In vitro antimicrobial susceptibility of Brucella species

MIC50 and MIC90 values of doxycycline, rifampicin, ciprofloxacin, trimethoprim-sulphamethoxazole and ceftriaxone for 42 blood isolates of Brucella species were determined using the Etest. Thirty-seven isolates were identified as B. melitensis and five as B. abortus. Doxycycline had the lowest and rifampicin the highest MIC50 values. Four strains were non-susceptible to rifampicin, and one strain was resistant to trimethoprim-sulphamethoxazole. There is no significantly important resistance problem for antibiotics targeted against Brucella species in Turkey. However, since rifampicin is commonly used for prevalent diseases such as tuberculosis, the regional susceptibility pattern of rifampicin should be assessed periodically.     

Bone marrow microvessel density (MVD) in adult acute myeloid leukemia (AML): therapy induced changes and effects on survival

Based on the strong evidence in favor of an increase in microvessel density (MVD) in hematological malignancies, we evaluated VEGF immunoreactivity and MVD measurement in bone marrow biopsies of 36 AML patients at diagnosis and following therapy. MVD assessment was based on CD31, CD34 expressing vessels. The values were calculated for only one marker if the other vascular marker was positive on blasts, otherwise both markers were used. VEGF immunoreactivity was also scored. Comparison of MVD values of 36 AML patients with 18 non-malignant controls showed a significantly higher MVD in AML (CD31: P = 0.004, CD34: P < 0.001), which is independent of other variables such as cellularity or blast percentage. Following induction chemotherapy, the responders showed a significant decrease in blast counts (P < 0.001), cellularity (P = 0.001) and MVD (P = 0.050) quantification with CD31. Higher baseline MVD (CD34) values were associated with shorter overall survival (P = 0.0027). These results are encouraging for inclusion of MVD enumeration in bone marrow examinations of AML patients at diagnosis as an additional prognostic factor.     

Cefepime-induced non-convulsive status epilepticus in a peritoneal dialysis patient

Non-convulsive status epilepticus related to cefepime has not been reported in childhood dialysis patients, although several adult cases have been reported. We report a state of acute confusion in a 15-year-old boy on continuous ambulatory peritoneal dialysis (CAPD) receiving cefepime that was diagnosed as status epilepticus by electroencephalography (EEG). The EEG improved after anticonvulsive therapy. All clinical symptoms disappeared dramatically within 24 h of discontinuation of cefepime. The differential diagnosis of confusional states and the mechanisms of the convulsive effects of antimicrobials in chronic renal failure are discussed. The importance that the clinician is aware of the rare side effects of antimicrobials is emphasized.     

Physiopathology hypotheses and treatment of pulmonary sequestration

Illustrated by this case report, partial obstruction of the venous collector of extrapulmonary sequestration explains pleural effusion and fetal hydrops. Therapy requires fetal thoracentesis and neonatal arterial occlusion of the pedicle artery allowing uneventful follow-up.     

Effects of onabotulinumtoxinA treatment on efficacy,depression, anxiety,and disability in Turkish patients with chronic migraine

Chronic migraine causes a serious labour loss and disability in the society and increases the risk of depression and anxiety by negatively affecting the quality of life. The purpose of this study was to investigate the effects of onabotulinumtoxinA (BoNT-A) treatment on efficacy before and after treatment in our cases with chronic migraine as well as on depression, anxiety and disability caused by migraine. According to the International Headache Classification (ICHD-III beta version), 60 adult patients who were diagnosed with chronic migraine were included in the study. A total of 155 IU BoNT-A treatment from 31 regions was administered in accordance with the protocol of PREEMPT study. Information about the characteristics of patients’ headaches, background and family history, drugs they used was recorded. At the baseline and in the first and third month after the BoNT-A injection, VAS scores, the number of both headache days and attacks, the headache duration, the frequency of application to emergency services and the intake of both analgesics and triptans during attacks were evaluated. MIDAS, BDI and BAI were evaluated at the baseline and in the third month after the BoNT-A injection. BoNT-A injection provided a significant decrease in the number of days and severity of headaches, MIDAS disability scores and psychiatric complaints in cases with chronic migraine who did not respond to prophylactic treatments in the third month of the treatment.     

