Mitochondria-targeted compounds in the treatment of cancer.

Mitochondria are highly dynamic organelles involved in many cellular functions. Beyond their central role in metabolism, they also take a part in maintaining calcium homeostasis, cell death, immunity, and ROS production. Changes in these functions have been shown to be crucial for the adaptation and survival of cancer cells. Mitochondria, therefore, constitute a promising target for the development of novel anticancer agents. The triphenylphosphonium (TPP+) moiety has been widely used to target molecules into mitochondria. TPP+ derivatives of a variety of conventional cytostatic drugs, natural substances, metformin, antioxidants or a range of newly synthesized molecules have shown promising results against cancer cells. In this review, we discuss biochemical differences between cancer cells and normal cells with a specific focus on mitochondria, and how mitochondrially targeted molecules can be used to selectively affect mitochondrial function in normal and cancer cells. We summarize the published data on mitochondrially targeted anticancer agents and propose future research avenues.

Laparoscopic treatment of bowel perforation after blunt abdominal trauma (BAT) in children.

Minimally invasive techniques have now become standard for the treatment of many surgical conditions in children. There are a few studies that describe the utility of laparoscopy in BAT in children. In this article, we describe the complete laparoscopic surgical treatment of two patients after a single blunt abdominal trauma, both with bowel perforation. In both cases, the perforation was identified and closed, one laparoscopically with an ongoing suture, the second jejune perforation was closed by laparoscopic-assisted techniques. Both patients had an uneventful postoperative recovery. Therapeutic laparoscopic treatment of patients with upper gastrointestinal perforation is feasible. We hypothesize, that diagnostic laparoscopy provides important information for the treatment of children with abdominal trauma and is accompanied by improved diagnostic accuracy, reduction of nontherapeutic laparotomy rates, and a reduction of morbidity. Minimally invasive surgery in children after BAT is suitable for hemodynamic stable patients, could improve pain scores, cosmetic effect, shorter hospital stays, shorter operative times and shorter return to school/activities. However, at any point in the patients care, in case the unstable hemodynamic is encountered, exploratory laparotomy is the procedure of choice.Key words: miniinvasive surgery blunt abdominal trauma - laparoscopy bowel perforation.

[Isolated Perfusion of the Upper Extremity with TNF-α - Double Venous Cannulation]. / Izolovaná perfuze horní koncetiny s TNF-α - dvojitá kanylace zilního systému.

BACKGROUND: The authors present a technical variation of the standard cannulation for cardiopulmonary bypass perfusion during hyperthermic isolated limb perfusion (ILP) procedures in selected patients with unresectable soft tissue sarcoma or malignant melanoma. PATIENTS: Of 55 ILP procedures performed at our institution since the procedure was established in 2009, nine were performed at the upper extremity. Standard single venous cannulation was used in five cases, and extended, double venous cannulation in the last four. The standard technique for brachial vein cannulation in a small compartment of the upper extremity entails a problematic and longer perfusion of the upper extremity. This is due to the lower flow rate in the venous system and relatively large surface area with respect to weight. We present a simple technique based on a "Y" cannulation of the venous system via the deep brachial vein and superficial venous system via the basilic vein, delivering a 20% increase in flow rate in the extracorporeal circulation. Faster heating of the upper extremity and a stable thermal environment throughout upper-extremity ILP are essential for successful treatment. CONCLUSION: Extended technique of venous cannulation for extracorporeal circulation setting, due to their advantages, became standard in the upper limb ILP procedure at our institution.Key words: isolated limb perfusion - malignant melanoma - soft tissue sarcoma - upper limb - extracorporeal circulation The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 8. 1. 2017Accepted: 15. 1. 2017.

Effect of the loading rate on compressive properties of goose eggs.

The resistance of goose (Anser anser f. domestica) eggs to damage was determined by measuring the average rupture force, specific deformation and rupture energy during their compression at different compression speeds (0.0167, 0.167, 0.334, 1.67, 6.68 and 13.36 mm/s). Eggs have been loaded between their poles (along X axis) and in the equator plane (Z axis). The greatest amount of force required to break the eggs was required when eggs were loaded along the X axis and the least compression force was required along the Z axis. This effect of the loading orientation can be described in terms of the eggshell contour curvature. The rate sensitivity of the eggshell rupture force is higher than that observed for the Japanese quail's eggs.

