Paratesticular leiomyosarcoma: A clinical case report.

We present you a Case of 62 year old man with Paratesticular leiomyosarcoma (LMS) localized to the right sctotal half. Detailed pathological and immunohistochemistry characteristic of the tumor was done. For staging was used the classification of French Federation of Cancer Centres Sarcoma Grading System. The final grading of the tumor is grade 3. Paratesticular LMS is rare identity and serves as a diagnostic and treatment challenge.

Overview of the Liulin type instruments for space radiation measurement and their scientific results.

Ionizing radiation is recognized to be one of the main health concerns for humans in the space radiation environment. Estimation of space radiation effects on health requires the accurate knowledge of the accumulated absorbed dose, which depends on the global space radiation distribution, solar cycle and local shielding generated by the 3D mass distribution of the space vehicle. This paper presents an overview of the spectrometer-dosimeters of the Liulin type, which were developed in the late 1980s and have been in use since then. Two major measurement systems have been developed by our team. The first one is based on one silicon detector and is known as a Liulin-type deposited energy spectrometer (DES) (Dachev et al., 2002, 2003), while the second one is a dosimetric telescope (DT) with two or three silicon detectors. The Liulin-type instruments were calibrated using a number of radioactive sources and particle accelerators. The main results of the calibrations are presented in the paper. In the last section of the paper some of the most significant scientific results obtained in space and on aircraft, balloon and rocket flights since 1989 are presented.

Genetic, Genomic and Epigenomic Studies of Balkan Endemic Nephropathy (Ben).

BEN is a primary, chronic tubulointerstitial nephritis characterized with chronic anemia, absence of edema, xantoderma, normal blood pressure and normal findings on the fundus oculi. The disease is distributed in restricted areas in Bulgaria, Romania, Croatia, Bosnia, Former Yugoslavia. Despite numerous studies on genetic and environmental factors and their possible involvement in BEN, its etiopathogenesis still remains elusive. Our recent study aim to elucidate the possible epigenetic component in BEN development. Whole genome DNA array methylation analysis was applied to compare the methylation profiles of male and female BEN patients from endemic regions in Bulgaria and Serbia and healthy controls. All three most prominent candidate genes with aberrations in the epigenetic profile discovered with this study are involved in the inflammatory/immune processes and oncogenesis. These data are in concordance with the reported pathological alterations in BEN. This research supports the role of epigenetic changes in BEN pathology. Exome sequencing of 22.000 genes with Illumina Nextera Exome Enrichment Kit revealed three mutant genes (CELA1, HSPG2, and KCNK5) in BEN patients which encode proteins involved in basement membrane/extracellular matrix and vascular tone, tightly connected to process of angiogenesis. We suggest that an abnormal process of angiogenesis plays a key role in the molecular pathogenesis of BEN.

NGS nominated CELA1, HSPG2, and KCNK5 as candidate genes for predisposition to Balkan endemic nephropathy.

Balkan endemic nephropathy (BEN) is a familial chronic tubulointerstitial disease with insidious onset and slow progression leading to terminal renal failure. The results of molecular biological investigations propose that BEN is a multifactorial disease with genetic predisposition to environmental risk agents. Exome sequencing of 22 000 genes with Illumina Nextera Exome Enrichment Kit was performed on 22 DNA samples (11 Bulgarian patients and 11 Serbian patients). Software analysis was performed via NextGene, Provean, and PolyPhen. The frequency of all annotated genetic variants with deleterious/damaging effect was compared with those of European populations. Then we focused on nonannotated variants (with no data available about them and not found in healthy Bulgarian controls). There is no statistically significant difference between annotated variants in BEN patients and European populations. From nonannotated variants with more than 40% frequency in both patients' groups, we nominated 3 genes with possible deleterious/damaging variants--CELA1, HSPG2, and KCNK5. Mutant genes (CELA1, HSPG2, and KCNK5) in BEN patients encode proteins involved in basement membrane/extracellular matrix and vascular tone, tightly connected to process of angiogenesis. We suggest that an abnormal process of angiogenesis plays a key role in the molecular pathogenesis of BEN.

