Band 5, Heft 6

Minimal residual disease (MRD) predicts the outcome of acute lymphoblastic leukemia (ALL). Flow cytometry (FC) is one of the most sensitive and most applicable methods for MRD diagnostics, but there is still no agreement on the “gold standard” of the method. We tried to optimize flow cytometric MRD detection in T-ALL. Fourteen adults and 11 children with T-ALL and 12 normal bone marrow (BM) donors were enrolled in the study. We found that the most common phenotypic aberrations in T-ALL were TdT and CD99 coexpression on T-cells in BM. Therefore for MRD detection we developed a limited four-color marker panel (TdT/CD7/cCD3/CD19 and CD99/CD7/cCD3/CD2) and a standard analysis strategy. This assay was evaluated on BM of healthy controls. Less than 0.01% TdT+ or CD99 bright T-cells were found in normal BM. MRD was detected in 9 adult patients and 1 child at different time-points of treatment. The average TdT and CD99 mean fluorescence intensity (MFI) value of residual blasts fluctuated during therapy, but it still remained higher than MFI of normal T-cells. Our established MRD detection method differentiated leukemic lymphoblasts with sensitivity in the range of 0.01% and did not give any false positive results in normal BM.

Fascin and EMMPRIN (CD 147) have a demonstrated relationship with the invasion and progression of many tumors. The aim of this study was to analyze fascin and EMMPRIN expression in non-small cell lung carcinoma and their relationship with clinicopathologic features. Fascin and EMMPRIN expression levels were investigated via the immunohistochemistry of paraffin-embedded tissues of 64 patients with non-small cell lung carcinoma, including 46 squamous cell carcinoma and 18 adenocarcinoma patients. The patients were scored on the basis of staining extent and intensity, and were then assigned a combined score. Fascin expression was present in 44 of 46 (95.6%) patients with SCC and 16 of 18 (88.8%) patients with adenocarcinoma. There was a significant correlation between fascin expression and tumor stage in the SCC and adenocarcinoma groups. EMMPRIN expression was observed in all patients with SCC (46 of 46, 100%) and 16 of 18 (88.8%) patients with adenocarcinoma. There was significant correlation between EMMPRIN expression and both tumor stage and diameter in the SCC group, but not in the adenocarcinoma group. This study revealed that high levels of fascin and EMMPRIN expression may indicate the importance of their roles in the progression of non-small cell lung carcinoma and they could be used as prognostic marker for these tumors.

The aim of the present case-control study was to assess the risk factors for Basal cell carcinoma (BCC) in the Montenegrin population. The study group was comprised of 100 consecutive patients with a diagnosis of BCC, while the control group consisted of patients who did not present skin cancer and who were individually matched to the cases by sex and age. The increased risk for BCC was associated with: the presence of nevi (odds ratio [OR] = 3.77; 95% confidence interval [CI] = 1.12–12.73), type of skin concerning to burn rather than to tan after repeated sun exposure in childhood or adolescence (OR = 3.14; 95% CI = 1.59–6.18), the skin reaction to burn after two or more hours of sunlight during childhood or adolescence (OR = 4.53; 95% CI = 2.37–8.63), the number of severe and painful sunburns during their lifetime(OR = 3.52; 95% CI = 1.68–7.38), outdoor work during the summer-time (OR = 2.73; 95% CI = 1.00–7.45), occupational exposure to chemicals (OR = 17.89; 95% CI = 2.82–113.52), history of eczema (OR = 4.17; 95% CI = 1.53–11.39), and history of previous BCC (OR = 3.86; 95% CI = 1.40–10.65). Our study confirms the role of environmental and constitutional factors in development of BCC.

