Band 4, Heft 1

Microarray, a miniaturized glass slide or membrane with immobilized DNA probes, is a powerful tool for the analysis of mutations, gene expression and sequencing. This technique requires chip (glass slide or membrane) fabrication, preparation of probes and labelled targets, hybridization and data analysis. Microarrays give the possibility to evaluate a wide spectrum of candidate genes, to simultaneously observe interaction of genes, to detect polymorphisms within genes and identify therapeutic targets. Coronary artery disease being a major cause of death, is a disorder influenced by either genetic or environmental factors. Microarray analysis of gene expression can be used to identify genes involved in disease progression and in disease reduction. Chips also allow for the throughput and simultaneous analysis of a great variety of cell types such as cardiomyocytes, monocytes, macrophages, smooth muscle, endothelial, and fibroblasts and chemical mediators involved in cardiovascular disease pathology, their interactions and cumulative effects.

Neurofibromatosis type I (NF1) is a hereditary multisystem disease involving the skin and nervous system. It is the most common form of autosomal dominant phakomatoses with 100% penetrance but wide phenotypic variability. The NF1 gene is located on chromosome 17q11.2 and encodes for a tumour suppressor protein. Because affected individuals have an increased risk of tumor formation, this disorder is classified as inherited cancer syndrome. The risk of malignancies in NF1 affected patients is estimated to be 5–15% higher than in the general population. We reviewed clinical aspects and genetic mechanisms of tumorigenesis in NF1 affected patients.

We evaluated pressor responses to the hyperventilation test in elderly normotensive (n=43, mean age 82 ± 5 years) and elderly hypertensive subjects (n=45 with essential hypertension, mean age 82 ± 2 years, and n=49 with secondary hypertension, mean age 82 ± 3 years). Hyperventilation did not change blood pressure (BP) in normotensive and secondary hypertensive subjects, whereas it decreased BP in essential hypertensives. Hierarchical cluster analysis based on BP responses to hyperventilation disclosed three groups of subjects in each population: group 1 exhibited a reduction in BP (essential hypertensives: 76%), group 2 no change (normotensives: 70%, secondary hypertensives: 76%), and group 3 an increase (normotensives: 19%, essential hypertensives: 13%, secondary hypertensives: 14%). Ambulatory BP monitoring found significant differences in pressor daytime profiles of hypertensive patients according to pressor responses to hyperventilation showing wide fluctuations in group 1 and 3 patients. Interestingly, the peak ambulatory SBP values correlated to the pre-hyperventilation SBP values in group 1, and to the hyperventilation peak SBP values in group 3. In conclusion: 1) Aging decreases reactivity to respiratory alkalosis in elderly normotensives; 2) hyperventilation induces significant pressor changes frequently in essential hypertension, but rarely in secondary hypertension; 3) the significant pressor responses to hyperventilation reflect the daytime pressor profiles predicting the highest daily fluctuations of BP values.

In the current study, we evaluated the dynamics of oxidative stress markers in patients with acute myocardial infarction (AMI) treated by primary percutaneous coronary intervention (PCI). Thirty consecutive patients with AMI with ST elevation were included. Plasma lipid peroxidation end product malondialdehyde (MDA) and total antioxidant capacity (TAC) in blood plasma were evaluated. Peripheral venous blood samples were obtained prior to reperfusion and at five time points after reperfusion. The control group consisted of 20 ischemic patients without acute coronary syndrome. TAC in the AMI group at admission was lower than in control patients (1.26 + 0.32 vs. 1.52 + 0.24 mmol/l). Within 1 h after reperfusion, in most cases, values significantly declined (1 min, 1.10 + 0.33 mmol/l; 1 h, 1.06 + 0.21 mmol/l [p= 0.03]). After 3 h, values began to increase (1.14 + 0.29 mmol/l) and returned to basal values after 3 d (1.29 + 0.24 mmol/l). MDA levels in AMI patients at admission were higher than in control patients (1.66 + 0.55 vs. 1.44 + 0.55 mmol/l) but showed a sustained decrease over the 3 h after reperfusion of the occluded artery (1 min, 1.57 + 0.37 mmol/l; 1 h, 1.50 + 0.35 μmol/l; 3 h, 1.35 + 0.59 μmol/l [p = 0.03]). Reperfusion of the occluded coronary artery by PCI in AMI lead to an immediate decrease in TAC, suggesting formation of reactive oxygen species. However, the MDA level significantly decreased after reperfusion. This may suggests less reperfusion injury after PCI.