[Hyperthermic Isolated Limb Perfusion Combined with Tasonermin - a Perfusion Leakage Monitoring Technique]. / Hypertermická izolovaná perfuze koncetin v kombinaci s tasonerminem - technika monitorování úniku perfuzátu.

BACKGROUND: Hyperthermic isolated limb perfusion is used to treat irresectable extremity malignancies. It is based on the following principle - the perfusion of the extremity is isolated from systemic circulation and connected to an extra-corporal circuit via which a very high concentration of a chemotherapeutic agent is administered into the blood compartment of the extremity. In some cases, treatment efficiency can be improved using tasonermin (a TNF-α agent). By itself, tasonermin can cause severe health complications in patients if leakage into systemic circulation results in a level that exceeds the maximally tolerated dose. Therefore, it is important to monitor for leakage during the whole operation. METHOD: Leakage monitoring was performed by a nuclear medicine method based on the measurement of activity of a gamma-emitting radiotracer detected by a scintillation probe located over the heart. An amount of radiotracer that resulted in a basal level of measured signal was first administered into the systemic circuit followed by the administration of a second, one order of magnitude higher amount of radiotracer into the perfusion circuit. Leakage, when it occurred, increased the count rate detected over the heart, and the mathematical relation between leakage level and count rate increase was derived. RESULTS: In our department, the method was tested and optimized during isolated limb perfusion without using a TNF-α agent. Then, accreditation for the use of TNF-α was granted. Since then, the method has been used to monitor leakage in all cases of isolated limb perfusion with TNF-α. All isolated limb perfusion operations with TNF-α passed without complications. The radiation burden was almost negligible for both the patient and medical staff. CONCLUSION: The method described in this report represents a reliable method for perfusion leakage monitoring when using TNF-α in our department.Key words: perfusion - isolated limb - TNF-α - leakage - monitoring - nuclear medicine - radiopharmaceuticalsThe authors declare they have no potential confl icts of interest concerning drugs, products, or services used in the study.The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 16. 6. 2016Accepted: 21. 6. 2016.

Hypoxia-related brain dysfunction in forensic medicine.

Blood gases levels imbalances belong to important factors triggering central nervous system (CNS) functional disturbances. Hypoxia can be illness-related, like in many COPD patients, or it may be caused by broad range of external or iatrogenic factors - including influence of drugs depressing respiration, failure to keep the patient's prosthesis-supported airways patent, or a mistake in the operation of medical equipment supporting patient's respiration. Hypoxia, especially when it is not accompanied by rapid carbon dioxide retention, can go unnoticed for prolonged times, deepening existing CNS disorders, sometimes rapidly triggering their manifestation, or evoking quite new conditions and symptoms - like anxiety, agitation, aggressive behavior, euphoria, or hallucinations. Those, in turn, often result in situations raising interest in law enforcement institutions which need forensic medicine specialist's assistance and opinion. The possibility of illness or drug-related hypoxia, especially in terminal patients, is used to raise questions about the patients' ability to properly express their will in the way demanded by law - it also must be considered as a factor limiting the patients' responsibility in case they commit crimes. The possibility of hallucinations in hypoxia patients limits their credibility as witnesses or even their ability to report crime or sexual abuse they have been subjected to.

Biliary atresia - a new derivative method?

BACKGROUND: Biliary atresia is a progressive cholangiopathy in neonates of unknown origin. Surgical intervention - Kasai portoenterostomy - is the only treatment possible. However, only liver transplantation can be considered a definitive solution even in cases of favourable post-operative course, i.e., after bile passage has been recreated. OBJECTIVES: The authors set out to identify ways to optimize the operative treatment in biliary atresia patients. In particular, their objective was to identify a suitable bile derivation area outside porta hepatis, thereby simplifying the surgical procedure of the following liver transplantation. METHODS: The research was conducted from 2006 to 2010 on a set of 30 corrosive casts prepared by the Institute of Anatomy, Medical Faculty, Comenius University Bratislava. The research consisted of an analysis of individual tubular structures of the liver parenchyma, particularly the bile vessels. The authors explored the latter's position and branching out, as well as their relationships in different segments, and their availability in surgical exploration. RESULTS: The analysis of the corrosive casts resulted in selecting an area in liver segments II and III suitable for creating a new type of hepatoenterostomy. The area is sufficiently distant from porta hepatis, conveniently accessible to the surgeon, and has a broad bile duct branch. This type of anastomosis would preserve the anatomic situation in the porta hepatis area intact for the following transplantation. CONCLUSION: While the results of the experiment warrant some optimism, authors will have to wait until this type of derivation operation is applicable in practice. The authors continue their research by performing anastomosis in an animal model (Fig. 5, Ref. 18)

Prevention of neural tube defects by folic acid - awareness among women of childbearing age in Slovakia.