Hidradenitis suppurativa is a chronic, debilitating inflammatory disease of apocrine glands characterized with abscesses and nodular lesions. The treatment of Hidradenitis suppurativa consists of topical antibacterial or antiseptic solutions, systemic antibiotics, steroids, hormonal therapy, anti-tumor necrosis factor, and various surgical procedures. In this report, we present a series of 14 cases with severe Hidradenitis suppurativa. Surgical options are reviewed to show the best outcomes in the long term. A total of 14 patients (9 female, 5 male) were treated for advanced cases of Hidradenitis suppurativa. They underwent excision of the affected regions followed by reconstruction. The reconstruction methods consisted of split-thickness skin grafting and various cutaneous and myocutaneous flaps. There was no flap necrosis or dehiscence. One patient developed contracture in the axilla, for which he underwent release surgery. There were recurrences in 4 cases. There was no limitation of the arm movements in cases with flap reconstruction. In the long-term, they were satisfied with the results. In conclusion, incision and drainage should be avoided because it is of limited value. Surgical removal of the involved tissue should be the first treatment of choice. Depending on the defect following excision, local flaps should be preferred over the grafts for recurrence prevention.

Familial Mediterranean fever (FMF) is a disease of unknown etiology characterized by recurrent attacks of polyserositis and fever. Intercellular adhesion molecule-1 (ICAM-1) is known to contribute inflammatory conditions by regulating leukocyte localization at inflammatory sites. The aim of this study was to evaluate the probable association of ICAM-1 G/R 241 and ICAM-1 E/K 469 polymorphisms according to susceptibility with FMF. Sixty-seven FMF patients and 83 healthy volunteers were included in the study. Genomic DNA was extracted from EDTA-preserved whole blood of whole series of patients and controls, and genotyped by polymerase chain reaction (PCR) and allele-specific oligonucleotide techniques for ICAM-1 polymorphisms G/R at codon 241 and E/K at codon 469. The ICAM-1 241 genotype and allele frequencies of FMF patients and healthy volunteers were similar. The frequency of ICAM-1 K469 homozygosity was significantly lower in FMF patients than in the controls (32.8% vs 50.7% subsequently, p=0.03). Moreover, ICAM-1 E469 allele was more frequent in FMF patients than in controls (44.8% vs 32.3%, p:0.03). Our results showed that ICAM-1 469 gene polymorphism could contribute to the pathogenesis of FMF.

Sepsis remains a serious clinical problems resulting in high morbidity and mortality. We aimed to investigate the inflammatory response in a septic rat model treated with immunomodulator agents. We used the cecal ligature and puncture model to establish septic peritonitis in rats. Male Wistar-Albino rats were randomized into groups of seven rats each and assigned different regimens: Tacrolimus 1 mg/kg/day, cyclosporin-A 5 mg/kg/day and methylprednisolone 15 mg/kg/day. These immunsuppressive agents were applied at the 6 and 48 hour intraperitoneally. The animals were euthanized after 6 and 48 hours and systemic parameters including, IL-2, IL-6, TNF-a, CRP, AST and creatinine were examined. Our study demonstrated that the experimental peritonitis model caused a meaningful rise in the values of systemic parameters. This was especially apparent for early-applied cyclosporin A; in addition, tacrolimus significantly decreased the levels both at the 6 and 48 hour. The excess immune response in complex sepsis treatment might be restrained using immunosuppressive agents administered early. Although additional supportive, comprehensive, experimental and clinical studies are still needed, this therapy model may prove to be an alternative for the future.

Topiramate is an effective drug for the prevention of migraine headaches. On occasion, topiramate can be associated with a dose-related anorgasmia. Presented here is an adult case of reversible anorgasmia induced by and possibly attributable to topiramate therapy. Physicians need to be aware of the potential for topiramate to dose related reversible anorgasmia, and should inquire about sexual symptoms of patients.