The recent clinical data indicate that the initial and the early stages of chronic renal failure (CRF) may lead to increased incidence of cardiovascular complications and increased extent of coronary artery disease (CAD). This retrospective study was aimed to determine the effects of coexisting diabetes mellitus type 2 (DM-2) and the extent of atherosclerosis in coronary vessels in patients with mildly reduced kidney function (glomerular filtration rate GFR = 89–60 ml/min) and moderately reduced kidney function (GFR = 59–30 ml/min). The study patients included 53 subjects with creatinine concentration above 120 μmol/l as a cut-off level for the initial stage and compensated CRF. The distributions of coronary artery stenosis were also analysed with respect to DM-2 coexistence and levels of haemoglobin glikolised (HbA1c). The odds ratio of pathological changes in coronary arteries in patients with GFR = 44–30 ml/min, with respect to the number of affected vessels — only one, more than one or more than two — were 7.22, 4.90 and 3.55, respectively. In CRF patients with GFR = 60–89 ml/min the odds ratio of one, more than one and more than two vessels with stenosis and CAD was 1.93, 1.70 and 1.53, respectively. DM-2 was not related to the risk of significant coronary artery stenosis and did not enhance the pre-existing changes in the study setting. Our results demonstrate that the initial and the early stages of CRF were significant risk factors for coronary stenoses and for enhancing the pre-existing changes.

The analyses of 18 biochemical parameters (alanine aminotransferase, albumin, aspartate aminotransferase, calcium, cholesterol, chloride, creatinine, iron, glucose, γ- glutamyl transferase, alkaline phosphatase, phosphorus, potassium, sodium, total protein, triglycerides, uric acid, and urea nitrogen) were performed for 166 healthy individuals and 108 patients with end-stage renal failure (ESRF). The application of cluster analysis proved that there were points of similarity among all 18 biochemical parameters that formed major groups; these groups corresponded to the authors’ assumption of the existence of several overall patterns of biochemical parameters that may be termed “enzyme-specific”; “general health indicator”; “major component excretion”; “blood-specific indicator”; and “protein-specific”. These patterns also appear in the subsets of males and females that were obtained by separation of the general dataset. In addition, the performance of factor analysis similarly proved the validity of this assumption. This projection and modelling method indicated the existence of seven latent factors, which explained 70.05% of the total variance in the system for healthy individuals and more than 72% of the total variance in the system for patients with ESRF. All these results support the probability that a general health indicator could be constructed by taking into account the existing classification groups in the list of biochemical parameters.

Solitary rectal ulcer syndrome (SRUS) is a syndrome with symptoms such as rectal bleeding, obstructed defecation, straining at stool and incomplete evacuation, and rectal polyps. In the present study, the clinical features of SRUS among Iranian patients is reviewed. Records of 112 patients diagnosed with SRUS between 1997 and 2007 admitted to a special coloproctology clinic have been analyzed retrospectively. Of 112 patients with SRUS, 61 were male (54.4%) and 51 female (45.6%) with a mean age of 32.2 years (range, 16–64 years). The mean interval between onset of symptoms and final diagnosis of SRUS was 3.8 years (range, 1–14 years). Rectal bleeding (67%) was the most common symptom in both genders, while a feeling of fullness was the least common symptom, observed only in one woman (2%). Incontinence was observed in 4 women (7.8%) and 3 men (4.9%), comprising 6.25% of the total clinical presentations. There were 38 patients (33.9%) with mucosal prolapse and 2 patients (1.8%) with total rectal prolapse. In conclusion, rectal bleeding in the presence of constipation or diarrhea is the main sign for diagnosis of SRUS. This syndrome is usually misdiagnosed; it is frequently confused with inflammatory bowel disease (IBD) because the rectal macroscopic and microscopic lesions and true polyps of rectum are similar. We suggest that most of patients who are treating for IBD and true polyps without any response are suffering from SRUS. Regarding misdiagnosis between SRUS and IBD or rectal polyp, the exact prevalence of SRUS has been mistakenly underestimated.

