Medicina, Volume 47, Issue 8 (August 2011) – 8 articles

More than 5 million people are bitten by venomous snakes annually and more than 100 000 of them die. In Europe, one person dies due to envenomation every 3 years. There is only one venomous snake species in Lithuania – the common adder (Vipera berus) – which belongs to the Viperidae family; however, there are some exotic poisonous snakes in the zoos and private collections, such as those belonging to the Elapidae family (cobras, mambas, coral snakes, etc.) and the Crotalidae subfamily of the Viperidae family (pit vipers, such as rattlesnakes). Snake venom can be classified into hemotoxic, neurotoxic, necrotoxic, cardiotoxic, and nephrotoxic according to the different predominant effects depending on the family (i.e., venom of Crotalidae and Viperidae snakes is more hemotoxic and necrotoxic, whereas venom of Elapidae family is mainly neurotoxic). The intoxication degree is estimated according to the appearance of these symptoms: 1) no intoxication (“dry” bite); 2) mild intoxication (local edema and pain); 3) moderate intoxication (pain, edema spreading out of the bite zone, and systemic signs); 4) severe intoxication (shock, severe coagulopathy, and massive edemas). This topic is relevant because people tend to make major mistakes providing first aid (e.g., mouth suction, wound incision, and application of ice or heat). Therefore, this article presents the essential tips on how first aid should be performed properly according to the “Guidelines for the Management of Snake-Bites” by the World Health Organization (2010). Firstly, the victim should be reassured. Rings or other things must be removed preventing constriction of the swelling limb. Airway/breathing must be maintained. The bitten limb should be immobilized and kept below heart level to prevent venom absorption and systemic spread. Usage of pressure bandage is controversial since people usually apply it improperly. Incision, mouth suction, or excision should not be performed; neither a tourniquet nor ice or heat should be applied. A doctor must monitor respiratory rate, blood pressure, heart rate, renal function, fluid balance, and coagulation status. The only specific treatment method is antivenin – serum with antibodies against antigens of snake venom. Antivenins against pit vipers used in the United States are Antivenin Crotalidae Polyvalent (ACP) and a more purified and hence causing less adverse reactions – Crotalidae Polyvalent Immune Fab (CroFab). In Europe, a polyvalent antiserum against Viperidae family snakes (including the common adder) can be used. Antivenins often may cause severe hypersensitivity reactions because of their protein nature. The bite of the common adder (the only poisonous snake in such countries as Lithuania and Great Britain) relatively rarely results in death; thus, considering the risk of dangerous reactions the antivenin causes itself, the usage of it is recommended to be limited only to life-threatening conditions. Full article

Objective. The pathogenesis of esophageal atresia (EA) remains unknown despite a relatively high incidence of this anomaly in population affecting 1 newborn per 3000 live births. The aim of this study was to examine the relative occurrence of growth factors, their receptors, neuropeptide- containing innervation, and tissue-degradating enzymes – matrix metalloproteinases – in the proximal and distal parts of the esophagus with EA.
Materials and Methods. A histopathological study was conducted on 15 patients with EA. Tissues were processed for NGFRp75, PGP 9.5, TGF-β, FGFR, VEGF, EGFR and MMP-2 by means of biotin-streptavidin immunohistochemistry.
Results. In the control and EA-affected distal esophageal specimens, numerous and abundant NGFR-containing structures were detected, while in the proximal part of the esophagus, a decrease in their number was observed in patients. PGP 9.5 also marked neuronal structures similarly. TGF-β was found only in occasional cells in the EA-affected esophageal specimens, while control material demonstrated moderate to numerous TGF-β-containing structures. Abundance of FGFR and only occasional appearance of VEGF-positive cells were found in both the control and EA-affected material. A moderate number of connective tissue cells in controls contained EGFR. Compared with controls, the number of MMP-2 expressing cells in the EA-affected tissues was decreased in the proximal esophagus.
Conclusions. A decrease in PGP 9.5-containing neuronal structures in the proximal esophagus supports insufficient innervation of this part of the organ in EA. A decrease in MMP-2 positive cells in the esophageal atresia-affected proximal esophagus indicates also a possible decrease of tissue adaptive and regenerative reactions. Low expression of TGF-β and almost the absence of EGFR in the EA-affected specimens may result in disturbances of cell growth, proliferation, and differentiation, indicating a significant role of these substances in morphopathogenesis of EA. FGFR and VEGF seem not to characterize EA pathogenesis. Full article