BACKGROUND: Folic acid deficiency plays a central role in the aetiology of many congenital anomalies including neural tube defects. Protective effect of folic acid on embryo may be acquired only if taken periconceptionally. OBJECTIVES: The aim of the study was to investigate the awareness about folic acid among women of childbearing age in Bratislava, Slovakia. METHODS: There were 130 respondents involved in the research (106 pregnant women, 24 female students of medical faculty). Using questionnaire we acquired following data: pregnancy details, interest in diet before and during pregnancy, recommendations regarding nutrition and supplementation pre- and post-conception, knowledge about folic and other acid in 2004 and 2009. RESULTS: More than half of the respondents knew the sources of folic acid. The interest in the nutrition facts of the food dropped from 91 % to 58.5 %. The number of pregnant women advised about correct nutrition and folic acid supplementation before and during pregnancy increased from 16 % to 37 %. Planning the next gravidity with folic acid supplementation became greater than 21 % (38 % in 2009). Nevertheless, only 46 % of these women believed that proper food content with folic acid may prevent congenital anomalies. In a group of students planning to take folic acid periconceptionally the number raised up to 62.5 %. CONCLUSION: The results revealed low knowledge about the effect of folic acid on developing embryo among women of childbearing age. Effective intervention programs are needed with the aim to improve periconceptional intake of folic acid in 2004 and 2009. The results in both periods show low knowledge about this essential vitamin (Tab. 1, Fig. 8, Ref. 31).

Analysis of striatal connectivity corresponding to striosomes and matrix in de novo Parkinson's disease and isolated REM behavior disorder.

Striosomes and matrix are two compartments that comprise the striatum, each having its own distinct immunohistochemical properties, function, and connectivity. It is currently not clear whether prodromal or early manifest Parkinson's disease (PD) is associated with any striatal matrix or striosomal abnormality. Recently, a method of striatal parcellation using probabilistic tractography has been described and validated, using the distinct connectivity of these two compartments to identify voxels with striosome- and matrix-like connectivity. The goal of this study was to use this approach in tandem with DAT-SPECT, a method used to quantify the level of nigrostriatal denervation, to analyze the striatum in populations of de novo diagnosed, treatment-naïve patients with PD, isolated REM behavioral disorder (iRBD) patients, and healthy controls. We discovered a shift in striatal connectivity, which showed correlation with nigrostriatal denervation. Patients with PD exhibited a significantly higher matrix-like volume and associated connectivity than healthy controls and higher matrix-associated connectivity than iRBD patients. In contrast, the side with less pronounced nigrostriatal denervation in PD and iRBD patients showed a decrease in striosome-like volume and associated connectivity indices. These findings could point to a compensatory neuroplastic mechanism in the context of nigrostriatal denervation and open a new avenue in the investigation of the pathophysiology of Parkinson's disease.

Death as a result of violent asphyxia in autopsy reports.

Violent asphyxia can be subdivided into various kinds according to the mechanism, so that the resuscitation techniques are different in each case. The purpose of the present article was to analyze the autopsy reports of the Department of Forensic Medicine of the Medical University in Wroclaw, Poland of 2010, in which the established cause of death was violent asphyxia. We found that among the 890 autopsies performed, there were 164 cases of death due to violent asphyxia caused by drowning, choking on food, gastric fluid, or blood, hanging, manual strangulations, immobilization of the chest (positional asphyxia), environmental asphyxia due to substitution of the oxygen-rich air for some other gas, and others. The most common cause of death in the group was hanging, mostly suicidal hangings of alcohol-intoxicated males. Despite an early medical treatment consisting of removing the noose from the neck and suction the fluids from the mouth and bronchial tree to safe the central nervous system from imminent hypoxia, there were negative outcomes in most cases due to the development of critical brain ischemia, with deaths followed after several days spent in the intensive care units. No connection to gender or age of the deceased was noted. We conclude that violent asphyxia remains to be a quite commonly cause of death in the practice of forensic pathologists - among all the autopsies performed in 2010 every sixth was of an asphyxia victim.