Uterine leiomyoma with massive lymphoid infiltration is a rare morphologic phenomenon. We describe the first case of uterine leiomyoma with lymphoid infiltration observed in a patient after chemotherapy for sigmoid cancer. We performed immunohistochemical analysis with a panel of antibodies to several markers. Detection of CD20, CD3, Ki67, CD68 and Epstein-Barr virus nuclear antigen assisted in the differential diagnosis and partial elucidation of the pathogenesis. In addition, we examined the lysosome-associated membrane proteins LAMP-1 and LAMP-2 for the first time in this lesion. Their expression was elevated, indicating enhanced autophagy, an indirect sign of degenerative changes in this benign tumor characterized by massive lymphoid infiltration.

The aim of the present study is to evaluate the measurement of midnight salivary cortisol as a method of screening for Cushing’s syndrome (CS). Here we tested the performance of a highly sensitive electrochemiluminescence immunoassay (ECLIA) for midnight salivary cortisol measurement in an extensive clinical study (n=104). Three groups were investigated: 30 patients with CS, 34 with obesity and 40 healthy normal weight controls. All of them collected saliva samples at 24:00 h and urine samples over the same day (24 hour period). An electrochemiluminescence immunoassay was used to measure salivary cortisol. Mean midnight salivary cortisol in healthy volunteers, obese patients and patients with CS was 8.33 ± 3.62, 8.13 ± 4.47 and 33.11 ± 21.68 nmol/l, respectively. No significant difference was found between midnight salivary cortisol in healthy and obese subjects (P>0.05). In contrast, salivary cortisol at midnight was significantly higher in patients with CS (P<0.001) as compared to both other groups. The cut-off point of 14.2 nmol/l yielded a sensitivity of 93.3% and a specificity of 94.2% (AUCROC=0.984 ± 0.01(0.965-1.000). A strong positive correlation between midnight salivary cortisol and urinary free cortisol has been found in the CS group (r=0.686, P<0.0001). Our results demonstrate that measurement of midnight salivary cortisol could be successfully used as a first-line screening method for CS. Our data approve ECLIA as a simple, reliable and timesaving method for the assessment of salivary cortisol. Automated measurement of midnight salivary cortisol by ECLIA would facilitate the routine practice in the screening for CS.

Breast cancer related upper extremity lymphedema (BCRL) reduces the quality of life of those who have had surgery for breast cancer. The aim of this study is to evaluate the risk factors for BCRL and determine whether immediate autologous tissue breast reconstruction is one of them. A case control study was conducted comparing patients with BCRL (n=97) to surgically treated breast cancer patients without BCRL (control, n=126). The groups were matched for age, type of breast surgery and radiation therapy. Postoperative upper extremity infection, body mass index (BMI), occupation (level of hand-use), and immediate autologous tissue breast reconstruction were investigated as a risk factor of BCRL. Mastectomy was performed on 47.6 % (n=60) and 37.2% (n=36) of patients in the control and the BCRL groups, respectively. Eight patients (13.3%) had immediate autologous tissue breast reconstruction in the control mastectomy group. Six of 36 BCRL patients (16.7%) underwent mastectomy with immediate autologous tissue breast reconstruction. There was no significant difference between groups with respect to incidence or method of immediate reconstruction (p=0.65). Patient occupation (level of hand use) was found to be positively correlated to development of BCRL (p=0.0001). Upper extremity infection rate was 22.7% in the BCRL group and 4.0% in the controls (p=0.0001). The mean BMI in the control and BCRL groups 26.8 kg/m2 and 29.1kg/m2, respectively (p=0.003). In conclusion, in this study characteristics positively associated with development of BCRL included occupation, infection, and increased BMI. Immediate reconstruction of the breast was not found as a risk factor for BCRL. However larger studies are needed, to further evaluate the effect of breast reconstruction on BCRL.