[Retro and extraperitoneoscopic operations in urology--initial experience].

Retroperitoneoscopic approach is gradually becoming the method of choice in many urologic diseases. In this article we analyse and present the first cases of urological retroperitoneoscopic operations performed in the Department of Urology of the University Hospital "Akeksandrovska". For the period from May 2006 to March 2009 35 extra- and retroperitoneoscopic operations were performed. A 26 retroperitoneoscopic decortications (unroofing) of renal cysts with different localization were performed. 5 pieloplasties without interruption of pieloureteral segment (3 by Fenger method. 2 cases with Y-V pyeloplasty), 2 ureterolithotomies, 1 pyelolithotomy and one radical extraperitoneoscopic prostatectomy. The mean operative time in retro-peritoneoscopscopic decortications of renal cysts was 49.62 minutes (15 to 95 minutes), and in pyeloplasties, ureterolithotomies and pyelolithotomies, mean operative time was 88.00 minutes (65 to 150 minutes). The average pararenal drainage secretion was 138 ml for 24 hours (from 50 ml to 150 ml. The average blood loss was 86 ml (from 50 ml to 120 ml). In one case conversion was required because of technical problems and little experience of the team. Postoperatively in 5 cases (13.51%) we observed subcutaneous emphysema. The benefits of retro-extraperitoneoscopic urological operations are associated with lower morbidity, short stay in hospital, shorter recovery period and less pronounced pain syndrome.

[Local recurrence of the renal cell carcinoma in renal fossa after complete radical nephrectomy. What are the risk factors?].

The local recurrence of the renal cell carcinoma in renal fossa after complete radical nephrectomy is uncommon. According to the latest articles related to this issue it ranges between 2% and 4%. For the period of 1999-2005 we evaluated 11 patients who underwent surgery for isolated renal cell carcinoma recurrence, all of them without clinical presence of distal metastases. 9 of the patients were operated for their first time in our department, and only two in other hospitals. These 9 patients represent 1.41% of the whole number of radical nephrectomies for RCC (637) which took place in our department for the same period of time. The tumor stage of the primary tumor varied from T1 to T3a. In addition lymph node dissection was performed on 7 of the patients. The average time for developing clinically significant fossa recurrence was 18 months. The current article has the purpose to present newer the data for the factors, which may be directly related to the risk of developing local recurrence in the renal fossa after complete radical nephrectomy--the initial tumor stage of the RCC, the relationship between the primary tumor and the histological type of the recurrent masses.

[Could the transrectal prostate biopsy predict the rate of positive lymph nodes in prostate cancer patients?].

Since 1989, when Hodge and al. demonstrated transrectal ultrasound guided prostate biopsy, it has become a "gold standard" for the diagnosis of prostate cancer. According to the experience gained in the period 1999-2003 in the Department of Urology-Medical University, Sofia, in a prospective follow-up of 20 prostate cancer patients, we found relationship between the positive tru-cut biopsy cores and the rate of positive lymph nodes.

Characteristics of progression of early age-related macular degeneration: the cardiovascular health and age-related maculopathy study.

AIMS: To determine the risk of age-related macular degeneration (AMD) progression posed by the presence of each early AMD characteristic. METHODS: A prospective cohort study of 254 participants aged 50 years and older, all with early AMD features at their baseline visit followed for an average of 7 years. Stereoscopic colour fundus photographs were graded for early AMD features using the International Classification System. AMD status was stratified into six exclusive levels along a continuum of disease severity according to drusen type, pigmentary abnormalities, or late AMD. Progression was assessed according to three definitions: a change between or within a severity level, or by side by side grading. RESULTS: The progression rate of early AMD ranged between 3.4 and 4.67% per annum depending upon the definition used. In total, 15 (6%) cases progressed from early AMD to the late complication of AMD. After controlling for age and smoking, cases with soft indistinct drusen at baseline were at a greater risk of progressing from early to late AMD than were cases without this characteristic (OR=3.72, 95%CI 1.20-11.54; P=0.02). CONCLUSION: Our proposed definitions of AMD progression give rates that are consistent with current knowledge of progression and its determinants. Each early AMD characteristic conveys its own risk of progression to an eye, with soft indistinct drusen carrying the greater risk. An international consensus on what defines AMD progression would greatly help the research community when trying to assess the importance of new risk factors and the effectiveness of novel interventions.

