Organs at risk's tolerance and dose limits for head and neck cancer re-irradiation: A literature review.

Re-irradiation is becoming an established treatment option for recurrent or second primary head and neck cancer(HNC). However, acute and long-term RT-related toxicities could dramatically impact patients' quality of life. Due to the sparse literature regarding HNC re-irradiation, data on tolerance doses for various organs at risk (OARs) are scarce. Our aim was to systematically review the clinical literature regarding HNC re-irradiation, focusing on treatment toxicity, OARs tolerance, and dose limit recommendations. Thirty-nine studies (three randomized, five prospective, 31 retrospective) including 3766 patients were selected. The median interval time between the first course and re-irradiation was 28  months (range, 6-90). In 1043 (27.6%) patients, postoperative re-irradiation was performed. Re-irradiation doses ranged from 30 Gy in 3 fractions using stereotactic technique to 72 Gy in conventional fractionation using intensity-modulated radiotherapy. Pooled acute and late toxicityrates ≥G3 were 32% and 29.3%, respectively. The most common grade 3-4 toxic effects were radionecrosis, dysphagia requiring feeding tube placement and trismus. In 156 (4.1%) patients, carotid blowout was reported. Recommendations for limiting toxicity included the time interval between radiation treatments, the fractionation schedules, and the re-irradiation treatment volumes. Cumulative dose limit suggestions were found and discussed for the carotid arteries, temporal lobes, and mandible.

Lipid Profile Changes Induced by Chronic Administration of Anabolic Androgenic Steroids and Taurine in Rats.

Background and Objectives: Anabolic androgenic steroids (AAS), used as a therapy in various diseases and abused in sports, are atherogenic in supraphysiological administration, altering the plasma lipid profile. Taurine, a conditionally-essential amino acid often used in dietary supplements, was acknowledged to delay the onset and progression of atherogenesis, and to mitigate hyperlipidemia. The aim of the present study was to verify if taurine could prevent the alterations induced by concomitant chronic administration of high doses of AAS nandrolone decanoate (DECA) in rats. Materials and Methods: Thirty-two male Wistar rats, assigned to 4 equal groups, were treated for 12 weeks either with DECA (A group), taurine (T group), both DECA and taurine (AT group) or vehicle (C group). Plasma triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), hepatic triglycerides (TGh) and liver non-esterified fatty acids (NEFA) were then determined. Results: DECA elevated TG level in A group vs. control (p = 0.01), an increase prevented by taurine association in AT group (p = 0.04). DECA decreased HDL-C in A group vs. control (p = 0.02), while taurine tended to increase it in AT group. DECA decreased TGh (p = 0.02) in A group vs. control. Taurine decreased TGh in T (p = 0.004) and AT (p < 0.001) groups vs. control and tended to lower NEFA (p = 0.08) in AT group vs. A group. Neither DECA, nor taurine influenced TC and LDL-C levels. Conclusions: Taurine partially prevented the occurrence of DECA negative effects on lipid profile, suggesting a therapeutic potential in several conditions associated with chronic high levels of plasma androgens, such as endocrine disorders or AAS-abuse.

Radiomic Profiling of Head and Neck Cancer: 18F-FDG PET Texture Analysis as Predictor of Patient Survival.