The aim of this study was to analyse perinatal complications in woman with increased BMI at pregnancy term. Study included 23190 women who gave singleton birth during a 10-year period in our institution. Maternal databases were reviewed for pregnancy, labor and delivery complications and early maternal postpartum morbidity. Women with increased BMI at pregnancy term had a significantly higer incidence of postterm pregnancy, gestational diabetes, pregnancy-induced hypertension and third trimester hemorrhage, compared to normal weight women (p 0.000). Women with increased BMI had significantly more labor induction with prostaglandins (p 0.001 and 0.000) and elective caesarean (p 0.025 and 0.000). Also, overweight and obese women had higher incidence of operative delivery: caesarean section (p 0.000) and vacuum extraction (p 0.000). The incidences of postpartum febrility (p 0.057, 0.000, 0.002) and trombophlebits (p 0.013) were also significantly higher. We can conclude that prepregnancy normal weight women with increased BMI during pregnancy need special follow-up and counseling in pregnancy and delivery.

The study explores the roles of routine prenatal diabetic screening and control in the occurrence of neurological birth injuries associated with shoulder dystocia. The investigation involved retrospective review of 226 medical records that contained information about the antenatal events in cases that resulted in permanent neonatal injuries following arrest of the shoulders at delivery. Close attention was paid to diabetic screening and management of mothers with evidence of glucose intolerance. Analysis of the records revealed that one-third of all women, including those with predisposing factors, received no diabetic screening during pregnancy. The majority of confirmed diabetic patients were not treated adequately. Among babies of diabetic women, birth weights exceeding 4500 g were about 30-fold more frequent than among those with normal glucose tolerance. The data suggest that universal screening and rigid diabetic control, including mothers with borderline glucose tolerance, are effective measures for the prevention of excessive fetal growth and intrapartum complications deriving from it. If ignored, impaired maternal glucose tolerance may become a major predisposing factor for neurological birth injuries. It appears therefore that with routine screening for diabetic predisposition and effective control of gestational diabetes the risk of fetal damage can be reduced substantially.

The aim of the study was to compare retroorbital blood flow hemodynamics between subconjunctival and sub-Tenon’s anesthesia. This was a prospective, blinded study and included 80 cases. Patients were monitored and treated in the First Ophthalmology Clinic, Ataturk Training and Research Hospital, Turkey. Sub-Tenon’s anesthesia was performed in 42 cases, and subconjunctival anesthesia was performed in 38 cases. Color Doppler imaging to measure ocular blood flow parameters was performed preoperatively and 21 days after cataract operation in each case. Preoperative and postoperative values of resistivity and pulsatility indices in the ophthalmic, central retinal, and short posterior ciliary arteries were compared. Postoperative mean blood flow velocity measurements of ophthalmic artery were not statistically different between the subconjunctival anesthesia group and the sub-Tenon’s anesthesia group (49.63 ± 14.00 vs. 45.85 ± 13.41; P=0.389). Postoperative RI values were higher in the Subtenon’s anesthesia group than in the subconjunctival anesthesia group, but the difference between two groups was not statistically significant (0.81 ± 0.14 vs. 0.74 ± 0.08; P=0.079). The postoperative pulsatility index of the ophthalmic artery, RI of ophthalmic artery, pulsatility index of the central retinal artery, RI of the central retinal artery, and pulsatility index of the posterior ciliary arteries were not significantly different between the subconjunctival and sub-Tenon’s anesthesia groups. In conclusion, the study suggests that postoperative retroorbital blood flow hemodynamics are the same following sub-Tenon’s and subconjunctival anesthesia.

