Vascular compression of rostral medulla oblongata: prospective MR imaging study in hypertensive and normotensive subjects

PURPOSE: To prospectively evaluate prevalence of neurovascular contacts (NVCs) at the rostral medulla oblongata in normotensive and hypertensive subjects. MATERIALS AND METHODS: Forty-three patients with severe essential hypertension and 45 normotensive subjects were matched for age, sex, and body mass index. Magnetic resonance (MR) imaging included transverse and coronal T2-weighted turbo spin-echo (section thickness, 3.0 mm), transverse three-dimensional (3D) time-of-flight MR angiographic (section thickness, 0.8 mm), and 3D constructive interference in steady state (CISS) (section thickness, 1.0 mm) sequences. All MR images were reviewed by two radiologists who were blinded to the hypertensive status of subjects. Presence and degree of NVC at rostral medulla and left/right rostral ventrolateral medulla (RVLM) were evaluated together with conspicuity of anatomic structures on MR images. Differences in prevalence of NVC among normotensive and hypertensive subjects were tested for statistical significance (P <.05) by using nonparametric tests. RESULTS: Among hypertensive patients, 34 (79%) of 43 showed NVC of rostral medulla at any location, and 14 (33%) of 43 had NVC at the left RVLM. In controls (normotensive subjects), 35 (78%) of 45 showed NVC of rostral medulla, and 17 (38%) of 45 had NVC at left RVLM. Prevalence of NVC was not significantly different between both groups at any location of rostral medulla. Compared with T2-weighted turbo spin-echo and 3D time-of-flight MR imaging sequences, 3D CISS offered better contrast resolution of neural and vascular structures and superior delineation of outer vascular contours. CONCLUSION: Vascular compression of the rostral medulla oblongata is a frequent finding in both hypertensive and normotensive subjects. Results of this study do not support NVC at left RVLM as an etiologic factor in essential hypertension.     

Longitudinal changes in pituitary-adrenal hormones in South African women with burnout

The author’ goal was to document baseline pituitaryadrenal hormonal and related metabolic variables in 16 female patients with burnout. Then, following stress management intervention, to compare the changes with an equal number of untreated control subjects. At monthly intervals for 4 mo, 24-h urine samples were obtained for determination of free cortisol excretion. In addition, fasting blood samples were analyzed for levels of cortisol, dehydroepiandrosterone sulfate (DHEAS), ACTH, aldosterone, and catecholamines. Other biochemical measurements included growth hormone, prolactin, insulin, glucose, and lipid components. The Maslach Burnout Inventory, General Health Questionnaire-28, and Zung depression rating scale were completed on each consecutive visit. The most striking finding was the reduction of urine free-cortisol excretion in the patients compared with controls. Initial urinary free cortisol was significantly lower in the patients (mean ± SEM=47.2 ± 11.0 vs 79.0 ± 6.8 nmol/L, P=0.02) and remained significantly reduced at 4 mo (mean ± SEM=44.0 ± 6.1 vs 91.1 ± 8.8 nmol/L, p=0.0001). There were no significant changes in the other hormonal and biochemical data. We conclude that there is functional hypocortisolism in burnout, which is not immediately restored on stress management intervention despite clinical and psychological improvement.     

Metabolomics in pancreatic cancer biomarkers research

Pancreatic cancer is one of the worst prognoses of all malignancies. More than 40,000 deaths a year from this disease are observed in European Union alone. The only possibly curative treatment of pancreatic cancer is surgery, yet only 15–20% of patients have operable disease and even patients, which go through surgery and adjuvant chemotherapy, survival is less than 30%. The sensitive and specific biomarkers which could be used for the advance of early diagnostics are needed and constantly researched. Metabolomics is a technology which analyzes the concentrations of low-molecular-weight metabolites (the metabolome) has lately effectively developed due to the improvements in analytical technology. Metabolome analysis can be a one of the useful approaches for the biomarker discovery and disease diagnosis. Here we discuss recent discoveries in the field of pancreatic cancer metabolomics as well as the most promising biomarkers for diagnostics, prognosis and prediction.     

Deceitful dissimulation of dyspnoea

We present a case of a young woman, who was examined for polymorphic complaints. Life-threatening complications during a standard treatment occurred, because of severe left ventricular dysfunction caused by an incessant atrial tachycardia and subsequent tachycardia induced cardiomyopathy. The only symptom reflecting the serious diagnosis was a mild dyspnoea on exertion. Because of patient's dissimulation, this symptom was uncovered late. Focal atrial tachycardia was successfully treated with catheter ablation and the treatment resulted in normalization of the left ventricular systolic function in three months.     