The operative deliveries can expose the fetus to acute and systemic hypoxia along with an increase in perinatal morbidity. The aim of this study was to reveal any relationship between delivery type and Chitotriosidase and Troponin T levels in cord blood. Ninety babies born in Ankara Etlik Maternity and Women’s Health Teaching Hospital were involved in the study. The babies were divided into three groups; Group 1: Normal vaginal; Group 2: Caesarean section; Group 3: Forceps application. Cord blood samples were drawn from umbilical arteries of the babies soon after the birth. Chitotriosidase enzyme activities in group 3 (141 nmol/ml/h (0–246)) were found higher than groups 1 (100 nmol/ml/h (0–208)) and 2 (91 nmol/ml/h (0–202)) (p<0.01 and p<0.03 respectively). Although cardiac Troponin T levels were higher in group 3, the difference among groups was not statistically significant (p=0.79). Acute or systemic hypoxic exposure of the organism gives rise to a microvascular response characterized by interactions between leukocytes and endothelium. We are hypothesizing that the high levels of chitotriosidase found in the forceps group were due to hypoxia, and that chitotriosidase level can be used as a marker of acute and systemic hypoxia.

Anal human papillomavirus (HPV) infection commonly affects men who have sex with men (MSM) and is associated with the development of anal cancer, with the highest prevalence in MSM who are positive for human immunodeficiency virus (HIV). The purpose of this study was to determine the prevalence of anal HPV infection and genotype distribution in Slovenian MSM and its correlation with behavioral patterns in order to predict the possible impact of quadrivalent HPV vaccine in this population. To our knowledge, this is the first study of prevalence and genotype distribution of anal HPV infection in MSM from any of the Eastern European countries. The study included 136 MSM who visited two outpatient offices from January 2007 through December 2008. All participants were clinically examined and tested for HIV, and anal swabs were taken for HPV testing. The results showed a high prevalence of anal HPV infection in both HIV-negative (75%) and HIV-positive (95%) MSM. Promiscuity and use of “poppers” (alkyl nitrites taken for recreational purposes through direct inhalation) were clearly associated with a higher prevalence of anal HPV infection. The four most common HPV genotypes were 6, 11, 16, and 18. The prevalence of anal HPV infection in Slovenian MSM is higher in comparison with other studies. Quadrivalent HPV vaccine could have great potential in this population.

Acromegaly is associated with an increased prevalence of colonic polyps. The aim of this study was to evaluate the prevalence and recurrence rate of colonic polyps in acromegalic patients. Ninety-six acromegalic patients and 100 irritable bowel syndrome patients (IBS) were enrolled in the study. Twenty patients who were cured exclusively by surgery, and 20 patients that could not be hormonally controlled were re-examined colonoscopically after 36 months. Twenty-nine of 96 acromegalic patients (30.2%) had colonic polyps. In the IBS group, 10 (10.0%) had colonic polyps. The prevalence of colonic polyps was significantly higher in acromegaly. The group of acromegalic patients with and without polyps did not differ significantly with regard to plasma GH, IGF-I, fasting insulin levels and glycemic status. The presence of colonic polyps was correlated with increased patient age and male gender. We did not observe a difference in terms of polyp recurrence frequencies in the patients cured by surgery compared to uncontrolled patients. Acromegalic patients have a higher prevalence of colonic polyps than that of control subjects. We could not identify any factors that could predict polyps within the acromegalic patients - but age and male sex.

Upper airway resistance syndrome (UARS) is a condition where the apnea-hypopnea index is less than 5 and respiratory-effort related arousal index is more than 10. The clinical presentation of UARS may be the same as obstructive sleep apnea-hypopnea syndrome (OSAS); it sometimes shows up with symptoms hardly suggestive of a sleep-disordered breathing. A 17 year-old male patient had applied to a local psychiatry clinic and complained of chronic fatigue, insomnia, behavioral and academic problems and was treated for anxiety and depression. After a period of unresponsive treatment, he was sent to a sleep center for evaluation of insomnia, which turned out to be a fragmented, unrefreshing sleep episode. Polysomnographical evaluation revealed that he had UARS without OSAS. His complaints decreased dramatically after he received CPAP treatment. This case shows that UARS should be considered in young patients with functional somatic syndromes even if the clinical presentation does not apparently imply the condition.

