Unusual shape and structure of lymphocyte nuclei is linked to hyperglycemia in type 2 diabetes patients.

Type 2 diabetes is an endocrine disorder characterized with hyperglycemia, hyperinsulinemia and insulin resistance. Morphological changes in cell nuclei in diabetes were recently detected. The aim of this study was to compare electron microscopic features of lymphocyte nuclei in type 2 diabetes and healthy individuals using conventional computer assisted methods, fractal analysis and gray level co-occurrence matrix (GLCM) analysis of nuclear chromatin. Mononuclear cells taken from the peripheral blood of newly diagnosed type 2 diabetes patients, metformin treated type 2 diabetes patients and healthy individuals were analyzed with transmission electron microscope. Irregular nuclear contours and lower amount of heterochromatin in lymphocytes were detected with conventional computer assisted methods in type 2 diabetes. Fractal analysis of chromatin structures and GLCM angular second moment (ASM) analysis detected differences in nuclear structure between metformin treated type 2 diabetes and two other groups. Irregularities in lymphocyte nuclei correlated with blood glucose, but not with cholesterol and triglyceride levels. Decrease in fractal dimension, indicating lower level of complexity, increase in GLCM ASM, indicating higher texture uniformity, and higher amount of euchromatin that we found in metformin treated type 2 diabetes could be indicators of higher transcriptional activity in these cells.

Secondary peritonitis - evaluation of 204 cases and literature review.

HYPOTHESIS: Even at the beginning of the new millennium, secondary peritonitis presents a common life-threatening condition associated with high mortality and morbidity. OBJECTIVE: This article comments on epidemiology, diagnosis and general principles of surgical management in patients with secondary peritonitis. METHODS AND RESULTS: The demographic data, clinical findings and surgical outcome of 204 patients who had a confirmed generalized secondary peritonitis were analyzed retrospectively. Our approach was laparotomy, surgical control of contamination, antibiotic therapy and modern intensive care support. Acid peptic disease was the most common cause of perforation peritonitis 60 (29,41%), following by the perforated appendicitis 45 ( 22,06%). The faecal peritonitis and colon perforation were found in 42 patients (20,59%). The morbidity rate was 50%; 41 (40,2%) patients had more than one complication. The morbidity rate was significantly the highest in patients with colon perforation (n=38, 90%) (Hi-square=40,1; p<0,001). The overall mortality rate in our study was 8,82%. The mortality rate was significantly the highest among the patients with mesenteric ischemia in 4 patients (66,67%), followed by colon perforation in 10 cases (23,81%), and 4(6,6%) deaths due to gastro-duodenal perforation (Hi-square=45,7; p<0,001). DISCUSSION: This study has confirmed that the clinical presentation and outcome of the secondary peritonitis depend on duration of abdominal infection, the site of perforation and the general condition of the patient. Rapid surgical source control, modern intensive care and sepsis therapy may offer the chance of decreased morbidity and mortality of the intra-abdominal infections.

Trends in the incidence of hip fractures.

UNLABELLED: Hip fracture incidence in the capital city of Serbia was assessed over a period of 10 years (2000-2009). Crude annual incidence rates increased significantly for all ages and both sexes (p = 0.002). Age-adjusted rates also showed a steady increase. The mean rate of annual change for age-adjusted rates was 8.6 % (95 %CI 7.5-9.7) in males, 8.0 % (95 %CI 7.4-8.6) in females, and 8.2 % (95 %CI 7.7-8.7) in the total population. INTRODUCTION: The aim of this study was to estimate the incidence rate and trend of hip fractures in the population of Belgrade, the capital of Serbia. METHODS: Data sources were the official statistics of the Public Health Institute in Belgrade. The patient's age, gender, residence, hospital admission, and diagnosis were registered for each hospital admission. Population estimates were based on census data from 2002 and on published estimates for the intercensus years. The annual incidence (crude) rates and age- and sex-specific incidence rates were calculated with 95 % confidence intervals (CI) and age-adjusted incidence rates for persons over the age of 50 years were computed. RESULTS: A significantly increasing trend of crude incidence rates for all ages was observed in males (p = 0.002), females (p = 0.001), and overall (p = 0.002). The proportion of trochanteric fractures rose significantly with age in women (p < 0.0001), whereas it decreased nonsignificantly in men ≥70 years (p = 0.44). The age-adjusted incidence rates (per 100,000 in subjects ≥50 years old) showed a steady increase. The mean rate of annual change for age-adjusted rates was 8.6 % (95 %CI 7.5-9.7) in males, 8.0 % (95 %CI 7.4-8.6) in females, and 8.2 % (95 %CI 7.7-8.7) in the total population. CONCLUSION: Hip fracture incidence continues to increase. In view of the rapid aging of the population, it is necessary to implement a comprehensive preventive policy in our community.