Clinical markers in adult offspring of families with and without Balkan Endemic Nephropathy.

Balkan Endemic Nephropathy (BEN) is a kidney disease that progresses slowly. Only a few studies have investigated renal clinical markers in offspring of BEN families before the onset of the disease. This project aimed to determine whether kidney function and structure are altered in BEN offspring compared with non-BEN offspring. The study population consisted of 102 adult BEN offspring and a control group of 99 non-BEN offspring. We collected urine and blood samples, and conducted face-to-face interviews, physical examinations and ultrasound measurements of the kidney. Total protein, albumin, beta2-microglobulin and creatinine in urine, creatinine and urea in serum, and creatinine clearance (CCR) were determined. Two risk factors were assessed: first, the overall status of being an offspring from a BEN family, and second, the specific status of a mother and/or father with BEN. The data were analyzed using linear regression. After adjusting for confounders, we found that kidney length and minimal cortex width in BEN offspring were significantly decreased. Urine concentrations of total protein, albumin, and beta2-microglobulin were higher in BEN offspring. Regarding parental history, the associations were statistically significant only for the offspring of mothers who had BEN, with the exception of minimal cortex width, which showed no parental difference. For CCR, we did not identify a statistically significant effect for BEN offspring status nor for parental history. In conclusion, adult offspring of BEN families can be characterized by shorter kidney length and an increased excretion of albumin, total protein, and beta2-microglobulin, in particular, when the mother had BEN.

Immobilization of cells with nitrilase activity from a thermophilic bacterial strain.

Cells of the moderately thermophilic Bacillus sp. UG-5B strain, producing nitrilase (EC3.5.5.1), which converts nitriles directly to the corresponding acid and ammonia, were immobilized using different types of matrices and techniques. A variety of sol-gel silica hybrids were tested for entrapment and adsorption of bacterial cells as well as chemical binding on polysulphone membranes. Activation of the matrix surface with formaldehyde led to an increase in immobilization efficiency and operational stability of the biocatalysts. Among the supports screened, membranes gave the best results for enzyme activity and especially operational stability, with retention of 100% activity after eight reaction cycles.

Methodology of the Cardiovascular Health and Age-Related Maculopathy (CHARM) Study.

Age-related macular degeneration (AMD) is responsible for the majority of visual impairment in the Western world. Epidemiological studies examining risk factors for AMD are needed to develop strategies for the prevention of blindness from this condition. A number of potentially modifiable risk factors for AMD have been identified; however, only smoking has been a consistent risk factor across the numerous studies. A growing body of evidence suggests that AMD and cardiovascular disease may have common risk factors. The Cardiovascular Health and Age Related Maculopathy (CHARM) Study was established to examine the risk factors for AMD and its progression, in particular risk factors associated with cardiovascular disease. Examining risk factors for prevalent AMD, cases with AMD were compared with age and gender matched controls with no AMD features. For the assessment of AMD progression, the study examined in 2001 and 2002 those participants with early AMD, or age-related maculopathy (ARM), who had undergone baseline examination between 1992 and 1995 and compared the characteristics of those who had progression of AMD with those who did not. The CHARM study involved both ophthalmic and cardiovascular examinations. Standardised clinical eye examination and grading of the macular stereo photographs were used to determine the AMD status and progression. To examine cardiovascular status, carotid artery ultrasound imaging analysis of systemic arterial compliance, augmentation index and pulse wave velocity were performed. The traditional and novel risk factors for CVD such as levels of glucose, cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, fibrinogen, C-reactive protein, immunoglobulins A and M, homocysteine, oxidized LDL and the exposure to the Chlamydia Pneumonia infection were determined. DNA was collected for apolipoprotein E genotyping. The present paper outlines the primary aims of the CHARM study, the methodology involved and the recruitment results.