[Metformin: the overlap of diabetology and oncology]. / Metformin: na pomezí diabetologie a onkologie.

Type 2 diabetes moderately increases predisposition for manifestation of tumor disease. Both drugs stimulating insulin secretion (insulin secretagogues) and insulin injection therapy also moderately increases risk of tumor manifestation (OR approx 1.3). According to some reports pyoglitazon therapy could be of increased risk of bladder cancer. On the other hand, hundreds of study on isolated cells, experimental animal models and retrospective studies in patients have shown preventive effect of metformin therapy on manifestation tumors of pancreas, breast, colorectum, liver, endometrium and ovary. More over, the prognosis of diabetic cancer patients on metformin therapy seems be better, than in diabetics without metformin treatment. These data are promising for future use of metformin for prevention and therapy of some malignant tumors.

[Complications resulting from osteosynthesis in children after supracondylar fractures of the humerus]. / Komplikácie vyplývajúce z osteosyntézy suprakondylických zlomenín humeru u detí

INTRODUCTION: The authors carried out the analysis of the causes for re-operations after percutaneous osteosynthesis of supracondylar fractures of the humerus in children. MATERIALS AND METHODS: The authors evaluated the complications of osteosynthesis of supracondylar fractures in children hospitalized at the Clinic of Pediatric Surgery, University Hospital in Bratislava, for a 5-year period between 2007 and 2011. From the total number (395) of supracondylar fractures, 372 were treated as closed reduction and percutaneous transfixation. RESULTS: 32 (8.6%) of supracondylar fractures that were treated as closed reduction and osteosynthesis were indicated for re-operation - 8 times for signs of lesion n. ulnaris, 7 times for migration of Kirschner wires, 17 times for non-anatomical status or osteosynthesis failure. In case of lesions of nervus ulnaris, Kirschner wires were eliminated from the ulnar side and replaced either with intramedullary descendently introduced Kirschner wire to the ulnar condyle (the first option) or with three divergent Kirschner wires from radial side (the second option). In case of failed osteosynthesis, reosteosynthesis was performed using three Kirschner wires (two parallel or divergent from the radial side and one through the medial epicondyle). CONCLUSION: During the period monitored, the introduction of a differentiated approach in the treatment of supracondylar fractures of the humerus in children according to the type of fracture and the degree of displacement has significantly reduced the number of reoperations. Subsequently, it is important to notice that the decreased number of reosteosynthesis can be also assigned to the fact that the initial operation is not necessarily carried out as an urgent one (e.g. by a surgical team on night duty), but can be postponed and performed by an experienced traumatological team next day.

[Fracture-separation of the distal humeral epiphysis in a four-month-old infant: case report]. / Separácia distálnej epifýzy humeru u 4-mesacného dojcata.

We report the case of a 4-month-old infant with fracture-separation of the distal humeral epiphysis diagnosed on the basis of X-ray examination. Closed reduction was performed under ultrasound guidance. The effect of reduction was checked by computer tomography and magnetic resonance imaging and, under general anaesthesia, the arm was immobilised using a collar-and-cuff. Subsequently, percutaneous osteosynthesis with two 1.2-mm Kirschner wires through the radial condyle was carried out. The fracture was allowed to heal in a normal elbow position with plaster cast for 5 weeks. The duration of immobilisation had to be prolonged and removal of the wires postponed because the infant acquired a respiratory infection; the usual time for fracture union is 3 weeks. At 23 months after injury the outcome was excellent and the baby remained registered for a long-term follow-up.

Cell-Tak coating interferes with DNA-based normalization of metabolic flux data.

Metabolic flux investigations of cells and tissue samples are a rapidly advancing tool in diverse research areas. Reliable methods of data normalization are crucial for an adequate interpretation of results and to avoid a misinterpretation of experiments and incorrect conclusions. The most common methods for metabolic flux data normalization are to cell number, DNA and protein. Data normalization may be affected by a variety of factors, such as density, healthy state, adherence efficiency, or proportional seeding of cells. The mussel-derived adhesive Cell-Tak is often used to immobilize poorly adherent cells. Here we demonstrate that this coating strongly affects the fluorescent detection of DNA leading to an incorrect and highly variable normalization of metabolic flux data. Protein assays are much less affected and cell counting can virtually completely remove the effect of the coating. Cell-Tak coating also affects cell shape in a cell line-specific manner and may change cellular metabolism. Based on these observations we recommend cell counting as a gold standard normalization method for Seahorse metabolic flux measurements with protein content as a reasonable alternative.