LOX/COX inhibitors enhance the antineoplastic effects of all-trans retinoic acid in osteosarcoma cell lines

The induced differentiation of tumor cells into mature phenotypes is a promising strategy in cancer therapy. In this study, the effects of combined treatment with all-trans retinoic acid (ATRA) and lipoxygenase/cyclooxygenase inhibitors were examined in two osteosarcoma cell lines, Saos-2 and OSA-01. Caffeic acid and celecoxib were used as inhibitors of 5-lipoxygenase and of cyclooxygenase-2, respectively. Changes in the cell proliferation, matrix mineralization, and occurrence of differentiation markers were evaluated in treated cell populations at intervals. The results confirmed the capability of caffeic acid to enhance the antiproliferative effect of ATRA in both cell lines. In contrast, celecoxib showed the same effect in Saos-2 cells only. Furthermore, the extension of matrix mineralization was observed after combined treatment with ATRA and celecoxib or caffeic acid. The increased expression of osteogenic differentiation markers was observed in both cell lines after the combined application of ATRA and inhibitors. The obtained results clearly demonstrate the capability of lipoxygenase/cyclooxygenase inhibitors to enhance the antiproliferative and differentiating effect of ATRA in osteosarcoma cells, although some of these effects are specific and depend on the biological features of the respective tumor or cell line.     

Five Antigen Tests for SARS-CoV-2: Virus Viability Matters

Antigen testing for SARS-CoV-2 (AGT) is generally considered inferior to RT-PCR testing in terms of sensitivity. However, little is known about the infectiousness of RT-PCR positive patients who pass undetected by AGT. In a screening setting for mildly symptomatic or asymptomatic patients with high COVID-19 prevalence (30–40%), 1141 patients were tested using one of five AGTs and RT-PCR. Where the results differed, virus viability in the samples was tested on cell culture (CV-1 cells). The test battery included AGTs by JOYSBIO, Assure Tech, SD Biosensor, VivaChek Biotech and NDFOS. Sensitivities of the ATGs compared to RT-PCR ranged from 42% to 76%. The best test yielded a 76% sensitivity, 97% specificity, 92% positive, and 89% negative predictive values, respectively. However, in the best performing ATG tests, almost 90% of samples with “false negative” AGT results contained no viable virus. Corrected on the virus viability, sensitivities grew to 81–97% and, with one exception, the tests yielded high specificities >96%. Performance characteristics of the best test after adjustment were 96% sensitivity, 97% specificity, 92% positive, and 99% negative predictive values (high prevalence population). We, therefore, believe that virus viability should be considered when assessing the AGT performance. Also, our results indicate that a well-performing antigen test could in a high-prevalence setting serve as an excellent tool for identifying patients shedding viable virus. We also propose that the high proportion of RT-PCR-positive samples containing no viable virus in the group of “false negatives” of the antigen test should be further investigated with the aim of possibly preventing needless isolation of such patients.     

Vasoactive systems in L-NAME hypertension: the role of inducible nitric oxide synthase

OBJECTIVES: The contribution of the renin-angiotensin system (RAS) and the sympathetic nervous system (SNS) to blood pressure (BP) maintenance was evaluated in rats with N(omega)-nitro-L-arginine methyl ester (L-NAME) hypertension. Furthermore, we studied the extent of nitric oxide (NO) synthesis inhibition and the participation of remaining NO in the counterbalance of pressor systems, with a special reference to inducible nitric oxide synthase (iNOS). METHODS: Wistar rats subjected to chronic L-NAME treatment (40 mg/kg per day for 4 weeks) were used. A consecutive blockade of RAS (captopril) and SNS (pentolinium) was followed by acute L-NAME injection. Dimethylguanidine or aminoguanidine were used to affect NO synthesis by iNOS. RESULTS: L-NAME hypertensive rats had borderline augmentation of depressor response to captopril injection, but their BP fall after pentolinium was considerably enhanced compared with controls. Residual BP (recorded after simultaneous blockade of the RAS and the SNS) was elevated by 20-40% in hypertensive rats. Pronounced inhibition of NO synthase activity (50% reduction in the aorta and myocardium) was detected in L-NAME hypertensive rats in which the BP rise elicited by acute L-NAME injection was considerably attenuated (by 60-80%). In contrast, acute administration of dimethylguanidine [mixed endothelial NO synthase (eNOS)/iNOS inhibitor] to hypertensive rats induced a major BP rise similar to that caused by L-NAME injection in controls. Aminoguanidine (a selective iNOS inhibitor) caused a substantial BP rise in L-NAME hypertensive rats only. CONCLUSION: The contribution of SNS to BP maintenance in L-NAME hypertension is more important than that of RAS. In L-NAME hypertensive rats the iNOS becomes a major source of hemodynamically important NO production, which is still insufficient to compensate prevailing vasoconstriction.     