Negative and interactive effects of sex,aging, and alcohol abuse on gray matter morphometry

Chronic alcohol use is associated with declines in gray matter (GM) volume, as is the normal aging process. Less apparent, however, is how the interaction between aging and heavy alcohol use affects changes in GM across the lifespan. There is some evidence that women are more vulnerable to the negative effects of alcohol use on GM than men. In the current study, we examined whether localized GM was related to measures of alcohol use disorder (e.g., AUDIT score) in a large sample (N = 436) of participants, ages 18–55 years, with a range of disease severity, using both voxel‐based morphometry (VBM) and surface‐based morphometry (SBM). We also explored whether GM associations with alcohol use disorder (AUD) severity are moderated by sex and age. Results showed significant negative associations between AUD severity and GM volume throughout temporal, parietal, frontal, and occipital lobes. Women showed more negative effects of alcohol use than men for cortical thickness in left orbitofrontal cortex, but evidence for increased vulnerability based on sex was limited overall. Similarly, a specific age by alcohol use interaction was observed for volume of right insula, but other regional or global interactions were not statistically supported. However, significant negative associations between heavy alcohol use and GM volumes were observed as early as 18–25 years. These findings support that alcohol has deleterious effects on global and regional GM above and beyond age, and, of particular importance, that regional associations emerge in early adulthood. Hum Brain Mapp 37:2276–2292, 2016. © 2016 Wiley Periodicals, Inc.     

Two novel GALNT3 mutations in familial tumoral calcinosis

Familial tumoral calcinosis (TC) is characterized by elevated serum phosphate concentrations, normal or elevated 1,25(OH)2 vitamin D, as well as periarticular and vascular calcifications. Recessive mutations in the mucin-like glycosyltransferase GalNAc transferase-3 (GALNT3) and the phosphaturic hormone fibroblast growth factor-23 (FGF23) have been shown to result in TC. In the present study, mutational analyses were performed on two patients with TC to determine the molecular basis of their diseases. Analysis of the first patient revealed a novel, homozygous base insertion (1102_1103insT) in GALNT3 exon 5 that results in a frameshift and premature stop codon (E375X). The second patient had a novel homozygous transition (1460 g>a) in GALNT3 exon 7, which caused a nonsense mutation (W487X). Both mutations are predicted to markedly truncate the mature GALNT3 protein product. Although the patients carry GALNT3 mutations, these individuals presented with low-normal serum concentrations of intact biologically active FGF23 and high levels of C-terminal FGF23. In order to discern a possible relationship between GALNT3 and FGF23 in TC, a comprehensive assessment of the reported TC mutations was also performed. In summary, we have detected novel GALNT3 mutations that result in familial TC, and show that disturbed serum FGF23 concentrations are present in our TC cases as well as in previously reported cases. These studies expand our current genetic understanding of familial TC, and support a pathophysiological association between GALNT3 and FGF23.     

Is lipid lowering treatment aiming for very low LDL levels safe in terms of the synthesis of steroid hormones?

Today atherosclerotic diseases are among the most important causes of death in the world. Epidemiological, clinical, genetic, experimental and pathological studies have clearly shown the role of lipoproteins in atherosclerosis. LDL is the major atherogenic lipoprotein and has been defined as the primary target of lipid lowering treatment by NCEP. Although the level of LDL, the primary target in the treatment of dyslipidemia, has been set as below 100 mg/dl in coronary heart diseases (CHD) and CHD risk equivalents, this level has been pulled down to below 70 mg/dl for the group defined as very high risk group by the ATP (Adult Treatment Panel) guide that has been updated following the new clinical studies. As we already know, cholesterol is the precursor of glucocorticoids, mineralocorticoids and sex steroids, besides being a structural component of the cell membrane. Both adrenal and non-adrenal (ovarian+testicular) all steroid hormones are primarily synthesized using the LDL-cholesterol in the circulation. In addition to this, there is 'de novo' cholesterol synthesis in both the adrenals and gonads controlled by the HMG-CoA reductase enzyme. A third pathway, which under normal circumstances has little contribution as compared to the first two, is the use of circulatory HDL-cholesterol by the adrenal and gonadal tissues for the synthesis of steroids. Our knowledge on extremely lowered LDL levels is quite limited. However, since statins both decrease circulatory LDL and inhibit de novo cholesterol synthesis, they are likely to affect the synthesis of steroid hormones.     