[Epidemiology of neural tube defects]. / Epidemiológia defektov neurálnej rúry.

INTRODUCTION: Neural tube defects represent group of congenital diseases with relatively high incidence in population. Authors assess world and Slovak literature and statistical facts about the epidemiology of NTD and compare them with their own results of retrospective study performed in Children's Hospital, Bratislava. MATERIALS AND METHODS: List of patients consists of 250 children (106 boys, 144 girls): X-ray images showing lumbo-sacral part of vertebral column were evaluated retrospectively (X-ray of native abdomen, urological tract or skeleton). Authors assessed presence or non-presence of spina bifida on images, without relation to age, gender or diagnosis of patients. RESULTS: From the total number of 250 radiograms, 72 findings were positive (36 boys and 36 girls), 160 images were negative, 18 were unsuitable for evaluation due to low image quality. The highest diagnostic capture was from urological images - 40% of all positive findings. Incidence of spina bifida in Children's Hospital concluded from X-ray images is quite high - 28.8%. CONCLUSION: According to the data from National Centre of Health Statistics the incidence of open caudal neural tube defects in Slovakia is under 5 per 10 000 live-born children at present time. However the occurrence of occult spina bifida is not known exactly. The high rate of spina bifida presented herein (28%) can be caused by relatively low number of evaluated radiograms. Also the fact that children were not only healthy ones and data were obtained from the western part of Slovakia as well. In conclusion we can say that after accidental finding of caudal neural tube defect consecutive diagnostics should be performed in clinical positive cases - genetics, MRI and consultation with specialists to decide for the optimal follow up of the patient.

[Type II bile duct cyst or accessory gall bladder?]. / Cysta choledochu II. typu alebo nadpocetný zlcník?

Choledochal and bile duct's cysts are well known, their morphological classification and also operative management had been described in detail. The most frequent are cysts' types I. and IV., in which the operation consists of cyst's resection and biliary tract reconstruction. Authors summarize nowadays knowledge and present case of 21-months old girl, who was diagnosed of choledochal cyst accidentally. She was operated on electively; the operative finding verified 2 cystic lesions with own bile ducts joined to choledochal duct. The proximal cyst had 3 diverticles and thus mimicked a choledochal cyst type IV. on the preoperative examinations. The resection of both cystic lesions was done. This is a unique case of biliary tract malformations.

Metabolic cooperation in the ovarian follicle.

Granulosa cells (GCs) are somatic cells essential for establishing and maintaining bi-directional communication with the oocytes. This connection has a profound importance for the delivery of energy substrates, structural components and ions to the maturing oocyte through gap junctions. Cumulus cells, group of closely associated GCs, surround the oocyte and can diminished the effect of harmful environmental insults. Both GCs and oocytes prefer different energy substrates in their cellular metabolism: GCs are more glycolytic, whereas oocytes rely more on oxidative phosphorylation pathway. The interconnection of these cells is emphasized by the fact that GCs supply oocytes with intermediates produced in glycolysis. The number of GCs surrounding the oocyte and their age affect the energy status of oocytes. This review summarises available studies collaboration of cellular types in the ovarian follicle from the point of view of energy metabolism, signaling and protection of toxic insults. A deeper knowledge of the underlying mechanisms is crucial for better methods to prevent and treat infertility and to improve the technology of in vitro fertilization.

The role of 18F-DOPA PET/CT in the diagnosis of the congenital focal form of hyperinsulinism in children. / Papel de la PET/TC con 18F-DOPA en el diagnóstico de la forma congénita focal del hiperinsulinismo en niños.