[Anesthesiologic care of children with neurologic trauma].

Neurotrauma is a leading cause of childhood mortality. Physicians are in a continuous search for means to decrease mortality and morbidity caused by head injury. Treatment of these patients requires familiarity with both cerebral pathophysiology and actions of anaesthetic agents on brain. Early treatment of hypotension and hypoventilation would cut mortality rate by at least one third. Prevention of increased intracranial pressure is the best treatment for head injury. Anaesthetist, neurosurgeon and radiologist should all be members of a team which can secure timely diagnosis and treatment of an injured child. Paying attention to every detail is of huge significance. Treatment of the child in a pediatric trauma center or an accident and emergencies center for adults with both personnel and equipment capable for handling paediatric patients offers greater probability of survival.

[Open fracture of the shin as an occupational injury and work capacity evaluation--case report].

Injuries at work (occupational injuries) represent a big social and economic problem. This case report presents the patient who suffered occupational injury--open fracture of the left shin. He has been hospitalized for several times at Orthopedic-Surgical Hospital "Banjica" and underwent several surgical procedures, physical therapy and Hyperbaric Oxygen Therapy. After this treatment, he was hospitalized at Institute of Occupational Health for disability evaluation and work capacity evaluation.

[Assessment of perioperative fluid balance].

Careful assessment of the fluid balance is required in the perioperative period since appropriate fluid therapy is essential for successful patient's outcome. Haemodynamic monitoring allows understanding the physiology of the circulation and changes of fluid balance in the perioperative period. This is diagnostic aid and guide for fluid replacement therapy. Patient's volume status is frequently assessed by different haemodynamic variables that could be targeted as the endpoints for fluid therapy and resuscitation. Fluid balance is the crucial factor in the maintenance of haemodynamic stability, tissue oxygenation and organ function. When the haemodynamic monitoring is applied in a rigorous and consistent manner, it reduces mortality and length of stay as well as costs incurred. There are a number of tests which describe the effectiveness of the invasive haemodynamic monitoring procedures usage. Since the pulmonary artery catheter (PAC) had been introduced into clinical practice it was considered as a golden standard for cardiac output measurements, haemodynamic and fluid balance assessment. Nevertheless, in previous 10 years new minimally invasive and noninvasive simple techniques for haemodynamic monitoring and patient's hydroelectricity status evaluation have been developed. They can replace PAC under different clinical circumstances and some of these techniques

AMPK-mediated autophagy inhibits apoptosis in cisplatin-treated tumour cells.

The role of autophagy in cisplatin anticancer action was investigated using human U251 glioma, rat C6 glioma and mouse L929 fibrosarcoma cell lines. A dose- and time-dependent induction of autophagy was observed in tumour cells following cisplatin treatment, as demonstrated by up-regulation of autophagy-inducing protein beclin-1 and subsequent appearance of acridine orange-stained acidic autophagic vesicles. The presence of autophagosomes in cisplatin-treated cells was also confirmed by electron microscopy. Inhibition of autophagy with lysosomal inhibitors bafilomycin A1 and chloroquine, or a PI3 kinase inhibitor wortmannin, markedly augmented cisplatin-triggered oxidative stress and caspase activation, leading to an increase in DNA fragmentation and apoptotic cell death. The mechanisms underlying the protective effect of autophagy apparently involved the interference with cisplatin-induced modulation of Bcl-2 family proteins, as inhibition of autophagy potentiated cisplatin-mediated up-regulation of proapoptotic Bax and down-regulation of anti-apoptotic Bcl-2. Autophagy induction in cisplatin-treated cells was preceded by activation of adenosine monophosphate-activated protein kinase (AMPK) and concomitant down-regulation of mammalian target of rapamycin (mTOR)-mediated phosphorylation of p70S6 kinase. The ability of cisplatin to trigger autophagy was reduced by small interfering RNA (siRNA)-mediated AMPK silencing, while transfection with mTOR siRNA was sufficient to trigger autophagy in tumour cells. Finally, siRNA-mediated AMPK down-regulation and AMPK inhibitor compound C increased cisplatin-induced tumour cell death, while mTOR siRNA and AMPK activator metformin protected tumour cells from cisplatin. Taken together, these data suggest that cisplatin-triggered activation of AMPK and subsequent suppression of mTOR activity can induce an autophagic response that protects tumour cells from cisplatin-mediated apoptotic death.

