Oncogene expression in primary myelodysplasia: correlation with haematological, karyotypic, and clinical progression.

AIMS: To see if the relative expressions of proto-oncogenes that are increased in acute myeloid leukaemia are raised in patients with myelodysplastic syndromes (MDS), and to see if they increase with progression to leukaemia. To note if there is a correlation between morphology, karyotype, and these proto-oncogene expressions and if any one proto-oncogene can predict prognosis. METHOD: Bone marrow from 130 patients was analysed at six monthly intervals over two years for relative mRNA expression of seven oncogenes, karyotype, and morphology. The technique used slot blot hybridisation and densitometric analysis. The results were compared with 14 surgical controls and 30 people with vitamin deficiency anaemia. RESULTS: Six of seven oncogenes showed increased expression which progressed with time, but did not correlate with morphological or karyotypic changes. Expression of four of the seven oncogenes was increased in megaloblastic and iron deficiency anaemia. C-mos showed differences among the five morphological subgroups; it correlated with abnormal location (p = 0.025) and seemed to influence prognosis. CONCLUSION: Increased proto-oncogenes reflect the overall marrow perturbation in MDS. C-mos may reflect persistence of monocyte pathway which confirms marrow stability.     

Apolipoprotein (a) levels and phenotypes in NIDDM patients with microalbuminuria and albuminuria

This study was conducted to determine whether circulating levelsof lipoprotein (a), an independent risk factor of macrovasculardisease, are increased in non-insulin-dependent diabetes mellitus(NIDDM) patients with microalbuminuria who have an increasedrisk of cardiovascular mortality. Apolipoprotein (a) [apo(a)levels and phenotypes, and other circulating lipid levels weredetermined in 227 Chinese NIDDM patients with varying stagesof diabetic nephropathy. None was on lipid-lowering therapy.Apo(a) levels in normoalbuminuric (geometric mean 166 U/L; 95%confidence intervals 137, 200; n = 105) and microalbuminuricpatients (162; 132, 209; n = 77) were similar to values in controls(166; 143, 193, n = 168). Albuminuric patients, however, hadhigher apo(a) levels than both normoalbuminuric patients andcontrols (242; 184, 317; n = 45; p <0.05). The overall sizerange of the apo(a) phenotypes and the frequency of having atleast one small isoform, i.e. <700 kDa, were similar amongthe four groups of subjects. A positive correlation was foundbetween log apo(a) and log plasma creatinine levels (p<0.01).Compared to normoalbuminuric patients, both microalbuminuricand albuminuric patients were older (p<0.01) and had higherHbA1c (p<0.01), greater BMI (p<0.05) and longer diseaseduration (p< 0.05) compared to normoalbuminuric patients.Nevertheless, using multiple linear regression analysis, itwas found that the presence of nephropathy conferred an independentinfluence on increasing total cholesterol (p<0.001), triglyceride(p< 0.001) and apoB (p<0.01), and decreasing HDL cholesterol(p<0.05) levels even when only the normoalbuminuric and microalbuminuricgroups were analysed. The prevalence of macrovascular diseasewas significantly increased in microalbuminuric and albuminuricpatients (45.1 and 48.7% respectively vs 20.2% in normoalbuminuricpatients, p<0.01). It is concluded that circulating apo(a)levels were not increased in Chinese NIDDM patients with microalbuminuria.However, atherogenic changes in other lipid and lipoproteinlevels may contribute to an increased risk of macrovasculardisease in these patients.     

A relapse of paratyphoid fever after treatment with ciprofloxacin in a child with congenital biliary atresia

This report describes a relapse of Salmonella paratyphi B infection in a child with biliary atresia, following 2 weeks of treatment with ciprofloxacin. The recrudescence was complicated by the development of osteomyelitis and was treated with chloramphenicol, trimethoprim, ceftriaxone and ampicillin in succession.     

