Supplementation with hydrocortisone on the 3rd-5th day following dexamethasone premedicated chemotherapy eliminated severe dizziness and postural hypotension

We present the case of a 60 year-old woman with a stage III fallopian tube cancer submitted to hysterectomy and bilateral salpingo-oophorectomy with partial omenectomy, followed by six courses of chemotherapy and revision surgery. After each course of chemotherapy (paclitaxel + carboplatin) preceded by premedication with dexamethasone, she suffered from side- -effects, of which the most unpleasant was severe dizziness appearing on the third, fourth and fifth day following the listed combination of drugs. It was revealed that dizziness with concomitant sweating and rapid pulse, noted in the standing position, was combined with marked postural hypotension. Considering the possibility of a temporary pituitary-adrenal axis suppression caused by premedication with a very large dose of dexamethasone, during those three days she was supplemented with small doses of hydrocortisone, which caused almost complete disappearance of the mentioned symptoms. Our conclusion is that postural hypotension causing severe dizziness initially linked with chemotherapeutic drugs can be eliminated or markedly reduced by three days supplementation with hydrocortisone applied after the expected wash out of the dexamethasone.     

Right ventricular dysfunction and exercise capacity after inferior (posterior) wall acute myocardial infarction

Tissue Doppler echocardiography is a novel technique that can be used to diagnose right ventricular (RV) systolic dysfunction. Until recently, there have been no data on the influence of tissue Doppler-derived RV systolic dysfunction on exercise capacity after inferior (posterior) myocardial infarction (MI). We studied 90 consecutive patients (76% men, mean age 61 ± 10 years) with first inferior ST-segment elevation MI and left ventricular ejection fraction ≥45%. RV systolic dysfunction was defined as RV systolic myocardial velocity <11.5 cm/s at the basal segment of the RV free wall assessed by pulse tissue Doppler. Patients were categorized as with or without RV systolic dysfunction (RV systolic myocardial velocity 9.34 ± 1.36 and 13.74 ± 1.58 cm/s, respectively). A cardiopulmonary exercise test was performed before or soon after discharge (day 14 ± 10). Patients with RV systolic dysfunction had lower oxygen consumption assessed as percent predicted oxygen uptake in liters per minute and milliliters per kilogram per minute at their anaerobic threshold (61 ± 11% vs 69 ± 17%, p = 0.007; 53 ± 12% vs 61 ± 19%, p = 0.012, respectively) and at peak exercise (71 ± 12% vs 83 ± 16%, p = 0.0001; 62 ± 14% vs 74 ± 21%, p = 0.002, respectively). Multivariate regression analysis revealed that the following independent factors negatively influenced exercise capacity: RV systolic dysfunction, female gender, age, lower body mass index, current smoking, and maximal troponin I concentration. In conclusion, we found decreased exercise capacity in patients with systolic RV dysfunction assessed by pulse tissue Doppler in patients with inferior (posterior) wall acute MI despite preserved left ventricular function.     

Comprehensive investigation of genetic variation in the 8q24 region and multiple myeloma risk in the IMMEnSE consortium

Genome-wide association studies (GWAS) have shown that the 8q24 region harbours multiple independent cancer susceptibility loci, even though it is devoid of genes. Given that no GWAS data are currently available for multiple myeloma (MM), we tested the hypothesis that genetic variants in this region could play a role in MM risk. We genotyped 20 single nucleotide polymorphisms of 8q24 in 1188 MM cases and 2465 controls and found a statistically significant (P = 0·0022) association between rs2456449 and MM risk. These data provide further evidence that the genetic variability in the 8q24 region is associated with cancer risk, particularly haematological malignancies.     

Tumor location determines midkine level and its association with the disease progression in colorectal cancer patients: a pilot study

Purpose

The purpose of this study was to evaluate midkine, multipotential cytokine, and growth factor in colorectal cancer (CRC) stratified by tumor location.

Methods

Midkine was assessed immunoenzymatically in paired cancerous and noncancerous tissues from 53 CRCs and referred to CRC stage, tumor location, and size, and circulating cytokine levels.

Results

Midkine was higher in cancerous versus noncancerous tissue in 98?% cases (424.2 vs. 31.1?pg/mg, p?p?=?0.005) due to higher midkine level in noncancerous rectal than colonic tissue (45.5 vs. 26.2?pg/mg, p?=?0.074). Tumor location affected midkine association with CRC stage. Midkine fold change was higher in advanced stages of rectal cancers (16.8 vs. 5.3, respectively in III/IV vs. I/II, p?=?0.013), while it tended to be lower in colonic ones (25.3 vs. 47.8, p?=?0.134). In addition, fold change in midkine level was higher in rectal N1 than N0 cancers (17.3 vs. 16.5, p?=?0.032), while it tended to be lower in colonic cancers (23.6 vs. 50.1, p?=?0.085). Midkine negatively correlated with tumor size (r?=?0.40, p?=?0.017), while it tended to positively correlate with its serum levels (r?=?0.45, p?=?0.081).

