Effect of Alpha Lipoic Acid Supplementation on Oxidative Stress and Lipid Parameters in Women Diagnosed with Low-Grade Squamous Intraepithelial Lesions (LSILs): A Double-Blind, Randomized, Placebo-Controlled Trial.

Limited scientific evidence shows that alpha lipoic acid (ALA) can induce regression rates of low-grade squamous intraepithelial lesions (LSILs), but the mechanisms of these effects have not been elucidated. To gain a broader insight into its therapeutic potential and mechanisms of action, the effects of 3 months of supplementation with 600 mg of ALA on antioxidant and lipid status parameters in 100 patients with LSILs were investigated in a randomized, placebo-controlled study. The obtained results are discussed in terms of patients' initial metabolic status and diet quality (particularly nutritional intake of antioxidants). The obtained results showed that oxidative status biomarkers were not significantly affected by ALA supplementation. However, serum superoxide dismutase (SOD) activity was positively affected in the subgroup of patients with higher dietary antioxidant intake. Surprisingly, ALA supplementation resulted in a small but statistically significant increase in serum low density lipoprotein (LDL), and the observed effect was significantly affected by the initial lipid status of the participants. Larger studies are necessary to gain additional insights on the clinical significance of ALA as an antioxidant and hypolipemic agent and to optimize its potential application in LSIL treatment.

Effect of Alpha-Lipoic Acid Supplementation on Low-Grade Squamous Intraepithelial Lesions-Double-Blind, Randomized, Placebo-Controlled Trial.

Low-grade squamous intraepithelial lesion (SIL) is a cytologic diagnosis etiologically related to human papilloma virus (HPV) infection that leads to the release of inflammation mediators, the formation of reactive oxygen species (ROS) and decreased levels of antioxidants in tissues, which is why antioxidants might be considered effective against SIL progression. This randomized double-blind placebo-controlled study aimed to investigate the effectiveness of alpha-lipoic acid (ALA) supplementation (600 mg/day) on the regression of low-grade SIL in 100 patients. Low-grade SIL was determined after the cytological screening, colposcopic examination and targeted biopsy and histological confirmation of cytological−colposcopic diagnosis. Inflammation parameters and the presence of HPV were determined by standard laboratory methods. Dietary and lifestyle habits were investigated using a standardized and validated semi-quantitative food questionnaire (FFQ). ALA supplementation significantly reduced the proportion of patients with low-grade cytological abnormalities, in comparison to placebo. Given the obtained level of significance (p < 0.001), the presented results indicate that short-term ALA supplementation shows a clinically significant effect on cervical cytology. Future studies should focus on the use of innovative formulations of ALA that might induce bioavailability and therapeutic efficiency against HPV infection and the investigation of synergistic effects of concurrent dietary/lifestyle modification and ALA supplementation in both low-grade and high-grade SIL.

An epidemiological study of neuroendocrine tumours at tertiary hospitals in Bosnia and Herzegovina.

Aim Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumours with varying clinical expression and behaviour. Because of indolent behaviour of NENs, reviewing and evaluation of epidemiological characteristics is a challenge. The aim of this study was to assess prevalence of NENs at tertiary hospitals considering age, gender, location, and grade. Methods Electronic files were used for a retrospective assessment of the patients with NENs of the gastroenteropancreatic tract and bronchopulmonary system in tertiary hospitals in Bosnia and Herzegovina over the past 15 years (2005-2020). Results Among 438 patients, 291(66.4%) were males and 147 (33.6%) females; the median age was 62 years. The lungs were the most frequent site, 304 (69.4%), followed by the pancreas, 22 (5.0%), colon, 14 (3.2%), stomach, 13 (2.9%), appendix, 13 (2.9%), rectum,11 (2.5%), small intestine, eight (1.8%) and gallbladder, one (0.2%). Metastases were most frequently found in the liver, 35 (8%) and lymph nodes, 15 (3.42%). Conclusion The results were largely consistent with those in literature, including age, gender, location, and the degree of differentiation. Most metastases originated from high-grade tumours and greater impairment of the liver.

Prevalence of high-risk human papillomavirus infection and cervical cytology abnormalities among women up to age 40 in the Tuzla Canton, Bosnia and Herzegovina.