Background. The reproducibility of day-to-day testing of isokinetic concentric and eccentric muscular actions among adolescent basketball players aged 14 to 16 years and relationships of mean within-subject variation in two isokinetic testing sessions with chronological age, biological maturation (estimated age at peak height velocity), training experience, body size, lower-body morphology, and initial strength performance were evaluated.
Material and Methods. The sample included 27 basketball players who completed replicate test sessions of 5 repetitions of reciprocal concentric and eccentric knee extensions and flexions at 60º s^–1. A randomly selected subsample of 8 players completed a third testing session to confirm reliability estimates.
Results. Coefficients of variation (CV) between sessions 1 and 2 ranged from 8.1% to 17.4%, and intraclass coefficients (ICCs) ranged from 0.72 to 0.89. For sessions 1 and 3, CVs ranged from 3.9% to 6.0%, and ICCs ranged from 0.95 to 0.99. The initial level of strength of eccentric knee flexion (r=–0.43) and eccentric knee extension (r=–0.42) were correlated (P<0.05) with eccentric knee extension within-variation between two sessions. Training experience (r=–0.37, P<0.05) and initial values of concentric knee flexion (r=–0.62, P<0.01) were correlated with concentric knee flexion within-subject differences. Within-subject variation of eccentric knee extension was correlated (P<0.05) with chronologic age (r=0.41), estimated age at peak height velocity (r=–0.38), body size (r=0.41 to 0.47), and leg volume (r=0.39).
Conclusions. Familiarization sessions may improve the reliability of concentric and eccentric knee isokinetic strength testing at 60º s^–1 in adolescent basketball players. Age, maturity status, and training experience of young athletes should be considered when testing knee isokinetic strength at 60º s^–1. Full article

Primitive neuroectodermal tumors are a group of rare, aggressive, and highly malignant embryonal tumors of unknown etiology of the central and peripheral nervous systems. It is a term for a group of small round cell tumors thought to be derived from fetal neuroectodermal precursor cells. Primitive neuroectodermal tumor is usually described as a tumor of children younger than 15 years and is very rare in adults. The article presents a short literature review and a rare case of a primary primitive neuroectodermal tumor of the central nervous system diagnosed in a 51-year-old woman. Full article

Objective. To establish the prevalence and risk factors of erosive esophagitis (EE) and Barrett’s esophagus (BE) among patients routinely referred for upper endoscopy. Material and Methods. A total of 4032 consecutive patients referred to a regional hospital for upper endoscopy due to upper gastrointestinal and/or “alarm” symptoms were examined. Analysis was performed on the prospectively selected patients (40 in each group) with EE of different grades and BE.
Results. EE was diagnosed in 474 patients (11.75%): grade A, in 194 (41%); grade B, in 167 (35%); grade C, in 65 (14%); and grade D, in 48 patients (10%). Increasing severity of erosive esophagitis and presence of its complication – Barrett’s esophagus – were associated with the decreasing prevalence of H. pylori and increasing hiatal hernia size (P<0.05). Male gender (OR, 3.57; 95% CI, 1.12 to 10.62), hiatal hernia >2 cm (OR, 3.73; 95% CI, 1.60 to 8.68), and absence of H. pylori (OR, 4.24; 95% CI, 1.07 to 16.84) were the factors found to be associated with severe EE. The factors associated with BE were as follows: ulcer and/or stricture of esophagus (OR, 11.94; 95% CI, 2.51 to 41.37), age >60 years (OR, 1.06; 95% CI, 1.01 to 1.20), smoking >10 cigarettes per day (OR, 4.62; 95% CI, 1.01 to 12.50), hiatal hernia >2 cm (OR, 5.22; 95% CI, 1.86 to 14.64), and absence of H. pylori (OR, 5.60; 95% CI, 1.38 to 22.72).
Conclusions. The prevalence of EE was found to be low, and the prevalence of BE was found to be very low among routinely endoscoped patients in primary and secondary care settings in a Lithuanian rural area with high H. pylori prevalence. Increasing severity of gastroesophageal reflux disease was associated with the decreasing prevalence of Helicobacter pylori. Full article

