Lack of BCL-2 confers interferon-alpha sensitivity to B-cell lymphomas

Hairy cell leukemia (HCL) is a chronic B-cell lymphoproliferative disorder with pathological manifestations usually including splenomegaly and panctopenia. Interferons (IFNs), specifically of the α subtypes have shown a significant anti-tumor effect in HCL patients, with improvement of hematological parameters within the first few months of treatment. However, the therapeutic effect of IFN-α is still rather limited. The mechanisms responsible for the beneficial action of IFN-α in HCL patients are unclear. A continuous line of cells (Eskol) from a patient diagnosed with HCL was established and shown to have several properties of HCL. Even though, Eskol cells are very resistant to anti-proliferative activity of IFN-α, Daudi cells, another human B-cell-derived cell line, are very sensitive to anti-proliferative activity of IFN-α and are commonly used as a model cell to test anti-proliferative effect of IFN-α. To understand the molecular reason(s) behind the observed obvious differences to IFN sensitivity of above cells, we have analyzed the expression levels of BCL2, caspase-1, Laminin and PARP in these cells. We found that Daudi cells do not express BCL2 at all, and probably because of that, these cells have constantly cleaved, and probably activated form of caspase-1. However, when we overexpresed BCL2 in these cells, they lost processed form of caspase-1 and became resistant to anti-proliferative activity of IFN-α. These results let us to suggest that IFN-α sensitivity of B-cell lymphomas, once again, depends on the presence or absence of BCL2.     

Universal Markers of Thyroid Malignancies: Galectin-3, HBME-1, and Cytokeratin-19

Difficulties in diagnosis of thyroid lesions, even with histologic analysis, are well known. This study has been carried on to evaluate the role of immunohistochemical markers including galectin-3, Hector Battifora mesothelial cell-1 (HBME-1), and cytokeratin-19 in the diagnosis and differential diagnosis of benign and malignant thyroid lesions. The expressions of galectin-3, HBME-1, and cytokeratin-19 were tested in formalin-fixed, paraffin-embedded tissues from 458 surgically resected thyroid lesions including non-neoplastic and neoplastic lesions. Immunostaining with standard avidin–biotin complex technique was performed by using monoclonal antibodies. In malignant neoplastic thyroid lesions, galectin-3, HBME-1, and cytokeratin-19 were diffusely expressed in general. Diffuse expression rates of these three markers were 72.3% (47/65), 70.7% (46/65), and 76.9% (50/65), respectively. The use of galectin-3, HBME-1, and cytokeratin-19 may provide significant contributions in the differential diagnosis of malignant thyroid tumors. Although focal galectin-3, HBME-1, and cytokeratin-19 expression may be encountered in benign lesions, diffuse positive reactions for these three markers are characteristic of malignant lesions. It has concluded that cytokeratin-19 alone and its combinations with other markers were more sensitive in accurate diagnosis of papillary carcinoma than the other combinations; meanwhile, there were similar results for follicular carcinomas with HBME-1 alone and its combinations.     

Bahcesehir long-term population-based screening compared to National Breast Cancer Registry Data: effectiveness of screening in an emerging country

PURPOSEWe aimed to show the effects of long-term screening on clinical, pathologic, and survival outcomes in patients with screen-detected breast cancer and compare these findings with breast cancer patients registered in the National Breast Cancer Registry Data (NBCRD).METHODSWomen aged 40–69 years, living in Bahcesehir county, Istanbul, Turkey, were screened every 2 years using bilateral mammography. The Bahcesehir National Breast Cancer Registry Data (BMSP) data were collected during a 10-year screening period (five rounds of screening). BMSP data were compared with the NBCRD regarding age, cancer stage, types of surgery, tumor size, lymph node status, molecular subtypes, and survival rates.RESULTSDuring the 10-year screening period, 8758 women were screened with 22621 mammograms. Breast cancer was detected in 130 patients; 51 (39.2%) were aged 40–49 years. The comparison of breast cancer patients in the two programs revealed that BMSP patients had earlier stages, higher breast-conserving surgery rates, smaller tumor size, more frequent negative axillary nodal status, lower histologic grade, and higher ductal carcinoma in situ rates than NBCRD patients (p = 0.001, for all).CONCLUSIONThese results indicate the feasibility of successful population-based screening in middle-income countries.