INTRODUCTION: Cervical cancer is the second leading cause of female cancer in Bosnia and Herzegovina, and it is the most common female cancer in women 15 to 44 years old. Cervical cancer is etiologically associated with high-risk human papillomaviruses (HRHPV). Data on the prevalence of HRHPV in Bosnia and Herzegovina are scant. This study investigates the prevalence of HRHPV infection among women of reproductive age compared with cervical cytology in the Tuzla Canton. METHODS: We analyzed the results of HRHPV testing and Papanicolaou (Pap) test results in women up to 40 years old diagnosed at the Tuzla University Clinical Center (UCC) from January 2019 to March 2020. RESULTS: Among 880 women tested for HRHPV, 27.2% (n = 239) were ≤ 40 years. In this age group HRHPV was detected in 33.5% (n = 80) of women, and 23.8% (n = 19) were women < 30 years. Out of 239 women tested for HRHPV, 60.2% had an abnormal Pap smear result. Therefore, 40.7% (n = 59) of HRHPV-positive women had an abnormal Pap test result. Women with a normal Pap test result had an HRHPV-positive test in 22.3% (n = 21) of cases. CONCLUSION: The results obtained contribute to the knowledge about HPV prevalence and the incidence of squamous cell abnormalities in the most populous canton in Bosnia and Herzegovina, possibly reflecting the situation nationally. The high prevalence of HRHPV in women of reproductive age calls for urgent implementation of an organized cervical cancer screening program and HPV vaccination.

Clinicopathologic features in a case of intermuscular myopericitoma of thigh.

Myopericytoma is a benign tumor with the most common presentation as a well-circumscribed, slow-growing mass. It is frequently misdiagnosed as a sarcoma. We presented a 23-year-old patient with a history of a sciatic pain of the right leg. A careful physical examination discovered tumor-like mass in the posterior part of the thigh. Neurological finding showed a reduction of myotatic reflexes on the right leg with a weaker muscle strength on the right leg. The right leg musculature was slightly hypotrophic in the range of 2-3 cm comparing to left leg. Initially electrophysiological and radiological diagnostic with magnetic resonance imaging (MRI) of the lumbar spine, pelvis and thighs were normal. Magnetic resonance imaging of the right thigh discovered a slow growing 2.1 × 3.8 cm sized mass that was initially described by radiologist as a neurinoma. Patient was admitted to department of neurosurgery and operated on for a tumor removal. Tumor was located intimately to femur and sciatic nerve and after careful dissection completely removed. Patient was doing well after surgery and discharge after three days from the hospital. In the postoperative period the symptoms disappeared. Histopathology showed a myopericitoma. Postoperative MRI after three months of follow up showed no tumor residues, and after 6 and 12 months there was no tumor recurrence. Myopericytoma behave in a benign fashion, but, because local recurrences and rarely metastases may occur in atypical and malignant neoplasms, a careful follow-up after radical resection is recommended.

Children with Steroid-Resistant Nephrotic Syndrome: A Single -Center Experience.

BACKGROUND: Nephrotic syndrome (NS) is one of the most frequent glomerular diseases among children. While most of the children with primary NS respond to steroid treatment, 10 to 20% of the patients are steroid-resistant, and the best therapy for such cases has never been defined. OBJECTIVE: The present study aimed to evaluate steroid-resistant nephrotic syndrome (SRNS) patients. MATERIALS AND METHODS: Our research included 50 children (56% female and 44% male) with NS. NS was defined as the presence of edema, massive proteinuria, hypoalbuminemia and hyperlipidemia. Patients with NS were treated according to international protocol. SRNS was diagnosed in patients with idiopathic NS based on lack of complete remission despite treatment with steroids. Renal biopsy was performed in 22 patients with SRNS at the Pediatric Clinic II of the University Clinical Center in Sarajevo (UCCS). Histopathologic analyzes of renal biopsy were performed at the Department of Pathology, University Clinical Center in Tuzla (UCCT). Patients with SRNS, after kidney biopsy were treated with nonsteroidal immunosuppressant's. RESULTS: Eight (36.4%) of the 22 patients who had undergone renal biopsies had minimal change disease (MCNS) and seven (31.8%) had focal segmental glomerulosclerosis (FSGS). The immunosuppressive drugs used in SRNS were Cyclosporine (CsA), Cyclophosphamide (CYC), Mycophenolat mofetil (MMF) and Rituximab (RTX). Three patients (13.6%) did not respond to any treatment and had developed end - stage renal disease (ESRD). CONCLUSION: With current treatments, some children will ultimately achieve a sustained remission with one of the second line or third line of the proposed drugs. Patients with refractory NS will go to progression towards ESRD. The rapid development of molecular genetics will give a new contribution to the pathogenesis and treatment of this disease.