雌二醇对动情间期切除卵巢母羊黄体生成素分泌脉冲的抑制作用

动情间期母羊切除卵巢并皮下植入持续释放的E_2后,平均LH基础分泌水平和LH脉冲幅高比对照组显著减低,LH脉冲频率无明显改变。LH的平均基础分泌水平和脉?中幅高显著相关。表明植入E_2对垂体LH分泌的抑制作用主要是抑制LH对GnRH的反应,作用部位在垂体,不在下丘脑。LH基础分泌水平的下降,亦可能是E_2的抑制作用所致。     

The Asp84Glu variant of the melanocortin 1 receptor (MC1R) is associated with melanoma

Melanocyte stimulating hormone (MSH) plays an important role in determining the cutaneous response to ultraviolet radiation and may also influence melanoma progression. We have previously shown that variants of the melanocortin receptor present on melanocytes, MC1R, are associated with sun sensitivity and red hair in a UK population and therefore now consider the gene as a candidate for melanoma susceptibility. We have compared the frequency of known MC1R variants in the second and seventh transmembrane domains in 43 melanoma cases and 44 controls. MC1R variants were more common in cases than controls (chi 2 = 6.75, 1 d.f.; P = 0.0094) with a relative risk to carriers of variant alleles compared with normal homozygotes of 3.91 (95% c.l.: 1.48-10.35), and a population risk attributable to carriers of 34.6% (95% c.i. 10.7-52.1%). The Asp84Glu variant was only present in melanoma cases and appears to be of particular significance. The contribution of variant MC1R alleles was largely independent of skin type. Variants of the MC1R gene are likely to be causally associated with the development of melanoma.      

Bronchodilator Responses to Salbutamol Using Diskhaler Versus Metered-Dose Inhaler

In adults inhaling salbutamol via metered-dose inhalers (MDIs) 200 μ.g doses are recommended, but with diskhalers the manufacturer advocates 400 rather than 200 µg doses. To assess this advice, a partially double-blind, placebo-controlled salbutamol dose response, crossover study (also incorporating MDI doses) was conducted in 12 mild/moderate asthmatics. After active treatment, mean peak expiratory flow rate (PEFR) increments yielded no clinically or statistically significant differences; compared to placebo, respective median differences in PEFR increments (95% CIs) were 10 (-10, 50), 20 (0, 50), and 15 (0, 30) following 400 and 200 µg via diskhalers and 200 u.g via MDIs. Diskhalers are a suitable alternative for patients with poor MDI technique, but the use of 400 rather than 200 µg salbutamol doses is not supported by evidence.     

Maintenance of growth in cystic fibrosis despite reduction in pancreatic enzyme supplementation

Twenty one children with cystic fibrosis were advised to decrease their pancreatic enzyme supplement (PES) dose to less than 10,000 units lipase/kg/day. Mean PES dosage was significantly decreased in 15 patients from 18,380 to 8647 units lipase/kg/day. There were no significant changes in energy or fat intake, but there were significant increases in weight SD score, height SD score, and weight/height ratio.     

Morphogenetic roles of acetylcholine

In the adult nervous system, neurotransmitters mediate cellular communication within neuronal circuits. In developing tissues and primitive organisms, neurotransmitters subserve growth regulatory and morphogenetic functions. Accumulated evidence suggests that acetylcholine, (ACh), released from growing axons, regulates growth, differentiation, and plasticity of developing central nervous system neurons. In addition to intrinsic cholinergic neurons, the cerebral cortex and hippocampus receive extensive innervation from cholinergic neurons in the basal forebrain, beginning prenatally and continuing throughout the period of active growth and synaptogenesis. Acute exposure to ethanol in early gestation (which prevents formation of basal forebrain cholinergic neurons) or neonatal lesioning of basal forebrain cholinergic neurons, significantly compromises cortical development and produces persistent impairment of cognitive functions. Neonatal visual deprivation alters developmental expression of muscarinic acetylcholine receptors (mAChR) in visual cortex, whereas local infusion of mAChR antagonists impairs plasticity of visual cortical neurons. These findings raise the possibility that exposure to environmental neurotoxins that affect cholinergic systems may seriously compromise brain development and have long-lasting morphologic, neurochemical, and functional consequences.