A 45 year-old man, who had undergone kidney transplantation 7 years prior, was admitted to hospital after a motorcycle accident. The patient was conscious, hemodynamically stable, and had suffered open tibia and femur fractures, as well as closed pubic arm fractures. He had gross hematuria and radiologic study revealed a 3.5 cm length laceration on the transplanted kidney. His renal functions and hematuria recovered after intensive care. He required 2 surgeries for the open fractures but his general condition worsened after the surgical interventions. Acinetobacter, Candida albicans and pseudomonas aeruginosa were determined by blood cultures. Immunosupressive drugs (cyclosporine, prednisolone and azathioprine) were stopped. Despite intensive care, the patient died of sepsis 17 days post trauma. Open fractures of long bones provide a higher risk of sepsis in transplant patients than closed fractures.

Duodenal and jejunal varices usually occur due to portal hypertension and are rare causes of gastrointestinal tract bleeding. We report the case of a patient with no clinically significant history of a coagulopathy disorder, cirrhosis, or portal hypertension who presented with duodenal and jejunal varices that resulted in lower gastrointestinal bleeding with superior mesenteric vein thrombosis. Mesenteric angiography revealed superior mesenteric vein thrombosis and varices at the fourth part of the duodenum and the proximal jejunum draining into the main portal vein, but no active bleeding source was recognized. The patient was hemodynamically unstable. Emergency laparotomy was performed and revealed duodenal and jejunal varices, with occlusion of the superior mesenteric vein. Partial resection of the duodenum and jejunum and end-to-end anastomosis were performed. After surgery, the patient was hemodynamically stable with no recurrence of bleeding.

Morbidity of obesity-related diseases tends to increase due to a rise in the body mass index (BMI). We aimed to investigate how the body composition and biochemical parameters change while BMI increases in adult women were categorized as so: as normal weight, overweight and obese. Our objectives are to study the effects of those changes in the development of metabolic disturbances and to find out which parameters are the most sensitive to predict cardiometabolic risks. Three hundred and twenty two records of adult women (mean age: 38.62±12.71 year) who admitted to our unit concerning about losing or preserving their weights, were analyzed in the study. All patients had undergone anthropometric measurements and body composition analyses as well as some biochemical tests. Body composition analyses were performed by means of the Bioelectrical Impedance Analyzer (BIA). Increase in BMI significantly increased the body fat, blood sugar, insulin, triglyceride and uric acid levels. BMI and circumference of the waist were significantly and negatively correlated with the ratio of body water and lean mass/fat mass. However they were positively correlated with the ratio of fat mass and basal metabolism. Furthermore, it was also found that BMI and circumference of the waist were significantly and positively correlated with level of fasting blood sugar, insulin, triglyceride, homeostasis model assessment insulin resistance (HOMA-IR), uric acid and fibrinogen levels, and negatively correlated with high density lipoprotein (HDL) cholesterol level. In multiple regression analyses, circumference of waist measurements was significantly correlated with insulin, triglyseride and HDL, whereas the correlation between BMI and these parameters was not found significant. Total body fat mass (as %) showed significant correlation only with HDL-C level. It could be said that obesity which is a disorder that causes many health complications and affects the quality of life in the short and long term could be prevented or cured by keeping negative environmental conditions under control. According to our results, visceral adipose tissue (VAT) measurement was thought to be more related for metabolic and cardiovascular disorders rather than BMI. We also propose to test fasting blood glucose, insulin, triglyceride, HDL, fibrinogen, homocystein (HOM) levels along with VAT measurements to predict more truly about not only global cardiometabolic risk but also dementia in later life.