Breast cancer is the most frequent cancer and cause of cancer-related deaths among Turkish women, as well as globally (1–5). Although the incidence of breast cancer increases every year, mortality rates are decreasing in developed countries because of nationwide screening programs and modern treatment options (5, 6). An invited mammography screening program for women aged between 40 and 69 years revealed a 60% reduction in cancer-related 10-year mortality in a landmark study (7). A systematic review of Myers et al. (8) showed that breast cancer screening reduced mortality by 20% in average-risk women of all age groups. However, this review did not evaluate the differences between annual and biannual mammographic screening.In 2004, the Cancer Control Department of Turkey recommended biannual mammographic screening for women aged 50–69 years, based on European Guidelines. The population of Turkey is relatively young, and almost half of all breast cancer patients in Turkey are younger than 50 years. According to and National Breast Cancer Registry Data (NBCRD) reports, the starting age for mammography screening was set as 40 years. The Bahcesehir Mammographic Screening Program (BMSP) was the first organized population-based 10-year (2009–2019) mammography screening program in Turkey, a middle-income country.Turkish Federation of Breast Diseases Societies started a voluntary data registry program that was provided by breast surgeons working in secondary or tertiary hospitals. This program aimed to collect detailed information of breast cancer patients and to pool comprehensive country-specific breast cancer data. This registry, namely the NBCRD, was the first specified database on breast cancer in the country and was started in 2005, before the BMSP (9). Data from 36 centers were collected for 10 years. However, the cancer registry is a standard database containing general information as defined by the International Agency for Research on Cancer standards.The aim of this study was to show the feasibility of a population-based breast cancer screening program in an emerging, middle-income country, Turkey. The objective of our study was to evaluate the effectiveness of a population-based breast cancer screening program by comparing it with NBCRD data.     

Dose-dependent neuroprotective effect of enoxaparin on cold-induced traumatic brain injury

Recent evidence exists that enoxaparin can reduce brain injury because of its anticoagulant activity. To investigate the potential therapeutic effect of enoxaparin on cold-induced traumatic brain injury, at 20 minutes after modeling, male BALB/c mouse models of cold-induced traumatic brain injury were intra-peritoneally administered 3 and 10 mg/kg enoxaparin or isotonic saline solution. Twenty-four hours later, enoxaparin at 10 mg/kg greatly reduced infarct volume, decreased cell apoptosis in the cortex and obviously increased serum level of total antioxidant status. By contrast, administration of enoxaparin at 3 mg/kg did not lead to these changes.These findings suggest that enoxaparin exhibits neuroprotective effect on cold-in-duced traumatic brain injury in a dose-dependent manner.     

Obesity: a possible risk factor for restless legs syndrome

Aim/Background: Restless legs syndrome (RLS) is a frequent neurological and sleep disorder. Metabolic disorders are known to be related to sleep disorders. We prospectively evaluated whether obesity and its possible cofactors were related to the presence of RLS.

Materials and Methods: The study included 143 obese and 94 non-obese individuals. Obese patients had a BMI of 30 and over, while non-obese patients had a BMI lower than 30. Patients with arthritis and pregnancy were excluded but not those with diabetes mellitus. Participants who met diagnostic criteria recommended by the International RLS Study Group were diagnosed as having RLS. Depression, anxiety, daytime sleepiness, insomnia and sleep quality were evaluated in detail.

Results: The mean age of obese patients was 40.52 years and that of non-obese patients was 39.76 years. The mean body mass index was 36.77 in the obese group and 25.71 in the non-obese group. The occurrence of depression, anxiety, sleep quality, and insomnia scores were significantly higher in obese individuals. The evaluations of daytime sleepiness, sleep efficiency and sleep latency were not significantly different between the groups.

Discussion: Although the presence of RLS was correlated with obesity and vascular risk factors at a significant level, it was also shown that depression, anxiety and insomnia were significantly frequent in obese patients (although not daytime sleepiness). Further studies are needed.     

Emergency thyroidectomy: Due to acute respiratory failure

INTRODUCTION

Giant cervical and mediastinal goiter may lead to acute respiratory failure caused by laryngotracheal compression and airway obstruction. Here, we present a case admitted to the emergency service with a giant goiter along with respiratory failure and poor general health status, which required urgent surgical intervention.

PRESENTATION OF CASE

A 71-year-old female admitted to the emergency room with shortness of breath and poor general health status resulting from a giant cervical swelling progressively increased during the last 7 years and constituted severe respiratory failure which has become severe in the last one month. A giant nodular goiter of the left thyroid lobe extending retrosternally, causing tracheal compression, limiting the neck movements was detected with clinical examination and bedside ultrasound. Emergency thyroidectomy was planned. Fiberoptic-assisted awake nasal intubation was performed in the operating room. Emergency total thyroidectomy was performed for the life-threatening respiratory failure. Postoperative period was uneventful. She was transferred from intensive care unit to the ward on postoperative day 3 and was discharged from the hospital on the postoperative 7th day. Benign multinodular hyperplasia was reported on the histopathological report. Patient was included in routine follow-up.

DISCUSSION

In the present case tracheal destruction due to compression of the giant goiter was found in agreement with previous reports. Emergency thyroidectomy was performed after awake intubation since it is a common surgical option for the treatment of giant goiter causing severe airway obstruction.

CONCLUSION

Respiratory failure due to giant nodular goiter is a life-threatening situation and should be treated immediately by performing awake endotracheal intubation following emergency total thyroidectomy.     

Is oxidative stress related to childhood urolithiasis?