Conclusions

Midkine is differently expressed in tumors arising from colonic and rectal mucosa, where it may play diverse roles in carcinogenesis. High midkine expression in noncancerous rectal mucosa might contribute to, a characteristic for rectal cancers, higher incidence of local recurrence. Divergent expression of midkine and its association pattern ought to be taken into account while designing midkine-directed therapies for CRC.     

Vitamin C modulates DNA damage induced by hydrogen peroxide in human colorectal adenocarcinoma cell lines (HT29) estimated by comet assay in vitro

Introduction

Cancer cells, compared to normal cells, are under increased oxidative stress associated with oncogenic transformation, alterations in metabolic activity, and increased generation of reactive oxygen species.

Material and methods

We investigated the ability of vitamin C to reduce the damage induced by hydrogen peroxide, in human colorectal adenocarcinoma cells in vitro by the comet assay. Additionally, we measured the kinetics and efficacy of the repair of DNA damage after incubation with vitamin C in the presence of H₂O₂.

Results

The obtained results showed that 1 h pre-incubation with vitamin C and exposure to H₂O₂ for the last 10 min of incubation caused a statistically significant (p < 0.05) increase in DNA migration in comet tails in all experimental series. For the 10 µM, 25 µM, 50 µM, 100 µM vitamin C concentrations the levels of DNA damage were as follows: 18.6%, 21.1%, 25.3% and 27.2%, respectively, as compared to the untreated cells (3.26%). However, in comparison with H₂O₂ alone (29.1%), we observed a statistically significant (p < 0.05) decrease of the genotoxic effect in HT29 cells induced by H₂O₂ for the two lowest of concentrations of vitamin C: 10 µM and 25 µM. The HT29 cells were able to achieve effective repair of the damaged DNA within 60 and 120 min after incubation with the tested compounds. All the values obtained in the test were statistically significant (p < 0.05).

Conclusions

Vitamin C caused a weaker DNA damaging effect of hydrogen peroxide and positively influences the level of oxidative DNA damage in HT29 cells (decrease ∼ 30%). We noted that DNA damage was effectively repaired during 120 min postincubation in the tested cells and that oxidative damage was the major type of damage.     

Maturational changes in connexin 43 expression in the seminiferous tubules may depend on thyroid hormone action

Introduction

Connexin 43 (Cx43) mediates the effect of thyroid hormone on Sertoli cell maturation in vitro. We investigated the influence of triiodothyronine (T3) administration on Cx43 expression in relation to the progress in seminiferous tubule maturation.

Material and methods

Male rats were daily injected with 100 µg T3/kg body weight from birth until postnatal day (pnd) 5 (transient treatment – tT3) or until pnd 15 (continuous treatment – cT3) or solvent – control (C). On pnd 16 serum hormone levels, body and testes weight, seminiferous tubule morphometry, Cx43 immunostaining and germ cell degeneration were investigated. Cx43 expression was also assessed in six 50-day-old adult untreated rats.

Result

tT3 increased 2.6-fold serum level of T3, testes weight, and seminiferous tubule diameter, and induced maturation-like dislocation of Cx43 expression from the apical to the peripheral region of Sertoli cell cytoplasm. In addition, incidence of Cx43-positive tubules declined from 86% in C to 46% after tT3, being similar to the adult value (30% of tubules Cx43-positive). In turn, cT3 increased serum T3 level 12-fold, and decreased body weight. Seminiferous tubules became shortened and distended, Sertoli cell cytoplasm vacuolated, Cx43 expression had minimal intensity and germ cell degeneration increased.

Conclusions

Cx43 might intermediate a short and transient stimulatory effect of T3 on seminiferous tubule maturation that disappeared together with exposure to the toxic effect of a continuously high level of the hormone.     

Association of CD36 gene polymorphisms with echo- and electrocardiographic parameters in patients with early onset coronary artery disease

Introduction

CD36 plays an important role in long-chain fatty acid homeostasis in skeletal muscle and the myocardium. CD36 deficiency may lead to reduced myocardial uptake of long-chain fatty acid. Therefore, different mutations of the CD36 gene may contribute to the clinical heterogeneity of cardiac hypertrophy.

Material and methods

The objective of the study was to investigate whether there is an association between the sequence changes in CD36 and echocardiographic and electrocardiographic parameters in Caucasian patients with early onset coronary artery disease. The study group comprised 100 patients. Electrocardiography and echocardiography were performed in all patients. Amplicons of exons 4 to 6 including fragments of introns were studied using the denaturing high-performance liquid chromatography technique.

Results

IVS3-6TC (rs3173798) heterozygotes had impaired left ventricle diastolic function. 573GA heterozygotes (rs5956) had higher frequency of pseudonormal left ventricular diastolic function and it was confirmed by the increase in wave A’ in the tissue Doppler. 591AT genotype was associated with borderline higher posterior wall end-diastolic thickness and lower E/A ratio. These results are consistent with electrocardiography parameters which could reflect left ventricular hypertrophy (higher R_V5(6) and R_V5(6) + S_V1(2) parameters, depressed ST segments and tendency to longer Qtc II interval) in 591AT heterozygotes.

Conclusions

Detected variant alleles of CD36 may be associated with features of left ventricular hypertrophy and impaired diastolic function.