Estimate of cervical cancer incidence and mortality rate in Bosnia and Herzegovina.

The exact incidence and mortality rate in Bosnia and Herzegovina are unknown as there are no National Cancer Register. The available data are mostly based on the estimation from neighboring countries. Therefore, the aim of this study was to present the preliminary but more accurate estimates of cervical cancer incidence and mortality rates in Bosnia and Herzegovina. The data on cervical cancer cases in Bosnia and Herzegovina were collected from different sources and varies depending on the size of the city or region. To calculate the crude rates for the period from 2000 to 2008, we used the Bosnian and Herzegovinian population census for 1991. Thus, the crude incidence rate in Sarajevo region is more equable (app. 30.4/100,000 women-year), while in Tuzla Canton it varied from 18.5 in 2005 to 4.8/100,000 in 2000. In Tuzla Canton, in the period 1993-2006, 27.1% of all women with cervical cancer were younger than 30. However, the exact crude incidence in Bosnia and Herzegovina could be even higher. Data from Tuzla Canton showed slight increase in mortality rate in the last 5years (4.9/100,000), with the peak in 2007 (7.0/100,000). The presented data reflects the situation throughout Bosnia and Herzegovina and underline the necessity of the implementation of cervical cancer register and organized screening program.

One hundred kidney transplantations in Tuzla.

INTRODUCTION: Kidney transplantation assures considerably better quality of life than the treatment of end-stage renal disease patients with dialysis. GOAL: Authors intended to present results of kidney transplantations that were performed for over 13 years in UCC Tuzla. EXAMINEES AND METHODS: Total of 100 transplantations have been done over 13 years. The gender and age structure have been presented, as well as number of transplantations per year, type of transplantation (living related donor, living unrelated donor, deceased donor), number and percentage of donors and results of transplantations expressed as survival of both the patient and transplanted kidney/ renal graft. We also wanted to presented other important events such as dates of introduction of certain drugs, dates of first cadaver transplantation, transplantation with desensitization protocols and dates of first living unrelated (spousal/emotional) transplantation. RESULTS: The survival of patients and renal grafts were demonstrated by Kaplan-Meier curve, and obtained results were fully in range of results recommended in other literature and by other authors. One-year survival of graft is 94%, with five-year survival being 75%. One-year survival of patients is 95%, and five-year survival of patients was 84%. DISCUSSION: Our results have been compared to those from other studies, gaining suggestions for transplantation improvement. CONCLUSION: Among all modifications of renal replacement therapy transplantation is by far the method of choice because, its well known advantages aside, it also has an economical advantage over chronic treatment with dialysis and it should therefore become interesting to healthcare systems.

Microscopic polyangiitis presented with polyneuropathy of lower extremities and ANCA-associated glomerulonephritis: case report.

We present the case of a 67-year-old female patient with microscopic polyangiitis presented with polyneuropathy of lower extremities and rapidly progressive glomerulonephritis. Disease had started as a pain and weakening of muscular strength first in the left and than in the right leg. Electromiography has shown that a mainly dominant neurological affection was paresis of peroneal nerve in both lower extremities. In laboratory examination the titer of anti-myeloperoxidase anti-neutrophilic cytoplasmic antibodies (p-ANCA) was elevated. Due to renal involvement presented as a microscopic haematuria and decreasing of renal function, patient undergone kidney biopsy. It confirmed the immune vasculitis microscopic polyangiitis type with ANCA-associated glomerulonephritis. This is one of rare case of microscopic polyangiitis without lung simptomatology, first presented with asymmetrical polineuropathy of lower extremities. The patient was treated with methylprednisolone and cyclophosphamide in dosis adjusted to the level of disease severity and the renal function (methylprednisolone 1 mg/kg of body weight for two months with gradually tapering to the minimum effective dose and cyclophosphamide 1 mg/kg of body weight). This treatment lead to the partial remission of disease. In maintenance therapy azathioprin was introduced instead of cyclophosphamide.

Wegener's granulomatosis of the paranasal sinuses with orbital and central nervous system involvement-diagnostic imaging.