Enhancement of docetaxel-induced cytotoxicity and apoptosis by all-trans retinoic acid (ATRA) through downregulation of survivin (BIRC5), MCL-1 and LTbeta-R in hormone- and drug resistant prostate cancer cell line,DU-145

Background

The management of hormone-refractory prostate cancer (HRPC) still remains as an important challenge of daily oncology practice. Docetaxel has proved to be a first line treatment choice. All-trans retinoic acid (ATRA) could potently inhibit the growth of prostate cancer cells in vitro and its combination with various anticancer agents results in increased cytotoxicity. Based on these data, our aim was to examine the synergistic/additive cytotoxic and apoptotic effects of combination of docetaxel and ATRA, in hormone- and drug refractory human DU-145 prostate cancer cells. Furthermore, we have searched for the underlying mechanisms of apoptosis by demonstrating apoptosis-related genes.

Methods

XTT cell proliferation assay was used for showing cytotoxicity. For verifying apoptosis, both DNA Fragmentation by ELISA assay and caspase 3/7 activity measurement were used. For detecting the mechanism of apoptosis induced by docetaxel-ATRA combination, OligoGeArray^® which consists of 112 apoptosis related genes was used.

Results

Our results revealed that docetaxel and ATRA were synergistically cytotoxic and apoptotic in DU-145 cells, in a dose- and time dependent manner. It was also shown by our studies that apoptosis was induced in DU-145 prostate carcinoma cells with significant cytotoxicity, no matter which agent applied first. We have found out that docetaxel-ATRA combination significantly downregulates survivin (BIRC5), myeloid cell leukemia-1 (MCL-1) and lymphotoxin β-receptor (LTβR) genes, which all three have pivotal roles in regulation of apoptosis and cell cycle progression.

Conclusion

In conclusion, we strongly suggest that docetaxel and ATRA combination is a good candidate for this challenging era of daily oncologic practice. Also, the combination of docetaxel and ATRA might allow a reduction in docetaxel doses and by this way may diminish docetaxel adverse effects while maintaining the therapeutic effect in patients with HRPC.     

The advantage of total thyroidectomy to avoid reoperation for incidental thyroid cancer in multinodular goiter

HYPOTHESIS: To investigate the impact of total thyroidectomy on the rate of completion thyroidectomy for incidentally found thyroid cancer in euthyroid multinodular goiter. DESIGN: A randomized, prospective clinical trial. SETTING: A tertiary referral center. PATIENTS: Patients with euthyroid multinodular goiter without any preoperative suspicion of malignancy, history of familial thyroid cancer, or previous exposure to radiation were randomized (according to a random table) to total or near-total thyroidectomy leaving no remnant tissue or less than 1 g (group 1; n = 109) or bilateral subtotal thyroidectomy leaving 5 g or more of remnant tissue (group 2; n = 109). Patients with preoperative or perioperative suspicion of malignancy were excluded. MAIN OUTCOME MEASURES: We compared the complication rates and the incidence of thyroid cancer requiring radioactive iodine ablation and completion thyroidectomy between groups. RESULTS: There were no permanent complications. The rates of temporary unilateral vocal cord dysfunction and hypoparathyroidism showed no significant difference between groups 1 and 2 (0.9% vs 0.9% and 1.8% vs 0.9%, respectively; P>.05). Papillary cancer was found in 10 group 1 patients (9.2%) and 8 group 2 patients (7.3%) (P =.80). Of the 9 patients requiring radioactive iodine ablation, reoperation was avoided in 5 group 1 patients; the remaining 4 group 2 patients underwent completion thyroidectomy (P =.007). CONCLUSION: We recommend total or near-total thyroidectomy in multinodular goiter to eliminate the necessity for early completion thyroidectomy in case of a final diagnosis of thyroid cancer.