Clofarabine and cytarabine combination as induction therapy for acute myeloid leukemia (AML) in patients 50 years of age or older

Outcome of patients with acute myeloid leukemia (AML) who are older than 60 years of age remains unsatisfactory, with low remission rates and poor overall survival. We have previously established the activity of clofarabine plus cytarabine in AML relapse. We have now conducted a phase 2 study of clofarabine plus cytarabine in patients aged 50 years or older with previously untreated AML. Clofarabine was given at 40 mg/m2 as a 1-hour intravenous infusion for 5 days (days 2 to 6) followed 4 hours later by cytarabine at 1 g/m2/d as a 2-hour intravenous infusion for 5 days (days 1 to 5). Of 60 patients, 29 (48%) had secondary AML, 30 (50%) had abnormal karyotypes (monosomy 5 and/or 7 in 15 [25%]), and 11 (21%) showed FLT3 abnormalities. The overall response (OR) rate was 60% (52% CR, 8% CRp). Four patients (7%) died during induction. Adverse events were mainly grade 2 or lower and included diarrhea, nausea, vomiting, mucositis, skin reactions, liver test abnormalities, and infusion-related facial flushing and headaches. Myelosuppression was common. Clofarabine plus cytarabine has activity in adult AML, achieving a good CR rate. However, survival does not appear to be improved compared with other regimens. Modifications of this combination in AML therapy of older patients warrant further evaluation.     

Motor cortex stimulation in rats with chronic constriction injury

Motor cortex stimulation (MCS) has gained a significant role in treatment of neuropathic pain. In order to evaluate effect of MCS in experimental animals we applied MCS to rats with neuropathic pain, which was evoked by chronic constriction injury (CCI) to the left sciatic nerve. Pain thresholds of both hind limbs were measured before, immediately after MCS, 1 h after MCS and 1 day after MCS. Effect of the stimulation was studied with respect to laterality (contralateral and ipsilateral MCS) and duration (short-term 10-min and long-term 1-h stimulation). It was found out that in control rats MCS did not affect thermal nociceptive thresholds. However, in CCI animals following results were obtained: difference score (difference in paw withdrawal latency between ligated and non-ligated hind limb) significantly decreased after both short- and long-term contralateral MCS; the difference score after the long-term ipsilateral MCS (related to the ligated hind limb) was not significantly different from that of intact animals; the effects of the contralateral short-term and the ipsilateral long-term stimulation faded within 1 h after the end of MCS, while the effect of the contralateral long-term MCS remained 1 h after the end of the MCS and faded within 24 h. It is concluded that MCS in experimental animals exerts similar effects as in human suffering from neuropathic pain and that the effect might be evoked from both cerebral cortices.     

Origin of the 31P MR signal at 5.3 ppm in patients with critical limb ischemia

An unknown intense signal (P_un) with a mean chemical shift of 5.3 ppm was observed in ³¹P MR spectra from the calf muscles of patients with the diabetic foot syndrome. The aim of the study was to identify the origin of this signal and its potential as a biomarker of muscle injury. Calf muscles of 68 diabetic patients (66.3 ± 8.6 years; body mass index = 28.2 ± 4.3 kg/m²) and 12 age‐matched healthy controls were examined by (dynamic) ³¹P MRS (3 T system, ³¹P/¹H coil). Phantoms (glucose‐1‐phosphate, P_i and PCr) were measured at pH values of 7.05 and 7.51. At rest, P_un signals with intensities higher than 50% of the P_i intensity were observed in 10 of the 68 examined diabetic subjects. We tested two hypothetical origins of the P_un signal: (1) phosphorus from phosphoesters and (2) phosphorus from extra‐ and intracellular alkaline phosphate pools. 2,3‐diphosphoglycerate and glucose‐1‐phosphate are the only phosphoesters with signals in the chemical shift region close to 5.3 ppm. Both compounds can be excluded: 2,3‐diphosphoglycerate due to the missing second signal component at 6.31 ppm; glucose‐1‐phosphate because its chemical shifts are about 0.2 ppm downfield from the P_i signal (4.9 ppm). If the P_un signal is from phosphate, it represents a pH value of 7.54 ± 0.05. Therefore, it could correspond to signals of P_i in mitochondria. However, patients with critical limb ischemia have rather few mitochondria and so the P_un signal probably originates from interstitia. Our data suggest that the increased P_un signal observed in patients with the diabetic foot syndrome is a biomarker of severe muscular damage.     

