Production of Soluble Receptor Activator of Nuclear Factor Kappa-Β Ligand and Osteoprotegerin by Apical Periodontitis Cells in Culture and Their Modulation by Cytokines.

RANKL, a bone-destructive cytokine, and OPG, its osteoprotective counterpart, are expressed in periapical lesions (PLs), which represent hystopatological manifestations of apical periodontitis. However, their regulation in PLs has not been elucidated yet. Therefore, our aim was to study the production of RANKL and OPG and their modulation by pro- and anti-inflammatory cytokines in PL cell cultures. Isolated PL cells were cultured alone or with addition of TNF-α, IFN-ϒ, IL-17, IL-4, IL-10, and IL- 33, respectively. The levels of RANKL and OPG in supernatants were measured by ELISA. The proportion of CD3+ (T cells) and CD19+/CD138+ (B cells/plasma cells) within isolated PLs was determined by immunocytochemistry. The levels of RANKL were higher in cultures of symptomatic PLs compared to asymptomatic PLs and PLs with the dominance of T cells (T-type lesions) over B cells/plasma cells (B-type lesions). A higher proportion of osteodestructive processes (RANKL/OPG ratio > 1.0) were detected in symptomatic PLs. The production of RANKL was upregulated by IFN-ϒ and IL-17 and higher concentrations of IL-33. IL-10 and lower concentrations of IL-33 augmented the production of OPG. The addition of either RANKL or anti-RANKL antibody to the cultures did not modify significantly the production of OPG. In conclusion, this original PL cell culture model suggests that increased bone destruction through upregulated production of RANKL could be associated with exacerbation of inflammation in PLs with the predominance of Th1 and Th17 responses and increased secretion of IL-33. In contrast, IL-10 and lower levels of IL-33, through upregulation of OPG, may suppress osteolytic processes.

Validity of ultrasound-guided aspiration needle biopsy in the diagnosis of micrometastases in sentinel lymph nodes in patients with cutaneous melanoma.

Background/Aim: Cutaneous melanoma is one of the most aggressive solid cancers, that develops local, regional and distant metastases. The presence of metastases in lymph nodes is in correlation with Breslow tumor thickness. According to various researches, in melanoma with more than 4 mm Breslow thickness, lymph node micrometastases can be found in 60-70% of cases. Sentinel lymph nodes biopsy is a diagnostic procedure for lymph node micrometastasis detection, which is necessary for disease staging. In recent studies, ultrasound-guided fine needle aspiration with cytology (US FNAC) of the sentinel lymph node was used as less invasive procedure, but is not accepted as the standard procedure. The goal of this work was to define sensitivity, specification and precision of the ultrasound-guided fine needle aspiration method in comparison with standard sentinel lymph node biopsy. Methods: After obtaining the Ethics Committee's permission, from 2012 to 2014 a total of 60 patients with cutaneous melanoma were enrolled, and divided into three groups: group I with thin melanoma, group II with intermediate thickness melanoma and group III with thick melanoma. The presence of micrometastases in sentinel regional lymph nodes was analyzed by US FNAC. The results obtained were compared to sentinel lymph nodes biopsy (SLNB) results. The golden standard for calculating the specific, sensitive and precise characteristics of the method of US FNAC of sentinel lymph nodes was histopathologic lymph node examination of sentinel lymph nodes acquired through biopsy. Results: Detection rate of US FNAC was 0% in the group I, 5% in the group II and 30% in the group III. SLNB detection rates were: 10% in the group I, 15% in the group II, and 45% in the group III. In melanoma thicker than 4 mm, 15% of the patients were false negative by US FNAC. The sensitivity of US FNAC for all the patients was 50%: in the group I, 0%; in the group II, 33.3%; and in the group III, 66.6%. The method specificity for all examined patients was 100% and accuracy 88%: group I, 90%; group II, 90%; group III, 85%. The FNAC and SLNB micrometastasis detection rate was significantly higher in melanoma with Breslow thickness > 4 mm (group 3) in comparison to thin and intermediate thickness tumors. Conclusion: The method of ultrasound-guided fine needle aspiration of sentinel lymph nodes, according to its sensitivity, has a place in the diagnostics of micrometastasis in regional lymph nodes only in thick melanoma, but not in thin and intermediary thickness melanoma. The results must be confirmed in a larger number of patients. If this observation could be confirmed, it would rationalize treatment of patients with thick melanoma, decrease the number of operations and shorten the time to make the diagnosis.

Acquired cystic disease and renal cell carcinoma in hemodialysis patients--A case report on three patients.