[Management of cadaveric organ donors].

Because the supply of cadaveric organ donors is limited and their ICU management is complex, a multidisciplinary, well-coordinated, and institutionally supported approach to management is essential to ensure the maintenance of the current supply and to increase the future supply of organs and tissues that are suitable for transplantation. The potential organ donor is at high risk for instability as a direct consequence of the loss of physiologic homeostatic mechanisms that are dependent on functioning of the central nervous system. The keys to successful ICU management of the potential organ donor include a team approach that is focused on the anticipation of complications, appropriate physiologic monitoring, aggressive life support, with frequent reassessment and titration of therapy.

TRAIL induces proliferation of human glioma cells by c-FLIPL-mediated activation of ERK1/2.

TNF-related apoptosis-inducing ligand (TRAIL) induces apoptosis in TRAIL-sensitive human malignant glioma cells. We show for the first time that TRAIL stimulates cell growth in TRAIL-resistant glioma cells. TRAIL-induced cell growth in resistant cells occurred through increased cell cycle progression as determined by flow cytometry and Western blot analysis of retinoblastoma protein phosphorylation. Western blot analysis of TRAIL-treated resistant cells revealed phosphorylation of ERK1/2 proteins and in vitro kinase analysis confirmed the activation of the ERK1/2 kinases. Inhibition of MEK1 eliminated both TRAIL-induced ERK1/2 activation and cell proliferation. In addition, siRNA inhibition of c-FLIP expression eliminates TRAIL-induced ERK1/2 activation and proliferation. Furthermore, overexpression of c-FLIP(L) potentiates TRAIL-induced ERK1/2 activation and proliferation of resistant glioma cells. Our results have shown for the first time that TRAIL-induced ERK1/2 activation and proliferation of TRAIL-resistant human glioma cells is dependent upon the expression of the long form of the caspase-8 inhibitor c-FLIP(L).

[Hemorrhagic shock].

Hemorrhagic shock is a condition produced by rapid and significant loss of blood which lead to hemodynamic instability, decreases in oxygen delivery, decreased tissue perfusion, cellular hypoxia, organ damage and can be rapidly fatal. Despite improved understanding of the pathophysiology and significant advances in technology, it remains a serious problem associated with high morbidity and mortality. Early treatment is essential but is hampered by the fact that signs and symptoms of shock appear only after the state of shock is well establish and the compensatory mechanisms have started to fail. The primary goal is to stop the bleeding and restore the intravascular volume. This review addresses the pathophysiology and treatment of haemorrhagic shock.

[Coagulopaty in associated with massive transfusion].

Massive hemorrhage is a formidable challenge for anesthesia care providers in the elective setting and poses even greater potential challenges in the trauma setting. In all this cases, the anesthesia care providers are faced with large-volume resuscitations that typically start with crystalloid and colloid and rapidly progress to blood and blood products. These large-volume replacement may cause coagulopathy, which can be difficult to manage in the setting of ongoing blood loss. Coagulopathy associated with massive transfusion is multifactorial event that results from hemodilution, hypothermia, the use of fractionated blood products and disseminated intravascular coagulation. Maintaining a normal body temperature is a first-line, effective strategy to improve hemostasis during massive transfusion. Treatment strategies include the maintenance of adequate tissue perfusion, the corection of anemia, and the use of hemostatic blood products.