The primary objective of this open-label, two chemotherapy arm, phase 4 study was to evaluate the safety and efficacy of newly developed recombinant granulocyte colony-stimulating factor (rG-CSF) used to prevent neutropenia-related complications in patients with metastatic breast cancer treated with docetaxel (75 mg/m2) and doxorubicin (50 mg/m2) or docetaxel (100 mg/m2) alone. Material and Methods. A total of 50 patients who were treated with a maximum of 6 cycles of either docetaxel-doxorubicin (36 patients) or docetaxel alone (14 patients) every 21 days were recruited from 3 centers in Lithuania. All the patients received study medication rG-CSF at a dosage of 5 μg/kg per day (Sicor Biotech UAB, Teva Group) from day 2 of each cycle and continued for minimum 5 days or until absolute neutrophil count reached ≥1.5×109/L. Results. A total of 611 adverse events were reported. Most of them were related to myelotoxic chemotherapy. Two patients withdrew due to adverse events (neuropathy and bone pain). One patient died possibly because of pulmonary thromboembolism. The most frequently reported adverse events related to study drug in the docetaxel-doxorubicin and docetaxel groups were leukocytosis (22% and 21%, respectively), bone pain (19% and 21%, respectively), and headache (8% and 14%, respectively). The incidence of grade 4 neutropenia in both the groups was 47% and 29%, respectively, in all cycles and 42% and 21%, respectively, in cycle 1. The incidence of febrile neutropenia was 8% in cycle 1 and 14% across all cycles. The mean duration of febrile neutropenia was 2.1 days (SD, 1.9) in cycle 1 and 2.14 days (SD 2.0) across all cycles in both the treatment groups. Conclusion. This study provide data that the study drug rG-CSF has the expected safety and could be an efficacious medication to decrease the risk of febrile neutropenia and related complications of myelosuppressive chemotherapy in patients with metastatic breast cancer. Full article

Objective. The aim of this study was to establish C-reactive protein (CRP) levels in serum of patients with lung cancer and chronic obstructive pulmonary disease (COPD) and evaluate the associations of CRP levels with clinicopathological characteristics.
Materials and Methods. In total, 140 persons were included in the study: 43 patients with lung cancer, 34 patients with lung cancer and COPD, 42 patients with COPD, and 21 healthy subjects. CRP analysis was performed with a serum protein analyzer using commercially available highsensitivity reagent kits.
Results. The C-reactive protein levels were significantly higher in the lung cancer patients with or without COPD compared with the COPD patients or the control group (20.42±1.95 and 22.49±2.31 vs. 8.37±0.91 and 2.49±0.47 mg/L, respectively; P<0.01). The patients with advanced lung cancer had higher CRP levels compared with the patients suffering from early stage lung cancer (23.11±1.72 vs. 14.59±2.23 mg/L, P<0.01). The CRP levels were significantly higher in the patients with early stage lung cancer compared with the COPD patients (14.59±2.23 mg/L vs. 8.37±0.91 mg/L, P<0.05). No association was found between CRP and histology, lung function, and smoking status in the patients with lung cancer.
Conclusions. Chronic inflammation plays an important role in both diseases: lung cancer and COPD. However, it seems that inflammation is more pronounced in patients with lung cancer, as the CRP levels were significantly higher in these patients than other groups. Full article

This review describes the recent progress in the field of heat shock protein 90 (Hsp90) inhibitor design. Hsp90 is a heat shock protein with a molecular weight of approximately 90 kDa. Hsp90 is considered a good anticancer target because its inhibition leads to inactivation of its numerous client proteins participating in various signaling and other processes involved in cancer progression. Numerous Hsp90 inhibitors-leads currently tested in clinical trials are presented in this review. Furthermore, this review emphasizes the application of biophysical binding assays in the development of Hsp90 inhibitors. The binding of designed lead compounds to various Hsp90 constructs is measured by isothermal titration calorimetry and thermal shift assay. These assays provide a detailed energetic insight of the binding reaction, including the enthalpy, entropy, heat capacity, and the Gibbs free energy. A detailed description of the binding energetics helps to extend our knowledge of structure-activity relationships in the design of more potent inhibitors. The most active compounds are then tested for their absorption, distribution, metabolism, elimination, toxicity, and activity against cancer cell lines. Full article