INTRODUCTION: Renal cell carcinoma (RCC) is derived from renal tubular epithelial cells and represents approximately 3.8% of all malignancies in adults. The incidence of renal cell carcinoma has been growing steadily and ranging from 0.6 to 14.7 for every 100,000 inhabitants. Patients with end-stage renal disease and acquired cystic kidney disease are at increased risk of developing RCC while undergoing dialysis treatment or after renal transplantation. CASE REPORT: We presented 3 patients undergoing hemodialysis, with acquired cystic kidney disease accompanied by the development of RCC. In all the patients tumor was asymptomatic and discovered through ultrasound screening in 2 patients and in 1 of the patients by post-surgery pathohistological analysis of the tissue of the kidney excised using nephrectomy. All the three patients had organ-limited disease at the time of the diagnosis and they did not require additional therapy after surgical treatment. During the follow-up after nephrectomy from 6 months to 7 years, local recurrence or metastasis of RCC were not diagnosed. CONCLUSION: Acquired cystic kidney disease represents a predisposing factor for the development of renal cell carcinoma in dialysis patients and requires regular ultrasound examinations of the abdomen aimed at early diagnosis of malignancies. Prognosis for patients with end-stage renal disease and RCC is mostly good because these tumors are usually of indolent course.

Clinical manifestations, therapy and outcome of pandemic influenza A (H1N1) 2009 in hospitalized patients.

BACKGROUND/AIM: Increasing number of epidemiological and clinical studies to date showed that the pandemic influenza A (H1N1) 2009, by its characteristics, significantly differs from infection caused by seasonal influenza. Therefore, the information about clinical spectrum of manifestations, risk factors for severe form of the disease, treatment and outcome in patients with novel flu are still collected. METHODS; A total of 98 patients (mean age 32 +/- 15 years, range 14-88 years) with the signs and symptoms of novel influenza were treated in the Clinic for Infectious and Tropical Diseases, Military Medical Academy. There were 74 (75.5%) patients with suspected influenza A (H1N1) 2009, 10 (10.2%) with the likelihood and 14 (14.3%) with the confirmed influenza. In all the patients we registered the basic demographic data, risk factors for severe disease, symptoms and signs of influenza, laboratory tests and chest radiography. We analyzed antiviral therapy use and disease outcome (survived, died). RESULTS: The average time from the beginning of influenza A (H1N1) to the admission in hospital was 3 days (0-16 days) and from the moment of hospitalization to the Intensive Care Unit (ICU) admission was 2 days (0-5 days). There were 49 (50.0) patients, 20-29 years of age and 5 (5.1) patients older than 65. A total of 21 (21.4%) patients were with underlying disease, 18 (18.4%) were obese, 19 (19.4) were cigarette smokers. All of the patients had fever, 81 (82.6%) cough, while dyspnea and diarrhea were registered in 4 of the patients. In more than 75% of the patients laboratory tests were within normal limits. The real-time polymerase chain reaction (PCR) test for identification of influenza A (H1N1) 2009 was positive in 14 (77.8%), while pneumonia was verified in 30 (30.7%) of the patients. Six (6.1%) patients, mean age of 45 +/- 14 years (31-59 years) were admitted to the ICU, of whom five (5.1%) had Adult Respiratory Distress Syndrome (ARDS). Risk factors were registered more frequently in the patients with acute respiratory failure (14.2% vs 4.9%, p < 0.05). A total of 67 (68.4%) patients received oseltamivir, 89 (90.1%) was applied to antibiotics and 64 (65.3%) were treated with a combined therapy. Antiviral therapy was applied to 43 (43.3%) patients in the first 48 hours from the onset of the disease, of whom only one (3.4) developed ARDS. Fatal outcome was noted in 2.0% of the patients (2 of 98 patients) and in 33.3% of the patients treated in the ICU. CONCLUSION: Novel influenza A (H1N1) is most commonly manifested as a mild acute respiratory disease, which usually affects young healthy adults. A small number of the patients develop severe illness with acute respiratory failure and death. Patients seem to have benefit from antiviral therapy especially in first 48 hours.

[Ultrasonographic findings validity in the identification of metastatic regional lymph nodes in patients with cutaneous melanoma].

UNLABELLED: BACKGROUND/AIM. Early identification of lymph node (LN) metastases has both therapeutic and prognostic significance in patients with cutaneous melanoma. Ultrasonographic (US) examination of LN morphological characteristics and US of LN morphological and vascular characteristics are diagnostic methods used in identification of regional LN metastases, thus rendering a base for lymphonododisection indication. The aim of this study was to determine validity of these two US diagnostic methods and eventual statistically significant difference between them. METHODS. The study included the two groups of the patients with clinical stage III melanoma. The group I included 31 patients followed up by the use of US of LN morphological characteristics due to the fact that US findings described them only. The group II included 30 patients in whom morphological and vascular LN characteristics were followed up. The patients of both groups were examined in the Institute for Radiology, Military Medical Academy using an ultrasonographic unit type Akuson Sequoia Model 2000. After that, therapeutic and elective radical disections were performed. Sensitivity, specificity and accuracy of US examination of LN were checked by histopathological examination. RESULTS: The presence of LN metastases in the group I was suggested by LN enlargement and its extent, while in the group II it was suggested by the ratio of LN length and width in 83.3% of the patients, echogenicity of LN center in 76.7% of the patients, LN resistance index in 73.3% of the patients, pathologic LN vascularization in 86.7%, and pathologic intranodal arborization in 83.3% of the patients. In 67.7% of the patients in the group I and in 93.3% of the patients in the group II matastatic changes of LN were diagnosed by pathohistology. A difference between validities of the two groups was statistically significant (p < 0.05). CONCLUSION: LN size without other US morphological and vascular characteristics of LN does not provide enough valid US finding for a reliable preoperative identification of LN with metastatic changes in patients with cutaneous melanoma.

