A case representing coexistence of acute myeloblastic leukemia and dedifferentiated liposarcoma: the possible role of chemotherapy in triggering dedifferentiation

Acute myelogenous leukemia (AML) is a hematological disorder that is characterized by an abnormal proliferation of immature myeloid cells. Dedifferentiated and well-differentiated liposarcomas are the two pathological subtypes of liposarcoma, based on the WHO classification. Transition from well-differentiated to dedifferentiated liposarcoma is a well-recognized phenomenon. Well-differentiated tumors are known to have low malignancy grade. However, when dedifferentiation occurs, the tumor acquires the aggressive features of a fully malignant lesion. This process largely is believed to progress in a time-dependant manner; however, time is not the only factor of importance. The potential roles of other factors in this transition are still unclear. To date, the coexistence of AML and liposarcoma has not been reported in the literature. In this paper, we report on a case of coexistence of AML and liposarcoma, and on the unusual behavior of a well-differentiated tumor after dedifferentiation occurs.     

Chlamydia pneumoniae is an important cause of community-acquired pneumonia in school-aged children: serological results of a prospective, population-based study.

The aetiology of community-acquired pneumonia in childhood was studied in the total population of 8851 children in the area of 4 municipalities in eastern Finland. All cases of community-acquired pneumonia (n = 201) were registered during a surveillance period of 12 months between September 1, 1981 and August 31, 1982. The diagnosis of pneumonia was verified radiologically in all identified cases. The diagnosis of chlamydial infection was based on an antibody response measured by complement fixation (CF), by enzyme immunoassay (EIA; IgG or IgM) or by microimmunofluorescence (MIF; IgG or IgM), and the diagnosis of mycoplasmal infection on CF alone. In total, 29 cases of Chlamydia sp. infection were diagnosed; 20 were caused by Chlamydia pneumoniae. Thus, C. pneumoniae was an aetiological agent in 10%, of the 201 pneumonia cases: the proportion was 9% for children aged 5-9 y and 31% for those aged 10 y or more. In the study population, the total incidence of C. pneumoniae pneumonia was 2.3/1000/y. Mycoplasma pneumoniae serology (CF) was positive in 44 patients (22%); the total incidence of M. pneumoniae pneumonia was 5.0/1000/y. Serological evidence of both Chlamydiae and M. pneumoniae was detected in 9 (41%) patients. Our results indicate that C. pneumoniae is an important cause of community-acquired pneumonia in school-aged children. Diagnostic serological response to Chlamydia species or M. pneumoniae was found in 42% of pneumonia patients between 5 and 9 y of age and in 67% of patients aged 10 y or more. Thus, we suggest that macrolides should be considered as an empirical antimicrobial treatment for community-acquired pneumonia, especially in school-aged outpatients.     

Familial clustering of beta-cell autoimmunity in initially non-diabetic children

BACKGROUND: Type 1 diabetes is characterised by familial aggregation. We set out to explore whether beta-cell autoimmunity, which is considered to precede clinical disease, also shows familial clustering. METHODS: Tests for HLA DQB1 alleles (*02, *0301, *0302, *0602) and islet cell autoantibodies (ICA) were performed on 5836 children from 2283 families. When a child tested positive for ICA, all his/her previous or subsequent samples that were available were also tested for insulin autoantibodies (IAA), antibodies to glutamic acid decarboxylase (GADA) and antibodies to the IA-2 protein (IA-2A). RESULTS: Forty-four families were observed to have two or more children positive for at least ICA. This proportion (1.9%) was almost five times higher than expected (0.4%; p < 0.001). The frequency of multiple (>/=2) autoantibodies also showed familial aggregation, the observed proportion (0.39%) being three times that expected (0.13%; p < 0.001). In 72.7% of the families with at least two ICA-positive siblings, the children with autoantibodies had the same HLA DQB1 genotype. The median age difference between the ICA-positive children within the same family was 3.3 years (range 0.0-10.5 years), and the median time interval in the appearance of ICA within the family was 1.6 years (range 0.0-3.2). CONCLUSIONS: beta-cell autoimmunity, as defined by the appearance of ICA, demonstrates familial aggregation, although the antibodies do not appear in close temporal proximity or at an identical age within the same family. The HLA-DQB1 genotypes are more often identical in siblings with autoantibodies than in other siblings.     

Variation in the use of renal replacement therapy in patients with septic shock: a substudy of the prospective multicenter observational FINNAKI study

Introduction

Indications for renal replacement therapy (RRT) have not been generally standardized and vary among intensive care units (ICUs). We aimed to assess the proportion, indications, and modality of RRT, as well as the association between the proportion of RRT use and 90-day mortality in patients with septic shock in Finnish adult ICUs.

Methods

We identified patients with septic shock from the prospective observational multicenter FINNAKI study conducted between 1 September 2011 and 1 February 2012. We divided the ICUs into high-RRT and low-RRT ICUs according to the median of the proportion of RRT-treated patients with septic shock. Differences in indications, and modality of RRT between ICU groups were assessed. Finally, we performed an adjusted logistic regression analysis to evaluate the possible association of the ICU group (high vs. low-RRT) with 90-day mortality.