Combined right ventricular systolic and diastolic dysfunction represents a strong determinant of poor prognosis in patients with symptomatic heart failure

BACKGROUND: The presence of right ventricular systolic dysfunction is known to significantly worsen prognosis of patients with heart failure. However, the prognostic impact of right ventricular diastolic dysfunction and of its combination with right ventricular systolic dysfunction and with other prognostic markers has not yet been systematically studied. The aim of this study was to assess the prognostic impact of combined right ventricular systolic and diastolic dysfunction in patients with symptomatic heart failure due to ischemic or idiopathic dilated cardiomyopathy. METHODS: The study included 177 consecutive patients with symptomatic heart failure (mean left ventricular ejection fraction of 23%). All patients underwent clinical and laboratory examination, standard echocardiography completed by Doppler tissue imaging of the tricuspid annular motion, and right-sided heart catheterization. They were followed up for a mean period of 16 months (range, 1-48 months). RESULTS: During the follow-up, there were 28 cardiac-related deaths and 35 non-fatal cardiac events (31 hospitalizations for heart failure decompensation and 4 hospitalizations for malignant arrhythmias requiring the implantation of a cardioverter-defibrillator). The multivariate stepwise Cox regression modeling revealed the right ventricular systolic (represented by the peak systolic tricuspid annular velocity-Sa) and diastolic (represented by the peak early diastolic tricuspid annular velocity-Ea) function to be the independent predictors of event-free survival or survival (p<0.01). The Sa separated better between patients with and without the risk of cardiac events (p<0.05), while the Ea appeared to further distinguish patients with increased risk (those at risk of late event from those at risk of early non-fatal event and early death). The strongest predictive information was obtained by the combination of Sa and Ea creating the Sa/Ea categories. The Sa/Ea I category of patients (Sa>or=10.8 cm s(-1) and Ea>or=8.9 cm s(-1)) had excellent prognosis. On the other hand, the Sa/Ea IV category (Sa<10.8 cm s(-1) and Ea<8.9 cm s(-1)) was found to be at a very high risk of cardiac events (p<0.001 vs. Sa/Ea I). Imbalanced categories of patients (Sa/Ea II and III) with only one component (Sa or Ea) pathologically decreased were at medium risk when assessing event-free survival. However, a significantly better survival (p<0.05) was found in patients with Ea>or=8.9 cm s(-1) (Sa/Ea I and III categories) as compared with those having Ea<8.9 cm s(-1) (Sa/Ea II and IV categories). Thus, in contrast to event-free survival, the survival pattern was determined mainly by the Ea value with only little additional contribution of Sa. CONCLUSIONS: The assessment of right ventricular systolic and diastolic function provides complementary information with a very high power to stratify prognosis of patients with heart failure. The combination of right ventricular systolic and diastolic dysfunction identifies those with a very poor prognosis.     

Disordered follicle development in ovaries of prenatally androgenized ewes

Exposure to excess androgens in utero induces irreversible changes in gonadotrophin secretion and results in disrupted reproductive endocrine and ovarian function in adulthood, in a manner reminiscent of the common clinical endocrinopathy of polycystic ovary syndrome (PCOS). We have recently identified an abnormality in early follicle development in PCOS which we suggested might be an androgenic effect. We propose that altered ovarian function in androgenized ewes is due to prenatal androgens not only causing an abnormality of gonadotrophin secretion, but also exerting a direct effect on the early stages of folliculogenesis. Therefore, in this study, we explored the possible differences between small preantral follicles in the ovarian cortex of androgenized female lambs with those of normal lambs. At 8 months of age, small ovarian cortical biopsies (approximately 5 mm3) were obtained at laparotomy from nine female lambs that had been exposed to androgens in utero from embryonic days 30 to 90 of a 147-day pregnancy, and 11 control female lambs. Further, ovarian tissue was obtained at 20 months of age from ten androgenized and nine control animals. Tissue was either fixed immediately for histology or cultured for up to 15 days prior to fixing. The number of follicles in haematoxylin and eosin-stained sections was counted and recorded along with the stage of development. Before culture, the total follicle density (follicles/mm3 tissue) was not statistically significantly different between the two types of ovary at either 8 or 20 months of age. Furthermore, there were no statistically significant differences in the density of follicles at each stage of development. However, there was a lower percentage of primordial follicles, but a higher percentage of primary follicles, in biopsies taken at 8 months from androgenized lambs when compared with controls. At 20 months, the proportions of follicles at the primordial and primary stages were not significantly different between the two groups, but this was mainly attributable to an increase in the proportion of growing follicles in biopsies from control animals. Culture of ovarian cortex from 8-month-old lambs resulted in a progressive increase in the proportion of growing follicles when compared with tissue fixed on the day of surgery. However, there was no difference between androgenized and control tissue in the percentage of growing follicles. The increase in the proportion of growing follicles in the cortex of androgenized animals is reminiscent of similar observations in human polycystic ovaries and suggests that excess exposure to androgen in early life plays a part in the accelerated progression of follicle development from the primordial to the primary stage in polycystic ovaries.