Background and Purpose: The accurate prediction of prognosis and pattern of failure is crucial for optimizing treatment strategies for patients with cancer, and early evidence suggests that image texture analysis has great potential in predicting outcome both in terms of local control and treatment toxicity. The aim of this study was to assess the value of pretreatment 18F-FDG PET texture analysis for the prediction of treatment failure in primary head and neck squamous cell carcinoma (HNSCC) treated with concurrent chemoradiation therapy. Methods: We performed a retrospective analysis of 90 patients diagnosed with primary HNSCC treated between January 2010 and June 2017 with concurrent chemo-radiotherapy. All patients underwent 18F-FDG PET/CT before treatment. 18F-FDG PET/CT texture features of the whole primary tumor were measured using an open-source texture analysis package. Least absolute shrinkage and selection operator (LASSO) was employed to select the features that are associated the most with clinical outcome, as progression-free survival and overall survival. We performed a univariate and multivariate analysis between all the relevant texture parameters and local failure, adjusting for age, sex, smoking, primary tumor site, and primary tumor stage. Harrell c-index was employed to score the predictive power of the multivariate cox regression models. Results: Twenty patients (22.2%) developed local failure, whereas the remaining 70 (77.8%) achieved durable local control. Multivariate analysis revealed that one feature, defined as low-intensity long-run emphasis (LILRE), was a significant predictor of outcome regardless of clinical variables (hazard ratio < 0.001, P=0.001).The multivariate model based on imaging biomarkers resulted superior in predicting local failure with a c-index of 0.76 against 0.65 of the model based on clinical variables alone. Conclusion: LILRE, evaluated on pretreatment 18F-FDG PET/CT, is associated with higher local failure in patients with HNSCC treated with chemoradiotherapy. Using texture analysis in addition to clinical variables may be useful in predicting local control.

Decreased paraoxonase 2 enzymatic activity in monocyte/macrophages cells. A comparative in vivo and in vitro study for diabetes.

AIM: To investigate peripheral blood monocytes/macrophages (Mo/Mᴓ) paraoxonase 2 (PON2) in diabetes and the factors modulating its activity. METHODS: One hundred and eighteen patients with newly diagnosed uncomplicated type 2 diabetes mellitus were compared regarding clinical, biochemical and oxidative stress parameters with 80 healthy subjects. The capacity of the peripheral blood mononuclear cells (PBMNC) to release pro-oxidants and to neutralise them was determined by measuring the respiratory burst (RB) and the intracellular antioxidant enzyme PON2. In vitro experiments were conducted on a differentiated monocytes cell line (dU937) that was exposed to serum deprivation followed by addition of isolated lipoproteins (VLDL or LDL). RESULTS: Paraoxonase 2 activity in Mo/Mᴓ was significantly lower in type 2 diabetes patients (0.042 ± 0.044 vs 0.165 ± 0.133U lactonase activity/mg protein in controls, p < .0005) and decreased in the obese in all groups. It was inversely correlated to parameters of adiposity (BMI and Waist Circumference), of glucose control (blood glucose, fructosamine and HbA1c) and insulin resistance (HOMA-IR). In multivariate regression models, 15-34% of the PON2 variance was explained by diabetes. The in vitro addition of VLDL normalised the RB of serum deprived dU937 cells, S- (to 82 ± 18% of the cells incubated with serum, S+) and PON2 activity (from 0.524 ± 0.061 in S - to 0.298 ± 0.048 U/mg protein). In contrast, when LDL was added, the RB remained lower (61 ± 12% of S+, p = .03) and PON2 higher (0.580 ± 0.030 U/mg protein, p = .003). CONCLUSIONS: The decrease in monocyte/macrophage PON2 enzymatic activity observed in type 2 diabetes cannot be totally explained by abdominal obesity and insulin resistance. The underlying molecular mechanisms need to be identified.

Impact of chronic administration of anabolic androgenic steroids and taurine on blood pressure in rats.

Supraphysiological administration of anabolic androgenic steroids has been linked to increased blood pressure. The widely distributed amino acid taurine seems to be an effective depressor agent in drug-induced hypertension. The purpose of this study was to assess the impact of chronic high dose administration of nandrolone decanoate (DECA) and taurine on blood pressure in rats and to verify the potentially involved mechanisms. The study was conducted in 4 groups of 8 adult male Wistar rats, aged 14 weeks, treated for 12 weeks with: DECA (A group); vehicle (C group); taurine (T group), or with both drugs (AT group). Systolic blood pressure (SBP) was measured at the beginning of the study (SBP1), 2 (SBP2) and 3 months (SBP3) later. Plasma angiotensin-converting enzyme (ACE) activity and plasma end products of nitric oxide metabolism (NOx) were also determined. SBP3 and SBP2 were significantly increased compared to SBP1 only in the A group (P<0.002 for both). SBP2, SBP3 and ACE activity showed a statistically significant increase in the A vs C (P<0.005), andvs AT groups (P<0.05), while NOx was significantly decreased in the A and AT groups vs controls (P=0.01). ACE activity was strongly correlated with SBP3 in the A group (r=0.71, P=0.04). These findings suggest that oral supplementation of taurine may prevent the increase in SBP induced by DECA, an effect potentially mediated by angiotensin-converting enzyme.

