Clinical trials update from the European Society of Cardiology Heart Failure meeting and the American College of Cardiology: darbepoetin alfa study, ECHOS, and ASCOT-BPLA

This article provides information and a commentary on landmark trials presented at the European Society of Cardiology Heart Failure meeting held in June 2005, relevant to the pathophysiology, prevention and treatment of heart failure. All reports should be considered as preliminary data, as analyses may change in the final publication. The erythropoiesis stimulating protein, darbepoetin alfa, increased haemoglobin levels, improved quality of life and showed a trend for improved exercise duration in anaemic patients with symptomatic chronic heart failure. In the ECHOS study, the selective dopamine agonist nolomirole (CHF1035) showed no benefit in heart failure patients. Preliminary results of the ASCOT-BPLA study, which were reported at the American College of Cardiology meeting in March 2005, showed that in hypertensive patients, treatment with a calcium antagonist plus an ACE inhibitor was more effective at reducing cardiovascular outcomes than atenolol plus a diuretic.     

Branching out: a molecular fingerprint of endothelial differentiation into tube-like structures generated by Affymetrix oligonucleotide arrays

The process of endothelial differentiation into a network of tube-like structures with patent lumens requires an integrated program of gene expression. To identify genes upregulated in endothelial cells during the process of tube formation, RNA was prepared from several different time points (0, 4, 8, 24, 40, and 48 hours) and from three different experimental models of human endothelial tube formation: in collagen gels and fibrin gels driven by the combination of PMA (80), bFGF (40 ng/ml) and bFGF (40 ng/ml) or in collagen gels driven by the combination of HGF (40 ng/ml) and VEGF (40 ng/ml). Gene expression was evaluated using Affymetrix Gene Chip oligonucleotide arrays. Over 1000 common genes were upregulated greater than twofold over baseline at one or more time points in the three different models. In the present study, we discuss the identified genes that could be assigned to major functional classes: apoptosis, cytoskeleton, proteases, matrix, and matrix turnover, pumps and transporters, membrane lipid turnover, and junctional molecules or adhesion proteins.     

To study the clinical efficacy and nephrotoxicity along with the risk factors for acute kidney injury associated with parenteral polymyxin B

Aim:

The aim of this study was to evaluate the clinical efficacy and nephrotoxicity along with the risk factors for acute kidney injury (AKI) associated with the parenteral polymyxin B in patients with the multidrug resistance (MDR) gram −ve infections in a tertiary Intensive care unit (ICU).

Materials and Methods:

A retrospective cohort study (March 2010-October 2011) was conducted in Medical ICU of a 23 bedded tertiary care hospital in Northern India.

Results:

Out of 71 ICU patients who were administered polymyxin B, only 32 (M:F = 1:0.8) met the inclusion criteria. Patients with concurrent administration of nephrotoxic drugs were excluded from the study. Mean age of patients was 48.53 ± 13.90 years ranging from 16 years to 68 years. 6 out of 32 (18.7%) patients progressed to AKI, whereas renal functions remained normal in 26 (81.2%) patients. No statistically significant difference was observed in mortality between AKI and non AKI patients at the end of therapy (33.3% vs. 26.9%, P value 0.756). Older age (62.33 ± 11.90 vs. 45.34 ± 2.45, P value 0.005) was found to be an independent risk factor for causing nephrotoxicity.

Conclusion:

In the present scenario of rising infections with MDR gram −ve micro-organisms, this pilot study suggests that polymyxin B can be used effectively and safely in patients not receiving other nephrotoxic drugs, with cautious administration in older patients as they are more vulnerable to nephrotoxicity caused by polymyxin B.     

Acute stress-induced neuronal plasticity in the corticoid complex of 15-day-old chick,Gallus domesticus

Several studies conducted on chicken have shown that a single stress exposure may impair or improve memory as well as learning processes. However, to date, stress effects on neuronal morphology are poorly investigated wherefore it was of interest to evaluate this further in chicks. Thus, the present study aims to investigate the role of single acute stress (AS) of 24 h food and water deprivation in neuronal plasticity in terms of spine density of the corticoid complex (CC) in 15-day-old chick, Gallus domesticus, by using three neurohistological techniques: Cresyl Violet, Golgi Colonnier, and Golgi Cox technique. The dorsolateral surface of the cerebral hemisphere is occupied by CC which can be differentiated into two subfields: an intermediate corticoid (CI) subfield (arranged in layers) and a dorsolateral corticoid (CDL) subfield. Based on different criteria such as soma shape, dendritic branching pattern, and dendritic spine density, two main moderately spinous groups of neuronal cells were observed in the CC, namely, projection neurons (comprising of multipolar and pyramidal neurons) and stellate neurons. In the present study, the stellate neurons have shown a significant decrease as well as an increase in their spine density in both CI and CDL subfields, whereas the multipolar neurons had shown a significant increase in their spine density in the CDL region only. The present study shows that AS induces neuronal plasticity in terms of spine density in both CI and CDL neurons. The morphological changes in the form of decreased dendritic branches due to stress have been observed in the CI region in comparison to CDL region, which could be linked to more effect of stress in this region. The avian CDL corresponds to the entorhinal cortex of mammals on the basis of neuronal morphology and bidirectional connections between adjacent areas. The projection neurons increase their branches and also their spine number to cope with the stress effects, while the stellate neurons show contrasting effect in their spine density. Therefore, this study will establish that slight modifications in natural stimuli or environmental changes faced by the animal may affect their dorsolateral forebrain which shows neuronal plasticity that help in the development of an adaptive capacity of the animal to survive under changing environmental conditions.     

Histomorphological Patterns of Endometrium in Infertility

Background

Endometrium is the most sensitive indicator of ovarian function and endometrial biopsy is one of the most important investigations in infertility. The current study was carried out to investigate the histomorphological patterns of endometrium in infertile women and to compare the results with other similar studies.

Materials and Methods

A cross-sectional study on 2,080 infertile women was carried out to find the incidence of various histomorphological patterns in hematoxylin-eosin stained sections of endometrium and compare them with other Indian studies.

Results

In the current study majority of cases (88.50 %) were of primary infertility; the highest number of cases was in the age group of 21–30 years and the oldest patient was of 50 years age. The various abnormalities observed were anovulatory endometrium (15.75 %), inadequate proliferative (1.90 %), inadequate secretory (9.52 %), glandulo-stromal disparity (GSD) (4.21 %), hyperplasia (1.10 %), and endometritis (1.63 %). In 3.0 % cases menstrual cycle history was not available and curettage was done at inappropriate period of the cycle in 11.63 %. Comparison with other studies revealed the results matching with some and differing with others.

Conclusion

In the current study, anovulatory endometrium and luteal phase defect are the major causes of infertility, and tuberculous endometritis, non-specific endometritis and GSD are minor contributing factors. These are treatable causes. Premenstrual endometrial biopsy, if accompanied by information of menstrual cycle and date of biopsy, can be a very reliable diagnostic tool for hormonal dysfunction and intrinsic endometrial factors in infertility.