Background

Urolithiasis is a common condition in pediatric populations in Turkey. The role of oxidative stress in renal stone formation in pediatric patients has not been reported to date. The aim of this study was to assess oxidative stress in childhood urolithiasis.

Methods

Seventy-four children diagnosed with urolithiasis and 72 healthy control subjects were enrolled in the study. Kidney stone formers were evaluated by analysis of metabolic conditions related to urolithiasis, such as hypercalciuria, hyperoxaluria, hypocitraturia and hyperuricosuria. Urine total antioxidant status (TAS), and total oxidant status (TOS) were measured, and oxidative stress index (OSI) was calculated as an indicator of the degree of oxidative stress.

Results

Among the stone formers, metabolic analyses revealed that 30 % had hypercalciuria, 45 % had hypocitraturia, 6 % had hyperoxaluria and 40 % had hyperuricosuria. Elevated levels of the renal tubular damage marker urinary N-acetyl- beta-d-glucosaminidase (NAG) was elevated in 25 % of the patient group, but microalbuminuria was not detected. Total oxidant status and total antioxidant status were significantly higher in stone formers than in the controls (p?=?0.023 and 0.004, respectively). In addition, urinary NAG was significantly correlated with TOS (r?=?0.427, p?=?0.019).

Conclusions

The results of this study show that oxidative stress may play an important role in the pathogenesis of pediatric stone formers.     

Connexin 32 mutation in a Turkish family with X-linked Charcot-Marie-Tooth disease

In the present work, we describe a large Turkish family (N=39) with Charcot-Marie-Tooth disease, which is the most commonly inherited peripheral neuropathy. The subjects were from four generations, including six hemizygote patients and nine heterozygote carrier females. Symptoms appeared in late childhood in males (mean age=13.5) but later in carrier females (mean age=33.5). The peripheral nerve conduction was more severely affected in males than females. Genomic DNA was isolated from peripheral white blood cells. Using SSCP technique (single strand conformation polymorphism analysis), abnormal patterns of migration were observed in 15 subjects: 6 of them were hemizygote males and 9 were heterozygote carrier females. We identified a mutation of the Cx32 gene, consisting of a guanine to adenine transition at position 271 (271G-A). The results suggested relations between degenerative processes and position of Cx32 mutations.     

Effects of exercise on gallbladder volume and motility in obese women

PURPOSE: Comparatively few prospective studies have investigated the relationship between physical activity and gallbladder motility, and the results are controversial. Exercise may affect gallbladder motility via neural or hormonal mechanisms. The purpose of this study was to evaluate the possible effects of aerobic exercise on gallbladder motility in a group of obese women without gallstones. PATIENTS AND METHODS: Twenty-three obese women (age 41.2+/-10.3 years, body mass index 40.7+/-6.7 kg/m(2)) were included in the study. Following an overnight fast, fasting and postprandial (15, 30, 45, 60, 75, 90, 120, and 150 minute) volumes and ejection fractions were evaluated with real-time ultrasonography before exercise. For all subjects, the exercise regimen consisted of daily 45-minute walking sessions at 60-80% of maximum heart rate for 4 weeks except weekends. Gallbladder volume and ejection fraction were again evaluated after exercise. RESULTS: Fasting and postprandial (15, 30, 45, 60, 75, 90, 120, and 150 minute) volumes were 38.6+/- 10.9, 32.8+/- 8.8, 27.6/- 8.1, 22.7+/- 8.5, 21.4+/- 7.2, 20.8+/- 7.0, 22.8+/- 7.3, 29.6 +/- 7.0, and 36.8+/- 6.2 cm(3) before the exercise period, respectively, and 40.8+/- 18.9, 29.9+/-11.2, 25.3+/- 9.2, 22.4+/-8.5, 19.6+/-7.8, 17.7+/- 6.8, 17.8+/- 7.3, 23.1+/-10.8, and 29.0+/-14.4 cm(3) after the exercise period, respectively. Postprandial (15, 30, 45, 60, 75, 90, 120, and 150 minute) ejection fractions were 13.5+/-15.9, 27.4+/-15.4, 39.5+/-20.0, 43.2+/-16.7, 44.3+/-17.3, 37.5 +/- 23.5, 23.5 +/-25.1, and 5.5+/- 21.6% before the exercise period, respectively, and 22.6+/- 20.1, 34.6+/-14.5, 42.0+/-13.6, 49.2+/-12.6, 53.1+/-14.1, 52.6+/-16.1, 43.6+/-17.0, and 29.2+/- 26.5% after exercise, respectively. After the exercise period, the 75, 90, 120, and 150 minute volumes were lower (p< 0.05, p< 0.05, p< 0.05, p< 0.01) and the 90, 120, and 150 minute ejection fractions were higher than before exercise (p< 0.05, p < 0.05, p< 0.01). CONCLUSIONS: Our study showed that exercise decreased late-phase postprandial gallbladder volume and increased late-phase postprandial gallbladder motility in these obese women.