Role of oxidative stress in animal model of visceral pain

Reactive oxygen species play an important role both in physiological and pathophysiological reactions. The aim of this study was to determine the role of free radicals and antioxidants in the development of visceral pain. Visceral pain was produced by colorectal distension (CRD) in adult rats. CRD was caused by insertion of a lubricated latex balloon into the descending colon and rectum followed by inflation to 80 mm Hg for 10 min. During CRD, visceral pain was rated on 0–3.5 point scale. Oxidative stress was determined indirectly by measurement of free radical scavenging enzymes (glutathione peroxidase (GPx) and superoxide dismutase (SOD)) in the blood, liver and brain. Following CRD we observed (1) all rats expressed signs of visceral pain (overall rating was 1.83), (2) SOD and GPx levels were increased in the liver and blood, and decreased in the brain samples and (3) administration of the antioxidant Trolox, a water-soluble derivate of vitamin E, prior to CRD, prevented SOD and GPx changes in the liver, blood and brain, but did not affect pain scores. It was concluded, that CRD as a model of visceral pain, increases oxidative stress in animals, which could be prevented by prior administration of antioxidants; however, antioxidants did not attenuate signs of visceral pain caused by CRD.     

Dietary intake of energy and nutrients in relation to resting energy expenditure and anthropometric parameters of Czech pregnant women

Purpose

The aim of this study was to evaluate the dietary intake of energy and nutrients (DIEN) of Czech pregnant women and to assess relationships with body size variables during pregnancy.

Methods

One hundred and fifty-two randomly recruited healthy pregnant Czech women, who were normoglycemic, euthyroid, nonsmokers, not anemic, and not users of chronic medications or abusers of alcohol or drugs from countryside and city with different education, were recruited for the study. Anthropometric parameters were measured and resting energy expenditure obtained by indirect calorimetry after 12 h of fasting during four phases of pregnancy. DIEN was evaluated from self-reported dietary intake records over 7 days.

Results

Positive correlations were demonstrated between measured resting energy expenditure and intake of energy, substrates and some minerals and vitamins, and negative correlations between DIEN and anthropometric parameters. Lower dietary intake of energy and differences between dietary intake of nutrients and recommended daily allowances during pregnancy of Czech women were documented.

Conclusions

The difference between pregnancy body weight and ideal body weight was shown to be a determinant of DIEN. From recent knowledge on prevention of various pathological states, the supplementation or modification of nutritional intake of food with folate, iron, vitamin D, zinc, iodine and fiber for Czech pregnant women is recommended.     

Diffusion tensor imaging in Alzheimer disease and mild cognitive impairment

A wide range of imaging studies provides growing support for the potential role of diffusion tensor imaging (DTI) in evaluating microstructural white matter integrity in Alzheimer disease (AD) and mild cognitive impairment (MCI). Our review aims to present DTI principles, post-processing and analysis frameworks and to report the results of particular studies.The distribution of AD-related white matter abnormalities is widely discussed in the light of deteriorated connectivity within certain tracts due to secondary white matter degeneration; primary alterations are also assumed to contribute to the pattern. The question whether it is more effective to assess the whole-brain diffusion or to directly concentrate on specific regions remains an interesting issue. Assessing white matter microstructure alterations, as evaluated by group-level differences of tensor-derived parameters, may be a promising neuroimaging tool for differential diagnosis between AD, MCI and other cognitive disorders, as well as being particularly helpful in the interpretation of underlying pathological processes.     

The c-abl, bcr and C lambda genes are amplified in a cell line but not in the uncultured cells from a patient with chronic myelogenous leukemia

Structural alterations of the oncogenes in human tumors are reported to result from a variety of mechanisms: point mutations, chromosomal translocations and gene amplifications. In over 90% of the cases of chronic myelogenous leukemia (CML), the c-abl oncogene is translocated from chromosome 9 to chromosome 22, and forms in part the Philadelphia (Ph¹) chromosome.

We have molecularly analysed a double Ph¹-positive (Ph¹⁺) cell line, KBM-5 that was established from a patient with CML in the blast-transformed phase (CML-BP). We report that the c-abl, bcr, and Cλ genes are amplified approximately eight-fold in the cell line but not in the fresh uncultured cells from which KBM-5 was derived.