THE ROLE OF ESTROGENS AND ESTROGEN RECEPTORS IN MELANOMA DEVELOPMENT AND PROGRESSION.

Melanoma has a significant mortality and its growing incidence is associated with important social and health care costs. Thus, investigation of the complex mechanisms contributing to emergence and development of melanoma are of real interest both in scientific research and clinical practice. Estrogens play an important role in the emergence and development of certain types of cancer, such as breast cancer, endometrial cancer and ovarian cancer, but their role in development of cutaneous melanoma is still a matter of debate. Various data suggest that increased levels of endogenous estrogens during pregnancy or exposure to exogenous estrogens by use of oral contraceptives (OCs) and hormone replacement therapy (HRT) may have a potential role in melanoma development and progression. Moreover, there were revealed several intracellular pathways which can support the connection between estrogens, estrogen receptors (ER) and melanoma. While ER-ß plays an antiproliferative role, ER-α promotes cell growth and cellular atypia. Thus, inhibition of ER-ß activity in the skin can increase the risk for development of cutaneous melanoma and spread of metastatic cells. However, despite recent advances in this area, the exact role and clinical implications of estrogens and estrogen receptors in melanoma are still not entirely understood and require further investigations.

Impact of chronic administration of anabolic androgenic steroids and taurine on blood pressure in rats

Supraphysiological administration of anabolic androgenic steroids has been linked to increased blood pressure. The widely distributed amino acid taurine seems to be an effective depressor agent in drug-induced hypertension. The purpose of this study was to assess the impact of chronic high dose administration of nandrolone decanoate (DECA) and taurine on blood pressure in rats and to verify the potentially involved mechanisms. The study was conducted in 4 groups of 8 adult male Wistar rats, aged 14 weeks, treated for 12 weeks with: DECA (A group); vehicle (C group); taurine (T group), or with both drugs (AT group). Systolic blood pressure (SBP) was measured at the beginning of the study (SBP1), 2 (SBP2) and 3 months (SBP3) later. Plasma angiotensin-converting enzyme (ACE) activity and plasma end products of nitric oxide metabolism (NOx) were also determined. SBP3 and SBP2 were significantly increased compared to SBP1 only in the A group (P<0.002 for both). SBP2, SBP3 and ACE activity showed a statistically significant increase in the A vs C (P<0.005), andvs AT groups (P<0.05), while NOx was significantly decreased in the A and AT groups vs controls (P=0.01). ACE activity was strongly correlated with SBP3 in the A group (r=0.71, P=0.04). These findings suggest that oral supplementation of taurine may prevent the increase in SBP induced by DECA, an effect potentially mediated by angiotensin-converting enzyme.

Combinatorial approach for improving the outcome of angiogenic therapy in ischemic tissues.

Two major populations of endothelial progenitor cells (EPC), namely endothelial colony forming cells (ECFC, or late outgrowth EPC) and circulating angiogenic cells (CAC, or early outgrowth EPC) have been reported to play important roles in vasculogenesis in numerous pathological conditions. However, the poor retention of cells into the ischemic tissue and neovessel fragility are two major flaws that need to be overcome for successful angiogenic therapy. The objective of this study was to explore and exploit the functional properties of EPC populations in order to increase the effectiveness of post-ischemic cell therapy. The results indicate different, still complementary, effects of the two EPC populations on adherence and proliferation of vascular endothelial cells. Matrigel plug assay and mouse hind limb ischemia model showed that concomitant administration of CAC-secreted factors and ECFC resulted in three-fold increase in local cell retention and improved muscle perfusion, vessel maturation and hind limb regeneration, in comparison to either treatment alone. By concluding, factors secreted by CAC co-administered at the time of ECFC transplantation improve tissue regeneration and vascular repair through stabilization of newly-derived blood vessels.

