Biological characteristics of newly diagnosed poor prognosis acute myelogenous leukemia

A pilot study was conducted of the biological characteristics of the leukemia cells of newly diagnosed patients with poor prognosis acute myelogenous leukemia (AML). This study included measurements of the pretherapy proliferative rate of the leukemia cells in vivo, assessment of differentiation in vivo during remission induction therapy, and the level of expression of the fms, myc, and IL1β genes in pretherapy leukemia cells. Short cell cycle times were characteristic of the best prognostic category and were associated with a rapid reduction in marrow leukemia cells in cytosine arabinoside (araC)-sensitive patients. Expression of c-fms was associated with rapid reduction in marrow leukemia cells during araC therapy and with a successful treatment outcome. Expression of the IL1β gene was associated with short remissions. These studies suggest that when compared to newly diagnosed standard prognosis AML, the leukemia of poor prognosis patients is more likely to exhibit long cell cycle times, low levels of fms expression, and is less likely to be associated with myeloid differentiation during remission induction therapy. © 1993 Wiley-Liss, Inc.     

Mesangial expansion at 5 years predicts death and death‐censored graft loss after renal transplantation

Death with a functioning graft and death‐censored renal allograft failure remain major problems for which effective preventative protocols are lacking. The retrospective cohort study aimed to determine whether histologic changes on a 5‐year surveillance kidney biopsy predict adverse outcomes after transplantation in recipients who had: both Type 2 diabetes (T2DM) and obesity (BMI ≥ 30 kg/m²) at the time of transplantation (T2DM/Obesity, n = 75); neither (No T2DM/No obesity, n = 78); No T2DM/Obesity (n = 41), and T2DM/No obesity (n = 47). On 5‐year biopsies, moderate‐to‐severe mesangial expansion was more common in the T2DM/Obesity group (Banff mm score ≥2 = 49.3%; Tervaert classification MS ≥ 2b = 26.7%) compared to the other groups (p < .001 for both scores). Risk factors included older age, higher BMI, HbA1C, and triglycerides at 1‐year post‐transplant. Moderate‐to‐severe mesangial expansion correlated with death with function (HR 1.74 (1.01, 2.98), p = .045 Banff and 1.89 (1.01, 3.51) p = .045 Tervaert) and with death‐censored graft loss (HR 3.2 (1.2, 8.8), p = .02 Banff and HR 3.8 (1.3, 11.5), p = .01 Tervaert) over a mean of 11.6 years of recipient follow‐up post‐transplant. These data suggest that mesangial expansion in recipients with T2DM and obesity may reflect systemic vascular injury and might be a novel biomarker to predict adverse outcomes post renal transplant.     

Occupational risks for human reproduction: ELSPAC Study. European Longitudinal Study of Pregnancy and Childhood

Pregnant women living in Brno who were contacted for the first time at 18th week of their pregnancies during the period from February 1990 to January 1992 were involved into the ELSPAC group. Among others, the exposure to different occupational factors in the three periods was obtained by the self-reported questionnaire: 1. the last 9 months before pregnancy, 2. the first, and 3. second trimester periods. The women's health status during pregnancy, the history of delivery and the developmental and health status of newborns were described in details by obstetrics and pediatrics according to another internationally unified questionnaire. All data obtained from 3,897 pregnant women living in Brno were computered. Smoking women were significantly more often than non-smokers occupationally exposed to ergonomic stressors associated with the monotony work, and to chemical substances. In the whole group, the intrauterine growth retardation has been positively associated with shifting (OR 1.59, p < 0.05) and occupational exposure to permanent noise (OR 1.92, < 0.05). Newborns of such exposed women had in average lower parameters of head cimcumstances (p < 0.01). Non-physiologic, non-spontaneous deliveries have been more often observed among VDTs users (OR 1.20-1.28, p < 0.05). Women exposed to organic solvents during 2nd trimester of pregnancy delivered more often babies with some congenital malformations (OR 2.31, p < 0.05). On the other hand, the different occupational factors seemed to be protective for several markers of the women health status, as the prevalence of reproductive damages was significantly lower among exposed women than in the non-exposed group. After the standardization of the smoking habit, more significant associations have occurred in the group of smokers occupationally exposed to: shift work (low-birth-weight babies: OR 1.98, p < 0.05), chemicals (bleeding during pregnancy: OR 2.00, p < 0.05), sedentary work (placental abnormalities and congenital malformations: OR 1.59, p < 0.05). Non-smoking women using VDTs had more often babies with intrauterine growth retardation (OR 2.29, p < 0.05). Newborns with different malformations were more often born to non-smoking women occupationally exposed to chemicals (OR 2.33, p > 0.05).     

Some reasons for the lack of progress in the treatment of acute myelogenous leukemia: a review of three consecutive trials of the treatment of poor prognosis patients

The failure of three consecutive treatment protocols to significantly increase the complete remission rate for poor prognosis newly diagnosed patients with acute myelocytic leukemia led to a detailed investigation of the causes of treatment failure. In the majority of cases treatment failure was attributable to "clinical resistance" to therapy. Upon close examination two types of "clinical resistance" were discernible: the failure of chemotherapy to produce adequate cytotoxic effects ("classical" drug resistance), and treatment failure attributed to the rapid regrowth of leukemia cells subsequent to the substantial killing of leukemia cells by cytotoxic therapy ("biological" resistance). Each form of resistance accounted for one-half of the treatment failures.     