Is the incidence of Balkan endemic nephropathy decreasing?

Balkan Endemic Nephropathy (BEN) is a non-inflammatory, slowly progressing, familial, primarily tubulo-interstitial, bilateral renal disease that affects rural populations in several Balkan countries. Our study describes a time trend of the incidence of BEN in eight villages of Vratza District, Bulgaria, for the period 1965-1987, based on three various data sets. The data suggest that after the initial peak between 1967 and 1970, the incidence remained quite stable for the period 1970-1984, and declined after 1984. However, the study also demonstrates under-recording of BEN cases and less complete case identification, especially after 1979. Migration of population might also have contributed to an apparent decline in registered cases. We detected cases of BEN in villages that previously were BEN-free. We recommended a rigorous monitoring of BEN in all afflicted countries, before concluding that the incidence of BEN is decreasing.

Molecular classification of human carcinomas by use of gene expression signatures.

Classification of human tumors according to their primary anatomical site of origin is fundamental for the optimal treatment of patients with cancer. Here we describe the use of large-scale RNA profiling and supervised machine learning algorithms to construct a first-generation molecular classification scheme for carcinomas of the prostate, breast, lung, ovary, colorectum, kidney, liver, pancreas, bladder/ureter, and gastroesophagus, which collectively account for approximately 70% of all cancer-related deaths in the United States. The classification scheme was based on identifying gene subsets whose expression typifies each cancer class, and we quantified the extent to which these genes are characteristic of a specific tumor type by accurately and confidently predicting the anatomical site of tumor origin for 90% of 175 carcinomas, including 9 of 12 metastatic lesions. The predictor gene subsets include those whose expression is typical of specific types of normal epithelial differentiation, as well as other genes whose expression is elevated in cancer. This study demonstrates the feasibility of predicting the tissue origin of a carcinoma in the context of multiple cancer classes.

Can the specificity of the FDT for glaucoma be improved by confirming abnormal results?

PURPOSE: To determine whether the specificity of the frequency-doubling technology (FDT) perimeter in the screening mode for glaucoma can be improved by repeating abnormal screening results. METHODS: The FDT perimeter was used in C-20-5 screening mode, and the right eye was tested first. After both eyes were tested, the screening was repeated in eyes with any abnormal visual field defects on FDT perimetry. The printouts were categorized as possible visual field abnormality (zero or one miss), probable visual field abnormality (two to four misses), and definite visual field abnormality (more than five misses). A clinical ophthalmologic examination was conducted on the day of the FDT perimetry screening. RESULTS: Complete data were available for 223 people. The participants ranged in age from 23 to 91 years (mean, 68.5 years; standard deviation. 13.7 years), and 119 (53%) were women. The sensitivity of the FDT perimetry screening was 100%; both cases of glaucoma showed an abnormality on FDT perimetry both times. The specificity improved moderately from the first screening to the second screening. The specificity the first time was 62% (95% confidence interval, 53.1-71.2). The specificity the second time was 68.5% (95% confidence interval, 59.8-77.1). Improvement on FDT perimetry rescreening varied by the language spoken at home. Seven of the 19 non-English speakers without glaucoma improved on rescreening, compared with none of the 23 English speakers (P = 0.002). Seven of the 25 right eyes with FDT perimetry abnormalities both times and no glaucoma had no other detectable diseases. Three of 24 left eyes with FDT perimetry abnormalities both times and no glaucoma had no other detectable diseases. Of the 85 patients who did not have glaucoma but had FDT perimetry abnormalities both times, only one did not have some other detectable disease. DISCUSSION: In summary, the sensitivity for glaucoma of the C-20-5 screening mode is excellent, but a paradigm for screening with the FDT perimeter to improve the overall specificity for glaucoma still must be developed.