Wegener's granulomatosis (WG) is a systemic vasculitis that can affect any organic system, but primarily involves the upper and lower respiratory tracts and the kidneys. WG relatively frequently affects the nervous system (in 30-50%), usually in the form of peripheral or cranial neuropathy. Involvement of the brain is reported in a very small percentage of patients (2%-8%). Three major mechanisms have been described as the cause of central nervous system (CNS) disease in WG: contiguous invasion of granuloma from extracranial sites, remote intracranial granuloma and CNS vasculitis. CNS involvement caused by contiguous invasion of granuloma from extracranial sites is the rarest. We report the case of a 37-year-old man with WG, manifested as a pulmonary and paranasal sinuses disease, with orbital and CNS involvement, caused by contiguous invasion from the paranasal sinuses. In this report, the rich spectrum of findings achieved by computed tomography and magnetic resonance are demonstrated. The importance of computed tomography in bony destruction PNS findings, and the importance of MR imaging in evaluation of the direct intracranial spread from nasal, paranasal and orbital disease are also emphasized.

Angiosarcoma of the ovary in an 11 year old girl: case report and review of the literature.

Sarcomas of the female genital tract in general are rare and ovarian sarcomas comprise less than 1% of ovarian malignancies. In the literature there are 15 reported angiosarcomas of patients 21 year old and younger with no one originated in the ovary. We report a case of ovarian angiosarcoma in an 11 year old girl, presented with left side hip pain. MRI of abdomen and pelvis confirmed expansive solid and cystic mass occupied both ovaries. Imunohistochemistry staining was performed, CD34, Factor VIII, CD31, in order to confirm the diagnosis. Final diagnosis was angiosarcoma. The patient received 6 cycles of chemotherapy, according to the CWS-2002P protocol. 8 months after the diagnosis was established, there were no signs of any tumors according to the ultrasound, CT scan, and MRI. Although, extremely rare, angiosarcoma can also affect children and this diagnosis should be considered carefully in tumor with rich vascular network, necrosis and brisk mitotic activity.

[Acute rejection in kidney transplantation]. / Akutno odbacivanje u transplantaciji bubrega.

INTRODUCTION: Transplantation of kidneys (TK) is the best way of curing patients with terminal kidney disease. Unfortunately, right after the operation, different kinds of complications are possible and might happen to transplant. The worst and the most often complication is acute rejection (AR). PURPOSE: The aim of work is to find the most often clinical signs and symptoms of AR. The aim of research is to value the influence of AO on function of graft and to find the influence of AR on surviving patients and graft. METHODS: This study has been done on 91 patients, 62 male and 29 female patients in the age of 38.58 +/- 11.4. Patient are divide in two groups: experimental group which includes 29 patients that have had one or more episodes of acute rejection. We used serum concentration of creatinine defined by Cocroft-Gault curve to measure function of transplant. Time of patients and graft survival is estimated by Caplan-Meier curve. RESULTS: In a group of patients with acute rejection we registered 42 episodes of dysfunction of graft which are treated as AR. The average creatinine in a group of patients with acute rejection was 183.42 +/- 65.39 micromol/L. Clearance of creatinine of group patient without AR is much bigger (p < 0.0001) than average clearance of creatinine of patients with acute rejection. Average serum creatinine in this group of patients is 147.59 +/- 62.57 and it is quite smaller (p < 0.002) than average creatinine at patients with acute rejection. Survival of all patients after five years is 91%, survival of patients without acute rejection is 96%, and with acute rejection is 80% (p < 0.014). Five year survival of graft is 78%, at the patients without acute rejection is 96% and at the patients with acute rejection is 64% (p < 0.0001), which is quite shorter. DISCUSSION: Clinical image of acute rejection is unspecific. There is not arranged values of serum creatinine although in some research those values are 130-170 micromol/L. This values includes patients which did not have an acute rejection. Five year survival patients and graft in our patients that did not have an acute rejection is same as in the results of relevant centers. But survival of patients and grafts in patients that had an acute rejection is little bit lower than it is in the results in relevant centers. CONCLUSION: There is no clinical picture than can help you to recognize an acute rejection because many other dysfuncion look the same. Acute rejection reduces function of transplant. Survival of patients and graft is mutch longer in the patients without acute rejection.

Direct immunofluorescence and immunohistochemistry in diagnostics of glomerulonephritis.