Vasospastic Angina with J‐Wave Pattern and Polymorphic Ventricular Tachycardia Effectively Treated with Quinidine

Background: Myocardial ischemia during coronary spasm may generate malignant ventricular arrhythmias. The J‐wave pattern was suggested to be a marker of a disorder associated with life‐threatening arrhythmias. Results: We report the case of a patient with vasospastic angina and J‐wave pattern in inferior and lateral leads associated with polymorphic ventricular tachycardia which was effectively treated only with quinidine—vasodilating drugs were not able to prevent the arrhythmia although they were effective in preventing ischemic events. Conclusion: The J‐wave pattern in inferolateral leads may be a sign of electrical vulnerability to lethal ventricular arrhythmia in patients suffering from vasospastic angina—quinidine can effectively prevent such arrhythmias in these patients.     

U Wave Variability in the Surface ECG

A 72‐year‐old man with heart failure, left ventricular dysfunction (ejection fraction 20%), prior ischemic stroke, COPD, and exacerbation of chronic renal failure was admitted in our unit. Serum potassium was 6.1 mmol/L, calcium concentration was at the lower normal range 2.15 mmol/L, and NT‐pro‐BNP was 28,900 pg/mL. The surface 12‐lead electrocardiogram (ECG) showed sinus rhythm at 60 bpm, PR interval 160 ms, QRS duration 115 ms, QT interval 460 ms, and left ventricular hypertrophy criteria. Negative T waves in leads I, II, aVL, and V₄–V₆ were also seen. In leads V₄–V₆, negative U waves were observed in concordance with negative T waves. In all precordial leads, beat‐to‐beat U‐wave polarity variability was observed as a polarity variation from negative to positive with associated and stable negative T waves, in a beat‐to‐beat alternate morphology.     

Characteristics of electrocardiographic repolarization in acute myocardial infarction complicated by ventricular fibrillation

Background and PurposeSome de- and re-polarization patterns can reflect an increased risk of ventricular tachyarrhythmias. We studied whether some electrocardiographic (ECG) patterns are able to predict the development of ventricular fibrillation (VF) during acute myocardial infarction (MI).MethodsWe compared the patterns of ST-T segment of 78 patients who developed VF during acute MI (patient with VF) vs 170 comparable patients with acute MI but with no VF complications.ResultsOf the VF group, 47 developed out-of-hospital VF and 31 developed VF after their admission to the hospital. A steep downsloping ST segment toward a negative T wave with or without a short, flat, or rising portion at the initial portion was observed in 69.2% of the 78 patients: 61.3% in patients with pre-VF and 74.5% in patients with post-VF, vs 9.4% of patients who did not develop VF (P < .0001). In 90.6% of the latter, a typical upward-concave or convex “ischemic” pattern of the ST segment was observed. Thus, the characteristic ST-T patterns were highly associated with VF with a specificity greater than 90%.ConclusionsA steep downsloping ST segment may characterize the ECGs of patients who develop VF during acute MI.     

Assessing the compatibility of primary human hepatocyte culture within porous silk sponges

Donor organ shortages have prompted the development of alternative implantable human liver tissues for patients suffering from end-stage liver failure. Purified silk proteins provide desirable features for generating implantable tissues, including sustainable sourcing from insects/arachnids, biocompatibility, tunable mechanical properties and degradation rates, and low immunogenicity upon implantation. While different cell types were previously cultured for weeks within silk-based scaffolds, it remains unclear whether such scaffolds can be used to culture primary human hepatocytes (PHH) isolated from livers. Therefore, here we assessed the compatibility of PHH culture within porous silk scaffolds that enable diffusion of oxygen/nutrients through the pores. We found that incorporation of type I collagen during the fabrication and/or autoclaving of porous silk scaffolds, as opposed to simple adsorption of collagen onto pre-fabricated silk scaffolds, was necessary to enable robust PHH attachment/function. Scaffolds with small pores (73 ± 25 μm) promoted larger PHH spheroids and consequently higher PHH functions than large pores (235 ± 84 μm) for at least 1 month in culture. Further incorporation of supportive fibroblasts into scaffolds enhanced PHH functions up to 5-fold relative to scaffolds with PHHs alone and 2D co-cultures on plastic. Lastly, encapsulating PHHs within protein hydrogels while housed in the silk scaffold led to higher functions than protein hydrogel-only or silk-only controls. In conclusion, porous silk scaffolds containing extracellular matrix proteins can be used for the culture of PHHs ± supportive non-parenchymal cells, which can be further built on in the future to create optimized silk-based liver tissue surrogates for cell-based therapy.

Porous silk scaffolds hybridized with extracellular matrix proteins are useful for culture of primary human hepatocytes ± supportive non-parenchymal cells.