BACKGROUND: Congenital hyperinsulinism (CHI) is a neuroendocrine disease with focal or diffuse abnormalities in pancreas. While drug-resistant diffuse forms require near-total pancreatectomy or prolonged pharmacotherapy, focal CHI may be treated by targeted surgical resection. We evaluated the usefulness of 18F-DOPA PET/CT to identify the focal pancreatic form. SUBJECTS AND METHODS: Nineteen children (11 boys, 8 girls, aged 2-54 months) with clinical signs of neonatal CHI and positive genetic examinations were enrolled in the study. After i.v. administration of 18F-DOPA, early PET and late PET/CT acquisition covering one-bed length over thoraco-abdominal region were performed. Both acquisitions were done in dynamic mode to allow exclusion of frames with motion artefacts. Standardized uptake values were adjusted to bodyweight (SUVbw). The finding was considered as focal when the ratio of SUVbwmax between the suspicious region and the rest of pancreas was greater than 1.2. RESULTS: Focal forms were recorded in 10/19 children and 4 of them underwent surgical resection with complete recovery. Focal uptake was significantly higher than the uptake in the normal pancreatic tissue (p=0.0059). Focal and diffuse forms of CHI did not differ significantly in normal pancreatic tissue uptake. We found no advantage in the measurement of SUVbwmean ratio compared to SUVbwmax ratio (p=0.50). CONCLUSION: 18F-DOPA PET/CT is a useful tool for the localization of focal CHI and planning of surgical treatment.

Comparative study of the substantia nigra echogenicity and 123I-Ioflupane SPECT in patients with synucleinopathies with and without REM sleep behavior disorder.

OBJECTIVES: Hyperechogenicity of the substantia nigra (SN) and abnormal dopamine transporter-single-photon emission computed tomography (DAT-SPECT) are biomarkers commonly used in the assessment of prodromal synucleinopathy. Our goals were as follows: (1) to compare echogenicity of SN in idiopathic rapid eye movement (REM) behavior disorder (iRBD), Parkinson's disease (PD) without RBD (PD-noRBD), PD with RBD (PD + RBD), and control subjects; and (2) to examine association between SN degeneration assessed by DAT-SPECT and SN echogenicity. PATIENTS/METHODS: A total of 61 subjects with confirmed iRBD were examined using Movement Disorders Society-unified PD rating scale (MDS-UPDRS), TCS (transcranial sonography) and DAT-SPECT. The results were compared with 44 patients with PD (25% PD + RBD) and with 120 age-matched healthy subjects. RESULTS AND CONCLUSION: The abnormal SN area was found in 75.5% PD, 23% iRBD and 7.3% controls. Median SN echogenicity area in PD (0.27 ± 0.22 cm2) was higher compared to iRBD (0.07 ± 0.07 cm2; p < 0.0001) and controls (0.05 ± 0.03 cm2; p < 0.0001). SN echogenicity in PD + RBD was not significantly different from PD-noRBD (0.30 vs. 0.22, p = 0.15). Abnormal DAT-SPECT was found in 16 iRBD (25.4%) and 44 PD subjects (100%). No correlation between the larger SN area and corresponding putaminal binding index was found in iRBD (r = -0.13, p = 0.29), nor in PD (r = -0.19, p = 0.22). The results of our study showed that: (1) SN echogenicity area in iRBD was higher compared to controls, but the hyperechogenicity was present only in a minority of iRBD patients; (2) SN echogenicity and DAT-SPECT binding index did not correlate in either group; and (3) SN echogenicity does not differ between PD with/without RBD.

Devastating injury of the groin with vascular lesion.

A 13-year-old girl suffered an injury of the left inguinal region in October 2002. The mechanism of the injury was a fall off a merry-go-round with subsequent trailing by the iron frame, which resulted in devastation of the soft tissues and vessels of her left groin. The patient was transported to the Department of Paediatric Surgery in a state of haemorrhagic shock. A part of the iron frame was still sticking out of her groin. Emergent surgery and haemostasis was followed by reconstructive vascular surgery. Vascular ischaemic-reperfusion syndrome appeared 8.5 hours after the injury. A second episode of haemorrhagic shock developed on the 6th post-operative day, after a dislodgement of an arterial thrombus from a small artery, which was not obvious during the surgery. The situation required emergent wound exploration and surgical control of the bleeding. A third episode of haemorrhagic shock developed on the 9th post-operative day, after an excessive administration of heparin. This time no surgical bleeding was detected during wound exploration. The last episode of haemorrhagic shock appeared 6 months later, during the patient's menarche. She was ashamed to tell her parents about her heavy bleeding for several days. Authors of this article conclude that it is not necessary to increase the dose of Heparin above 20 mcg/kg/hour, even though the value of aPTT is not as high as we would expect. We should expect also the possibility of severe bleeding due to menarche on the anticoagulant therapy in adolescent female patients. Authors also consider both arterial and deep venous reconstructions to be adequate methods of treatment in case of extensive devastating injury of the groin region in the adolescent period (Fig. 5, Ref. 5). Full Text (Free, PDF) www.bmj.sk.