Impact of maternal melatonin suppression on forced swim and tail suspension behavioral despair tests in adult offspring.

Melatonin is an essential hormone, which regulates circadian rhythms and has antioxidative and anticarcinogenic effects. As melatonin secretion is suppressed by light, this effect was examined on the offspring of the Wistar rat females exposed to continuous light (500 lux) during the second half of the pregnancy (day 12 to 21). Control rats were kept under a 12:12 light-dark cycle. The resulted male offspring have been behaviorally assessed for depression after postnatal day 60 by using Forced Swim Test (FST) and Tail Suspension Test (TST). Animals resulted from the melatonin deprived pregnancies have developed an abnormal response in the TST, but a normal FST behavior. Also, TST active movement was different in the melatonin suppression group compared to the control group. These findings suggest that intrauterine melatonin deprivation might be linked to the depressive like behavior in adult male offspring.

Fronto-parietal connectivity changes following noxious stimulation during anesthesia.

RATIONALE: The aim of our study was to assess the changes in the fronto-parietal connectivity estimated by the cross approximate entropy (XAppEn) during noxious stimulation while under chloral hydrate anaesthesia, in rats. METHOD: A group of 11 Wistar rats chronically implanted with Ni-Cr electrodes, which were placed on the dura mater of the right hemisphere (over the olfactory cortex, the frontal and the parietal lobes), were used in the present study. Noxious stimuli of a mechanical and thermal nature were applied on the left hindpaw during chloral hydrate anesthesia. The anesthetic depth was estimated through median frequency computation, which in that instance was of 2-3 Hz. Fronto-parietal functional cortical connectivity was assessed by using XAppEn. RESULTS: After data processing and analysis we observed an increase of fronto-parietal functional connectivity during mechanical and thermal noxious stimulation. In addition, MEF increased both in frontal and parietal areas during the mechanical and thermal stimulation compared to baseline. CONCLUSION: Mechanical and thermal stimulation induces an increase in the fronto-parietal connectivity during chloral hydrate anesthesia in rats.

[Axillary lymph node metastases in breast cancer. Anatomo-clinical correlation and surgical approach]. / Metastazele ganglionare limfatice axilare în cancerul mamar. Corelatii anatomo-clinice si atitudine chirurgicala.

AIM: To establish the incidence of the axillary lymph node metastasis in breast cancer and some anatomo-clinical correlations useful for surgical act orientation. MATERIAL AND METHOD: The data from 450 patients, who underwent surgery for breast cancer between 2000 and 2007, were analyzed statistically according to some parameters: the age of the patients, the size and the location of the tumor, the hystopathological type, the elapsed time from the discovery of the tumor until surgery. RESULTS: The tumoral stage was: stage 0--1.1%, I--7.11%, II--50.67%, III--33.78%, IV--7.33%. From the total amount of patients who underwent surgery, only 56.44% had axillary lymph node metastasis. The patients in the forth decade of life had more frequently axillary lymph node involvement, and also those from rural habitat (65.88%). The correlation between tumor dimension and lymph node involvement was: <2 cm--1.36%, 2-5 cm--48.71%, >5 cm--86.67%. The palpation of the armpit was associated in almost a quarter of cases with false negative or false positive diagnosis. There are a lot of locally advanced cases without axillary lymph node metastases. CONCLUSIONS: Axillary lymph node status is strongly correlated with the tumor dimension and the elapsed time between diagnosis and treatment. The numerous cases of axillary lymphadenectomy without lymph node metastases (43.55%), even in locally advanced cases, advocate for a wider application of lymphatic mapping and sentinel lymph node biopsy, to avoid the pathology associated with those axillary dissections.