Stevens-Johnson syndrome (SJS) is a rare, life-threatening acute allergic drug reaction presenting with target lesions and blebs of epidermis. Although a variety of etiologies such as infections and underlying malignancies have been implicated as potential causes of SJS, drugs remain the predominant inciting agent. This report presents a SJS case due to combined use of lamotrigine and fluoxetine. A 41-year-old man was admitted to our clinic with fever, skin eruptions (especially on the face and trunk) and lesions around the mouth. The patient’s history revealed lamotrigine and fluoxetine use during the previous three weeks for major depression. Dermatological examination revealed a typical clinical picture of SJS; his psychotropic medications were all stopped. While topical and ocular prednisolone (1mg/kg/day) cares were initiated, steroid dosage was reduced within 15 days. The condition of patient rapidly improved through this treatment. Effective management of SJS begins with prompt recognition of the entity, combined with attention to each of the major organs that may be affected, potential comorbidities and withdrawal of all potentially causative drugs. Clinicians should bear in mind the possibility that drugs with potential risk in developing SJS must be used carefully.

Acute injuries of the tracheobronchial system are rare and life-threatening situations. Tracheal rupture most commonly occurs after blunt trauma to the chest. It is a rare but most concerning immediate complication of intubation. One-lung ventilation is required in lung surgery. Video assisted thoracoscopic procedures are an absolute indication for one-lung intubation. The double-lumen tube is the mainstay of one lung ventilation. Due to their larger size and rigidity, double lumen tubes are more difficult to insert, and complications are more common than with single lumen tubes. Opinions about the need for checking routinely the position of a double lumen tube by fiber optic bronchoscopy directly after intubation are divided. A 69-year-old woman with epidermoid lung carcinoma was scheduled for video assisted thoracoscopic left upper pulmonary lobectomy under general anaesthesia. The patient was prepared for the operation and itubated with the Carlens double lumen tube as usual. On introducing the camera into the thoracic cavity, the surgeon noted that the lungs were not completely collapsed. During blind adjustment the position of the tube the trachea was ruptured. The right-sided thoracotomy was performed and closed the greater part of the tracheal laceration. Only its upper 1.5-cm segment was surgically inaccessible because of the anatomical situation and thus remained unsutured. The patient received antibiotics, continuous airway humidification, analgesia with piritramide, and chest physiotherapy. She had no complications. In the literature, opinions about checking routinely the position of a double lumen tube by fiber optic bronchoscopy are divided.. Possibly, the very serious complication encountered in our patient could have been avoided, had the tube position been checked by bronchoscopy. The treatment strategy for post-intubation tracheal rupture depends on the size and location of the rupture, its clinical presentation, and the overall condition of the patient). Early surgical repair is the treatment of choice for most patients when a transmural tear with a length exceeding 2 cm. In our the combination of surgical and conservative treatment was performed. The uppermost part of the tear could not be sutured because of the anatomical situation, and so about 1.5 cm of the trachea remained open. The case is interesting from many perspectives. It shows that intubation with a Carlens tube is a potentially hazardous procedure, which should be performed only by experienced anaesthesiologists. Furthermore, our case report underscores the importance of checking routinely the position of a double lumen tube by fiber optic bronchoscopy. It provides evidence that minor tracheal lacerations can be successfully managed by conservative measures.

Carpal tunnel syndrome and benign recurrent intrahepatic cholestasis are rare conditions in childhood. Benign intrahepatic cholestasis is characterized by repeated self-limited attacks of cholestasis that can start at any age and last from weeks to months. The patients are asymptomatic between these attacks. We report a 16 year-old male patient with benign recurrent intrahepatic cholestasis who developed carpal tunnel syndrome during a cholestatic attack. He was admitted with complaints of jaundice, pruritus and pain, tingling and muscle weakness in both hands for 15 days. Nerve conduction studies revealed findings compatible with carpal tunnel syndrome. He was started on ursodeoxycholic acid, fat soluble vitamins and cholestyramine and cholestasis regressed after four weeks of therapy. With the improvement of cholestasis, the symptoms of carpal tunnel syndrome also disappeared. In conclusion, benign recurrent intrahepatic cholestasis can be a rare cause of carpal tunnel syndrome in childhood. We also advocate treating the underlying disease as an appropriate conservative treatment before surgery.