Post-communist Bulgaria has experienced the full impact of a socioeconomic disaster. Under prolonged and powerful stress the human body may exhaust its adaptive potential and a variety of pathophysiological symptoms may occur. The cardiovascular system is most vulnerable to stress. The aim of this study is to analyze the role of psychological factors correlating with Acute Myocardial Infarction (AMI) during the transition period in post-communist Bulgaria. A case-control epidemiological study was performed. 306 cases of acute myocardial infarction (AMI) and 210 controls were studied. Analysis of patients’ records was made and a direct face-to-face interview was carried out. The study covers a 15-year transition period lasting from 1989 until 2005. The interview questions are based on W. Zung’s standardized self-evaluation tests of anxiety and depression (Self Rating Depression Scale — SDS, 1965, SAS-Self Rating Anxiety Scale, 1976) and on a test of aggression, as a part of the Minnesota Multiphase personality inventory, adapted from A.A. Krilov and F. Korozi’s FPI test. Average levels of anxiety and depression appear to be higher among patients suffering from coronary heart diseases than in control group members. Levels of aggression do not show a direct correlation with coronary heart disease. Both groups demonstrate symptoms of psychological disturbances caused, most probably, by the socio-economic instability of the transition period. In conclusion, certain socioeconomic factors significantly increase the level of anxiety and depression in the respondents. The AMI patients are considerably more anxious and depressed than the controls. The results provide evidence that high levels of anxiety and depression may correlate to and be interpreted as a potential risk factor for coronary heart disease.

Dosing pediatric drugs available on pharmaceutical markets of analgesic, antifebrile and anti-inflammatory activity to children up to 3 years of age is not precise and frequently causes problems. The aim of the study was to work out a pediatric teat form of a drug with sodium ibuprofen and to determine the effect of sorbitol content on pharmaceutical availability of the therapeutic agent. Three variants of tablets containing 50 mg of sodium ibuprofen differing in the percentage content of sorbitol (from 37% - batch I to 79% - batch III) were produced. Quality tests of the produced forms of drugs (PPVI) were performed and the tests of therapeutic agent pharmaceutical availability by spatula method and by a method with a teat. Tablets of all batches had a smooth surface and same shape. The content of the therapeutic agent was within the limit of 95-105% of the declared value. The highest value of Q coefficient in the release test by pharmacopeal method and the shortest disintegration time (12 minutes) were obtained for tablets with 79% content of sorbitol. In conclusion, teat tablets with sodium ibuprofen of the highest sorbitol content (79%) demonstrated the expected physicochemical parameters and high pharmaceutical availability.

The study was conducted among 92 male workers, divided into two groups depending on workplace and level of inorganic dust containing free crystalline SiO2 in the work environment, and 43 healthy workers without exposure to dust aerosols. The measured inhalable and respirable dust concentrations, as well as the concentration of free crystalline silica (FCS) in the respirable fraction were different for the two groups, but the percentage of free crystalline silica in the respirable fraction was almost identical. Significantly higher neopterin levels were found in workers exposed to dust, compared to the control group: 12.72 nmol/L and 6.32 nmol/L respectively (p<0.05). No significant difference was found between serum neopterin levels in both groups of the exposed workers. Among the groups with different length of service, a statistically higher neopterin level was evident only in the workers with length of service less than 10 years (p<0.05). The correlation analysis did not find a significant dependence of neopterin levels on the age of the studied workers or on the duration of smoking in packet years. The difference between neopterin levels in smokers and non-smokers was nonsignificant. The results obtained show that increased neopterin levels in the exposed workers are not influenced by individual features, duration and level of exposure to inorganic dust, but mostly by the presence of FCS in the respirable fraction.