[Intestinal tuberculosis in children. Differential diagnosis and treatment]. / Tuberculoza intestinala la copil. Diagnostic diferential, conduita terapeutica.

Lately, tuberculosis has became a top priority problem in health all over the world. The actual level of epidemiological indicates of tuberculosis Shaw that Romania is the country that has the most unfavorable situation in Europe except for Bosnia-Herzegovina. Tuberculosis incidence from 1996 to 1997 ranks Dolj county second in Romania from the point of view of the increasing rate (154.3% + 25.4% versus 107% + 4.3%). The National Programme of Controlling Tuberculosis for 1997-2000 has as main object the neutralization of a least 85% of the discovered contamination sources. At the same time with the pulmonary tuberculosis were discovered 17.2% extrapulmonary localizations. The purpose of these works is that of presenting in the frame of extrapulmonary TBC the localization of intestinal TBC with children (peritonitic form with infants and pseudotumoral with child). In class cooperation with the veterinary Medicine Service we have also studied the possibility of same sources of TBC infection of animal origin, knowing the fact that besides the human Koch bacillus were discovered bovine, ovine, poultry sources. Presenting a number of 16 cases of intestinal tuberculosis with children, rare cases of extra pulmonary tuberculosis, the authors also present 2 cases with children whose differential diagnosis had to be made ou a histopathological base between tuberculosis with an abdominal lymphoma or peritonitic carcinomatosis. The results of the surgical treatment that made the diagnosis with the help of the histopathological examination and the tuberculostatic treatment were very good, the evolution and the control in true of all the patients, proving that intestinal tuberculosis extrapulmonary form with children can be cured.

Treatment with zincum metallicum CH5 in patients with liver cirrhosis. Preliminary study.

The zinc, an important enzymatic cofactor, is involved in many metabolic processes. Its deficiency might be due either to malabsorption or to excessive utilization. In the medical literature of the latest 10 years, zinc was considered to play a part in the immune processes. The authors of the present paper intend to study the zinc and immunoglobulin levels in various diseases, i.e., chronic progressive hepatitis, liver cirrhosis (LC), dermatitis, bronchial asthma. This preliminary investigation was carried out in 30 patients with LC in whom serum zinc values were assayed by atomic absorption spectrophotometry and the immunoglobulin levels were determined using the Mancini type simple radial immunodiffusion technique. All these patients presented considerable decrease of serum zinc concentration, the values ranging between 3.06 and 7.65 mumol/l as compared with 19.8 +/- 1.5 mumol/l in the controls, alongside with the increase of immunoglobulins G and M. In the patients treated with Zincum metallicum CH5 it was observed after about 30 days of treatment that the clinical state was considerably improved and IgG and IgM as well as serum zinc had resumed their normal values. This treatment should not be interrupted since in LC, without permanent additional supply, the serum zinc returns rapidly to the initial deficit or even lower.

The IgD-zinc relationship in patients with allergic bronchial asthma.

In recent years, evidence was brought of the zinc ion (Zn++) interference in the mechanism of certain processes occurring at molecular level, i.e., the protein synthesis, the activity of some enzymatic complexes, the regulation of transmembranal transport or the processes of immune regulation. The present paper investigates the variations of the immunoglobulin classes in patients with bronchial asthma, particularly the relationship between IgD levels and those of the zinc ion in the blood serum.

[Therapeutic considerations on a case of post-transfusion intravascular hemolysis]. / Consideratii terapeutice pe marginea unui caz de hemoliza intravasculara posttransfuzionala

A case is presented of intravascular hemolysis following incompatible transfusion of 500 ml hetero-group blood in a patient aged 29 years that had undergone emergency surgery for intra-abdominal hemorrhagic syndrome. Stress is laid on volemic therapy, on osmotic treatment and on the administration of alkalines in the first hours following the accident.