[Stenting for symptomatic high-grade basilar artery stenosis]. / Stenting simptomatske visokogradusne stenoze bazilarne arterije.

BACKGROUND: Stenosis of brain vessels in 5-10% of cases causes ischemic disesase of the brain. Atherosclerosis is a cause of stenosis in 95% of cases. Patients with basilar artery stenosis and recurrent ischemic attacks are candidate for stroke in 50% of cases in the first two years. CASE REPORT: A 48-year old man presented with a 12-month history of transitory ischemic attacks, periodical loss of vision and balance disorder. Diagnostic cerebral angiography performed by MSCT revealed annular stenosis of basilar artery (85%). Digital subtraction angiography (DSA) confirmed dimensions, grade and localisation of stenosis. Endovascular stenting was performed in general anesthesia. The first step of procedure was preliminary balloon angioplasty and after that self-expandable stent (diameter of 3.0 mm, length of 12 mm) was placed. Check angiogram after stenting confirmed complete dilatation of basilar artery stenosis. CONCLUSION: Combination of balloon angioplasty and self-expandable stenting made possible non-surgical treatment of simptomatic basilar artery stenosis.

[Treatment of degenerative chronic low back pain with fluoroscopically guided epidural procaine-corticosteroid injection].

BACKGROUND/AIM: Low back pain is one of the most common painful conditions in the modern age. Therefore, it is very important to establish the most effective protocol for the treatment of this condition. The aim of this study was to find out if fluoroscopically, guided epidural procaine-corticosteroid injection is effective in the treatment of degenerative chronic low back pain. METHODS: This prospective cohort study was performed in the Military Medical Academy from September 2005 to June 2006 and included 60 patients of both sexes, 34-85 years of age. Degenerative changes of lumbosacral spine were determined by magnetic resonance imaging. The intensity of low back pain was evaluated by subjective (Roland's scale) and objective parameter (Lazarevic sign). Epidural procaine-corticosteroid injection was applied in the patients with low back pain not responding to conservative therapy. After the application of injection, effects of the therapy were followed up. RESULTS: In 92% of the patients there was a reduction of pain intensity for three months, in 4.8% a reduction for a month, but after another injection they felt pain reduction for the next three months. One patient (2.3%) had pain reduction for one month. CONCLUSION: In the treatment of degenerative chronic low back pain, not responding to conservative therapy with nonsteroidal anti-inflammatory drugs, epidural procaine-corticosteroid injection have a satisfactory short-term as well as a long-term analgesic effect.

[Endovascular treatment of carotid-cavernous fistula type A with platinium coils].

BACKGROUND: Carotid-cavernous fistulas are abnormal communications between carotid arteries or their branches and the cavernous system caused mostly by trauma. Posttraumatic fistulas represent 70% of all carotid-cavernous fistulas and they are mostly high-flow shunts (type A). This type gives characteristic eye symptoms. CASE REPORT: This paper presents a 44-year old male patient with carotid-cavernous fistula as a result of penetrating head injury. In clinical presentation the patient had exophthalmos, conjunctival chemosis and weakening of vision on the right eye, headache and diplopia. Digital subtracted angiography showed high-flow carotid-cavernous fistula, which was vascularised from the left carotid artery and from vertebrobasilar artery. Endovascular embolization with platinum coils was performed through the transarterial route (endoarterial approach). Check angiogram confirmed that the fistula was closed and that no new communications developed. CONCLUSION: Embolization of complex carotid-cavernous fistula type A was successfully performed with platinum coils by endovascular approach.

[Diagnosis of multiple myeloma based on the material obtained by fine needle aspiration biopsy of the lungs]. / Dijagnoza multiplog mijeloma na osnovu materijala dobijenog perkutanom iglenom biopsijom pluca.

The patient presented in this paper was admitted to the hospital for the evaluation of radiologically revealed shadow in both lungs. In the course of diagnostic procedures, fine needle aspiration biopsy of the intrathoracic mass was performed. Cytologic analysis of the smear was performed because of clinical suspicion of plasma cell proliferative disease that was confirmed by bone marrow aspiration. Thus, the cytologic finding of intrathoracic lesion preceded the diagnosis of multiple myeloma.