxoplasmosis should be considered in the differential diagnosis of fetal and neonatal non-immune ascites.     

Recommended structure for reporting economic evaluation on pharmaceuticals in Belgium

Pharmacoeconomic evaluations become more important for the reimbursement of pharmaceuticals, and will be obligatory for new pharmaceutical drugs for which an added therapeutic value is claimed and a price premium is proposed by the manufacturer. Therefore, it is important to guide purchasers and providers of pharmaceutical care in their efforts related to the evaluation process. Standard Report Format can support the quality, transparency and exhaustiveness of the data submitted. A multidisciplinary task force developed a Standard Report Format for pharmacoeconomic evaluations in Belgium.     

Magnetic resonance imaging in tracheal compression by the innominate artery

Tracheal compression by the innominate artery is frequently suspected in infants with noisy breathing and no obvious aortic arch anomalies or pulmonary artery sling. However the diagnosis is difficult to confirm. The findings after using magnetic resonance imaging in two infants with tracheal compression syndrome are presented.     

Physiological anticoagulants and activated protein C resistance in childhood stroke

Immunological and functional protein S, protein C and antithrombin III levels and anticoagulant responses to activated protein C were measured in 24 patients with stroke in childhood. No hereditary deficiencies were found. The protein S levels in healthy controls of younger age did not differ from the adult levels. For optimal screening of protein S deficiency, measurements using functional as well as immunological assays are recommended. Appropriate criteria for the diagnosis of the deficiencies must be carefully applied if unnecessary anxiety and inappropriate treatment of children are to be avoided.     

Evaluation of attempted prevention of unexpected infant death in very high-risk infants by planned health care

Three hundred and ninety-six babies born in Sheffield between 1982 and 1990 identified as being at "very high risk" of unexpected infant death by means of a scoring system, received an intensive programme of health care including a case discussion between a paediatrician, the GP and the health visitor held in the family doctor's surgery, weekly visits from the health visitor and informal hospital admission. Significantly fewer sudden unexpected infant deaths occurred in this group than were expected by logistic regression anlysis or occurred in the best available control group with comparable scores ( p = 0.024). Problems in evaluation include identification of an adequate control population, ethical difficulties in introducing a controlled study when the programme is already perceived as effective, and the calculation of "expected death rates". The results of this study indicate that very energetic programmes of intervention may prevent some deaths in vulnerable infants.     

Magnetic resonance imaging in tracheal compression by the innominate artery.

Tracheal compression by the innominate artery is frequently suspected in infants with noisy breathing and no obvious aortic arch anomalies or pulmonary artery sling. However the diagnosis is difficult to confirm. The findings after using magnetic resonance imaging in two infants with tracheal compression syndrome are presented.     

Fatigue, sexual function and mood following treatment for haematological malignancy: the impact of mild Leydig cell dysfunction

Fatigue, sexual dysfunction, anxiety and depression are all more common in patients who have previously been treated with cytotoxic chemotherapy and radiotherapy (XRT) for haematological malignancies. Following therapy, a significant proportion of men have biochemical evidence of Leydig cell dysfunction, defined by a raised luteinizing hormone level in the presence of a low/normal testosterone level. We postulated that mild testosterone deficiency may account for some of the long-term side-effects of treatment, and we have therefore assessed fatigue, mood and sexual function by questionnaire in 36 patients with Leydig cell dysfunction (group 1), and also in a group of 30 patients (group 2) with normal hormone levels who underwent the same treatment for cancer. There was no significant difference in anxiety and depression scores between the two groups although anxiety scores were higher than those previously reported for normal men. Eighty-seven per cent of group 2 were sexually active compared with only 69% of group 1 (P= 0.1), and patients in group 1 engaged less in sexual activity than those in group 2 (mean of 1.8 times per week compared with 3.2 times per week; P = 0.02) Fatigue scores were significantly higher in both groups compared with normal men, but there were no significant differences in any of the fatigue subscales between the two groups. We conclude that mild Leydig cell insufficiency following treatment with cytotoxic chemotherapy +/- XRT is not associated with higher levels of fatigue and anxiety but may result in reduced sexual function. These results do not provide a convincing argument that androgen replacement therapy is mandatory to improve quality of life in the majority of these patients, although it may be beneficial in a minority. To establish criteria for selection of patients for a trial of androgen therapy a randomized placebo-controlled study will be necessary.