To analyze the retinal toxicity of bevacizumab at various doses both in vitrectomized and non-vitrectomized rabbit models. Twenty- eight rabbits were included in the study. Twenty- four rabbits were assigned to six groups, with 4 of the rabbits in the control group. The animals in Groups 1, 2 and 3 received bevacizumab at a dose of 0.3 mg, 0.5 mg and 1.5 mg /eye, respectively. The rabbits in Groups 4, 5 and 6 received intravitreal bevacizumab of 0.3 mg, 0.5 mg and 1.5mg/eye, respectively, after gas compression vitrectomy. Two weeks after the procedure, the rabbits were euthanized. Retina tissue samples were then obtained and examined with both light and electron microscopes. In Groups 1, 2 and 3 after bevacizumab injection, toxic degeneration in the photoreceptor and retinal pigment epithelium cells was observed via electron microscopic examination. The findings in Groups 4 and 5 were normal as compared to the control group. In Group 6, toxicity in the bipolar neurons and photoreceptor cells was noticed. Increased toxicity and retinal penetration were noticed in all administered doses of bevacizumab in the presence of vitreous. In addition, ocular toxicity occurred through the injection of the highest dose of bevacizumab after vitrectomy. It is possible that the bevacizumab dose and the, vitreous are as important as the drug half-life in the vitreous.

Hypovitaminosis D and increased cardiometabolic risk have been well established in adults. This study aims to determine whether or not vitamin D also influences cardiometabolic risk in children and adolescents. To test this hypothesis, we recruited 186 boys (mean age 12.4 ± 3.7 years) and 114 girls (11.6 ± 3.7) in a cross-sectional observational study. Anthropometrics were obtained and morning fasting blood samples were collected. Serum glucose and lipid profile were determined using routine methods. Serum 25-hydroxyvitamin D was quantified using an enzyme-linked immunosorbent assay. In our population, approximately 10% of subjects had severe 25-hydroxyvitamin D deficiency (< 12.5 nmol/L), while 50% of the boys and 40% of the girls had mild vitamin D deficiency (12.5–24.9 nmol/L). Circulating 25-hydroxyvitamin D concentrations were inversely correlated with age, body mass index (BMI), blood pressure, waist and hip circumferences and serum triglyceride concentrations, and positively associated with HDL-cholesterol. Age and systolic blood pressure were significant predictors of 25-hydroxyvitamin D, explaining about 30% of the variance (p = 0.0005). In conclusion, significant associations between serum 25-hydroxyvitamin D and cardiometabolic parameters support promising cardioprotective benefits from vitamin D sufficiency at an early age. Follow-up with prospective clinical intervention studies are needed to validate this hypothesis.

The aim of the study was to investigate the changes in gingival blood flow due to orthodontic forces. Eleven volunteers, with the maxillary canine in an ectopic position were tested. A Laser Doppler Flowmeter (LDF) with a gingival probe was used, registering both the blood flow and temperature of the gingivae. After baseline measurement, a fixed orthodontic appliance was bonded. Measurements were repeated monthly, after activation of the appliance. The study lasted 6 months. The baseline value was 338.7 ± 201.56 P.U. [Perfusion Unit (mean ± S.D.)] which decreased to 218.9 ± 74.83 P.U. (p < 0.05) after two months and the final value of 363.9 ± 194.86 P.U was not significantly different from that initially (p > 0.5). The results showed that application of a force of 75 g resulted in a decrease in gingival blood flow up to 50%, but this returned to previous values after a few months. The study supports this measurement technique as a useful tool for monitoring gingival blood flow in long-term studies as well.