Results

Of the 726 patients with septic shock, 131 (18.0%, 95% CI 15.2 to 20.9%) were treated with RRT. The proportion of RRT-treated patients varied from 3% up to 36% (median 19%) among ICUs. High-RRT ICUs included nine ICUs (354 patients) and low-RRT ICUs eight ICUs (372 patients). In the high-RRT ICUs patients with septic shock were older (P = 0.04), had more cardiovascular (P <0.001) and renal failures (P = 0.003) on the first day in the ICU, were more often mechanically ventilated, and received higher maximum doses of norepinephrine (0.25 μg/kg/min vs. 0.18 μg/kg/min, P <0.001) than in the low-RRT ICUs. No significant differences in indications for or modality of RRT existed between the ICU groups. The crude 90-day mortality rate for patients with septic shock was 36.2% (95% CI 31.1 to 41.3%) in the high-RRT ICUs compared to 33.9% (95% CI 29.0 to 38.8%) in the low-RRT ICUs, P = 0.5. In an adjusted logistic regression analysis the ICU group (high-RRT or low-RRT ICUs) was not associated with 90-day mortality.

Conclusions

Patients with septic shock in ICUs with a high proportion of RRT had more severe organ dysfunctions and received more organ-supportive treatments. Importantly, the ICU group (high-RRT or low-RRT group) was not associated with 90-day mortality.     

Cortisol levels during an oral glucose tolerance test in lean and obese women

Because of the similarities between Cushing's syndrome and insulin resistance syndrome,cortisol metabolism in obesity has been investigated in numerous studies. Our study investigates serum glucose, insulin, and cortisol response to oral glucose stimulation in a group of obese and lean normotensive, normolipidemic, and glucose-tolerant premenopausal women. Twenty-one obese [body mass index (BMI) 37Z +/- 6.3 kg/m2) and 14 lean (BMI: 21.5 +/- 1.0 kg/m2) age-matched healthy premenopausal women were included in the study. Serum glucose, insulin, and cortisol levels were measured at 30-minute intervals during 120 minutes of oral glucose tolerance testing (OGTT). Mean serum glucose and insulin levels were significantly higher in the obese group compared with lean subjects, and cortisol levels were similar during OGTT. There was not a significant difference for cortisol area under the curve (AUC) during OGTT between the two groups. No correlation between cortisol AUC, insulin AUC, and glucose AUC was noted for both groups. During OGTT, a decrease in cortisol levels was observed in both groups. The decrement occurred at 30 minutes of the OGTT in the obese group and at 60 minutes of the OGTT in the lean group. At 90 and 120 minutes of the OGTT, serum cortisol levels were similar to basal levels in both the obese group and the lean group. Previous studies reported altered hypotalamic-pituitary-adrenal axis activity, altered levels of urinary cortisol excretion, and increased metabolic clearance of cortisol in obesity. In our study in obese women, the only detected difference from lean subjects was a quicker suppression and recovery in serum cortisol levels after glucose administration.     

Pharmacophore modelling of 17beta-HSD1 enzyme based on active inhibitors and enzyme structure

The 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) enzyme regulates the conversion of estrone (E1) to the biologically active estradiol (E2). Due to its role as a key enzyme in female hormone production, it has emerged as an attractive drug target for inhibitor development in relation to hormone-dependent breast cancer. Herein, we report four pharmacophore models of 17beta-HSD1 based on a crystal structure, a relaxed crystal structure, a library of 17beta-HSD1 inhibitors and on a docked complex of 17betaHSD1 enzyme and a potent inhibitor. The models were used in screening two databases, which produced novel compounds to be used as leads in our drug design project. The results were validated by docking the compounds to the active site of the 17beta-HSD1 enzyme. With the help of our 3D-QSAR model, these results will be used to develop new inhibitors of 17beta-HSD1 as drug candidates.     

Late gadolinium enhanced cardiovascular magnetic resonance of lamin A/C gene mutation related dilated cardiomyopathy

Background

The purpose of this study was to identify early features of lamin A/C gene mutation related dilated cardiomyopathy (DCM) with cardiovascular magnetic resonance (CMR). We characterise myocardial and functional findings in carriers of lamin A/C mutation to facilitate the recognition of these patients using this method. We also investigated the connection between myocardial fibrosis and conduction abnormalities.

Methods

Seventeen lamin A/C mutation carriers underwent CMR. Late gadolinium enhancement (LGE) and cine images were performed to evaluate myocardial fibrosis, regional wall motion, longitudinal myocardial function, global function and volumetry of both ventricles. The location, pattern and extent of enhancement in the left ventricle (LV) myocardium were visually estimated.

Results

Patients had LV myocardial fibrosis in 88% of cases. Segmental wall motion abnormalities correlated strongly with the degree of enhancement. Myocardial enhancement was associated with conduction abnormalities. Sixty-nine percent of our asymptomatic or mildly symptomatic patients showed mild ventricular dilatation, systolic failure or both in global ventricular analysis. Decreased longitudinal systolic LV function was observed in 53% of patients.

Conclusions

Cardiac conduction abnormalities, mildly dilated LV and depressed systolic dysfunction are common in DCM caused by a lamin A/C gene mutation. However, other cardiac diseases may produce similar symptoms. CMR is an accurate tool to determine the typical cardiac involvement in lamin A/C cardiomyopathy and may help to initiate early treatment in this malignant familiar form of DCM.     

Fetal Alcohol Effects: Mechanisms and Treatment

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chair was Edward P. Riley. The presentations were (1) Does alcohol withdrawal contribute to fetal alcohol effects? by Jennifer D. Thomas and Edward P. Riley; (2) Brain damage and neuroplasticity in an animal model of binge alcohol exposure during the third trimester equivalent, by Charles R. Goodlett, Anna Y. Klintsova, and William T. Greenough; (3) Ganglioside GM1 reduces fetal alcohol effects, by Basalingappa L. Hungund; and (4) Fetal alcohol exposure alters the wiring of serotonin system at mid-gestation, by F. Zhou, Y. Sari, Charles Goodlett, T. Powrozek, and Ting-Kai Li.