Intraocular pressure before and after cataract surgery in participants of the Melbourne Visual Impairment Project.

The purpose of this study was to investigate the effect of cataract surgery on intraocular pressure (IOP) in a cluster-stratified random sample of the population of Victoria, Australia. A total of 3271 participants aged 40 years or older were examined at baseline for the Visual Impairment Project. The baseline study (1992-1994) was followed by a 5-year incidence study The IOP data were compared between participants who had cataract surgery between the two stages of the study and participants with and without cataract at follow up. The IOP was also compared before and after cataract extraction in glaucoma participants. An eligible 89 non-glaucoma and 24 glaucoma participants had cataract surgery between the two time points. The analyses showed that IOP increases with age in non-operated eyes in both glaucoma and non-glaucoma groups. However IOP decreased significantly after cataract surgery in eyes with glaucoma but did not change significantly in non-glaucoma participants.

Balkan endemic nephropathy in Vratza, Bulgaria, 1964-1987: an epidemiologic analysis of population-based disease registers.

Balkan Endemic Nephropathy (BEN), first described in 1956 in Vratza region, Bulgaria, may result from prolonged, chronic exposure to environmental toxicants, but the underlying etiologic factors remain elusive. There has been no recent systematic characterization of the epidemiology of this disease. Recently, it has been suggested that the incidence of the disease is decreasing. We therefore abstracted data from registers of patients in 21 affected villages and the town of Vratza, Bulgaria maintained from 1964 through 1987. In 1964, the prevalence of BEN was 6.0 per 1000 inhabitants; among residents of the affected villages, the prevalence was 12.3 per 1000. From 1965 to 1975 the incidence rate was 0.7 per 1,000 person-years, and from 1976 to 1987 the incidence rate was 0.3 per 1,000 person-years (rate ratio 0.43; p < 0.001). Incidence was much lower in Vratza town; among residents of affected villages, the period-specific rates were 1.7 and 0.8 per 1,000 per year, respectively (rate ratio 0.47; p < 0.01). These trends were consistent across all villages for which registers were maintained. Median survival following registration increased from 2.0 to 5.0 years over the same period (p < 0.001). BEN appears to be decreasing in incidence in this region.

Association of presbyopic correction with changes in visual fields.

The purpose of this study was to investigate the effect of presbyopic correction on changes in visual fields caused by an alteration in outflow of aqueous humour Visual fields were compared before and after introduction of presbyopic correction in participants of the Melbourne Visual Impairment Project. Height and slope of the 'Hill of Vision' were assessed by calculating median thresholds in the four sets of three eccentric points. Analysis of 101 eyes in the study group and 101 eyes in the control group shows higher decrease of the 'Hill of Vision' height in the group of participants who started wearing presbyopic correction, than in the group without presbyopic correction (P = 0.02). Intraocular pressure measured irrespectively of participant's accommodative activity was not significantly different between the two groups at both time points. These data suggest that the use of presbyopic correction is associated with changes in the visual field.

Extracellular xylanase production by two thermophilic alkali-tolerant Bacillus strains in batch and continuous cultures.

Xylanase production of newly isolated thermophilic alkali-tolerant Bacillus sp. strain SP and strain BC was investigated in batch and continuous cultures. Enzyme synthesis was inducible with both strains and was observed only in xylan-containing media. Xylan from oat spelt is a better inducer than xylan from birch for strain Bacillus sp. BC while such difference was not observed for strain SP. Compared with batch cultures xylanase production of both strains increased about two times and its rate became more than four times faster in continuous cultures at a dilution rate of 0.2 h(-1).