This study is aimed to examine the maintenance and utilisation of hearing aids given to clients attending government hospitals in Tshwane and to probe factors that impacted on the hearing aid fitting process, in order to contribute to the formation of service delivery guidelines. As most participants were embarrassed to wear their devices, results showed that there was a general consensus about the self-image and wearing of hearing aids. Furthermore, it was found that most government fitted hearing aids and accessories were poorly cared for and maintained. One of the factors which negatively influenced the utilisation and maintenance of hearing aids was finance. Participants could not afford to properly maintain and service their hearing instruments. Multilingualism also presented an obstacle in terms of utilising hearing aids correctly and to their full benefit, as most participants were not instructed on hearing aid care and use in their first language. Furthermore, distance to and from the provincial hospitals also posed a problem for clients living in rural and outlying areas.

High-residual platelet activity despite the dual antiplatelet treatment with aspirin and clopidogrel is associated with major adverse cardiac events, including stent thrombosis. Acute and subacute stent thrombosis is rare, but presents itself with serious complications including high mortality and morbidity rates. Light transmittance aggregometry with specific agonists — arachidonic acid and 5-adenosin diphosphate — is still considered a standard for the assessment of platelet reactivity, besides novel methods like vasodilator-stimulated phosphoprotein phosphorylation. In our case study, we report the coincidence of high-residual platelet activity with subacute stent thrombosis despite the recommended doses of antiplatelet agents — aspirin and clopidogrel. Stent thrombosis was treated by aspiration thrombectomy, and antiplatelet treatment was modified by increasing the dose of aspirin and substituting clopidogrel with a firstgeneration thienopyridin — ticlopidin. The effect of the treatment was documented by reaching the optimal inhibition of platelet reactivity. In the 6- and 12-month follow-up, the patient presented no ischemic events.

Although foci of calcification in renal cell carcinoma is frequently observed, ossification is extremely rare and may be a marker for favorable prognosis. We report a case of renal cell carcinoma with a focus of ossification; this case was not detected with imaging techniques prior to surgery and diagnosed initially on pathologic examination, unlike other cases. If the radiographic evaluation for ossification is inconclusive but the mass is extremely hard to palpate or difficult to cut, the surgeon should remember the favorable prognosis of such lesions and might consider a limited procedure such as partial nephrectomy while waiting for pathological analysis.

Anatomic anomalies of the biliary tract are not uncommon, but gallbladder and cystic duct agenesis is rare, with an incidence of 0.01% to 0.04% and a frequency of 0.016% at autopsy. It is usually asymptomatic and discovered incidentally. Although this congenital anomaly is infrequent, it may be encountered in clinical practice; thus, the surgeon should be aware of the associated problems. A correct preoperative diagnosis of this congenital anomaly is difficult to establish because of the nonspecific nature of the symptoms and the relative inaccuracy of the currently available diagnostic tests. Here we report a patient with a preoperative false diagnosis of cholelithiasis that was found on laparoscopy and open surgery to be agenesis of the gallbladder.

Various tumours have been reported to metastasise to inguinal lymph nodes. To our knowledge, caecal cancer has never been reported to metastasise to inguinal nodes. We present a case of a woman who had caecal cancer with large contralateral inguinal lymphadenopathy. She underwent right hemicolectomy with excision of the inguinal lymph node. Histology confirmed adenocarcinoma of caecum metastasising to contralateral inguinal lymph nodes.

Anterior intravaginal slingplasty is a widely used procedure for the treatment of stress urinary incontinence. After the operation, defective wound healing, infection, and fistula formation may follow. We present an unusual complication of anterior IVS that is recurrent suprapubic abscess and vaginal fistula formation in a 72-year-old woman. Fistulography was obtained and revealed a fistula tract extending from the suprapubic incision through the entire length of the mesh. Removal of the mesh and obliteration of the fistula tract was performed. Although the symptoms were relieved, the patient started to have episodes of stress urinary incontinence three weeks after the procedure.