The needle biopsies from 60 transplanted and native kidneys have been processed and a prospective analysis of pattern, intensity and distribution of immunoglobulin deposits (IgA, IgG and IgM) and complement components (C3c and C1q) identified in these lesions has been carried out by immunohistochemistry with three step immunoperoxidase, in the period from 2000 to 2004. Those deposits were previously detected and analyzed by immunofluorescence. The samples consisted of 30 renal biopsies, previously diagnosed with glomerulonephritis and positive immunofluorescence and 30 renal biopsies without morphologic changes and deposits on immunofluorescence. 78,7% of the analyzed samples showed the identical results of the deposits of immunoglobulin and components of the complement with both, immunohistochemistry and immunofluorescence method. Sensitivity of the immunohistochemistry method with three step immunoperoxidase for all analyzed immunoglobulin and complement components is high (0,93), while specificity for the same method is 0,79. Standardized method of the three step immunoperoxidase on the paraffin embedded, formalin fixed needle renal biopsies could successfully replace the immunofluorescence method in diagnostic of GN, with the emphasis on a follow up and control of each single step in the procedure of the method.

Association of Hodgkin's lymphoma with Epstein Barr virus infection.

The role of Epstein Barr virus (EBV) in the onset of Hodgkin's lymphoma has been a subject of ongoing research. However, confirmation of EBV oncogenic involvement was not possible due to the small number of neoplastic cells characteristic for this type of tumor. Presence of EBV infection in neoplastic and non-neoplastic cells was analyzed in 81 cases of Hodgkin's lymphoma. In neoplastic cells, using an immunohistochemical method, latent membrane protein 1 (LMP1) was found in 33,3% of cases, while in situ hybridization results demonstrated the presence of EBER RNA in 48,1% of the cases. EBER RNA was found in non-neoplastic lymphocytes in 38,3% of cases. EBV is most frequently associated with Hodgkin's lymphoma in the first and seventh decade of life, specifically the nodular sclerosis subtype. No apparent difference was observed in the association of Hodgkin's lymphoma with EBV between genders, or in relation to clinical stage of the disease and average age of the patient. However, association with childhood age is significantly greater in comparison to adults. EBV associated disease shows a significantly greater prevalence in T lymphocytes. Slightly more abundant are cytotoxic T lymphocytes, which are also more frequently in contact with Reed-Sternberg cells, although there is no difference in number and positioning of histiocytes. Variations between the data on the association of EBV with Hodgkin's lymphoma among studies from different parts of the world suggest that factors of age, gender, ethnic background and social status might present biological modifiers of EBV influence on the pathogenesis of this neoplasm. The differences in non-neoplastic infiltrate EBV+ and EBV- lymphoma indicate the effect of the virus on the immune interaction of tumor and host in this disease.

[Presence of high risk human papilomaviruses (HPV) in the low grade cervical lesion]. / Prisustvo visokorizicnih tipova humanog virusa papiloma (HPV) u niskorizicnim lezijama grlica materice.

UNLABELLED: Low grade squamous intraepithelial lesion (LGSIL) and atypical squamous cells undetermined significance (ASCUS) are the most frequent verified cellular abnormalities. Their management are still highly controversial mostly caused by uncertainty about their histology and nature of originate. Detection of HPV DNA in the absence of cytological abnormalities can also indicate presence of high-grade cervical intraepithelial neoplasia (CIN). The aim of this study was to show the association of the benign cellular changes, ASCUS and LGSIL with oncogenic types of HPV and to prove the necessity of more intensive screening of this group of patients. Cytology and pathomorphology analyses were performed first. Identification of the presence of human papiloma virus was carried out by the Digene Hybride Capture II test for all patients. Identification of different HPV types for the particular number of patients was carried out by RFLP (Rsetriction Fragments Length of Polymorphism). Out of the 101 patients in the first group 92 (91,08%) were HPV positive, and 41, 58% had no cellular abnormalities, ASCUS or LGSIL. Out of 509 patients of the second group 26.92% were positive for HRHPV, and 78,97% of them had no cellular abnormalities, ASCUS or LGSIL. HPV 16 was detected in 27.36% (ASCUS/LGSIL) of low risk cervical lesion of the first examined period. CONCLUSION: The combination of smears with the detection of high risk HPV types increases the triage sensitivity especially at patients with mild.