[Risk factors for bleeding from stress ulcer in severely injured and critically ill persons].

Bleeding stress ulcus is a mucosal stress induced lesion which appears as a result of mucosal damage in severely injured and critically ill persons. Prophylaxis treatment has dramatically reduced the incidence of bleeding in Intensive care units. We conducted a prospective study for the five years period. Of 954 patients (196 with acute necrotizing pancreatitis and 758 with severe injuries), 84 (8.5%) has clinically important bleeding. About 80% of these patients had more than one independent risk for acute bleeding from gastrointestinal tract. Prophylaxis treatment reduced bleeding in 90% risk patients (according Zinner score). Despite of prophylaxis, 13 patients required surgery. Overall mortality was 29 (34%) of 84 patients, including seven of 13 who required surgery. Sepsis and respiratory failure were identified as strong risk factors for bleeding in our group. The choice of the best prophylactic agens still remains the question.

[Surgical perspectives in treatment of bleeding peptic ulcers].

Peptic ulcer bleeding has overall incidence of 50 to 150 on 100.000 grown-ups per year and represents cause for over 1% of all urgent hospitalization today. Despite of the evolution of the endoscopic diagnostics and haemostasis, improved intensive care and surgical treatment, overall mortality is still over 10% (operative treatment over 20%), and it almost hasn't changed over past 40 years. For more than 100 years surgery had major role in treatment of peptic bleeding ulcers, whereas nowadays it is limited to treatment of its complications. Adequate surgical treatment demands properly timed operation, safest but appropriate operation and trained surgeon. Early surgery is much better compared to the last minute surgery. At high risk rebleeding ulcer, early delayed surgery appears to be adequate, since the complications and lethal outcome are more frequent in this group.

[Gastrointestinal gastric tumor (GIST) as a cause of massive hemorrhage from the upper digestive tract].

Gastrointestinal stromal tumors GIST are rare mesenchymal tumors of the gastrointestinal tract characterized by expression of a receptor that activates tyrosine kinase called C- kit. Since malignant GIST has an extremely poor prognosis even after surgical resection. The developement of a tyrosine kinase inhibitor, STI571/imatinib mesylate/Gleevec, Glivec which inhibits the BCR-ABL, PDGF-R alpha, and C-Kit receptors, has changed the management of unresectable malignant GIST and has improved the survival of patients with metastaic disease. We report a 32 year old male patient with subcardiale gastric GIST and massive gastrointestinale bleeding. The patient underwent total gastrectomy, D2 lymphadenestomy, distal pancreatectomy and splenectomy on 02.02. 2004. Histopathology examination of the primary tumor revealed a strong C-Kit expression and CD 34 +++, Ki67 20 and so called "Pure GIST" was approved Liver metastasis was detected on ultrasound and CT 12 months later and segmentectomy S7 was performed on 23.03.2005. Postoperative course was uneventfull. HP examination--malignant 35 x 30 mm sarcoma like tumor of mesenchymal origin. The patient received adjuvant imatinib-mesylate Gleevec Novartis Pharma Basel 400 mg a day. The initial complete response to treatment continued to 24 monts postoperatively Imatinib is a recent and very promising tretemenextirpation remains the only curative treatment of malignant GIST as evideneced by our patient.

[Total gastrectomy in the surgical treatment of acute massive hemorrhage caused by Dieulafoy lesion of the gastric fundus].

GI bleeding caused by Dieulafoy lesion in the gastric fundus: a case report Dieulafoy lesion is a rare cause of massive gastrointestinal (GI) hemorrhage that can be fatal. It arises from an abnormally large eroded submucosal artery and in more than 75% of cases the lesion is mostly found within 6 cm of the cardia. The severity of bleeding and the site of the lesion render the diagnosis sometimes difficult, more than one endoscopic exam is often required. Surgery was regarded as the treatment of choice in the past, but recently endoscopic management has become the standard approach. We report a case of an 42-year-old man presented with upper GI hemorrhage. Repeated upper GI endoscopies revealed a missed diagnosis of subcardial gastric ulcer and Mallory-Weis lesion. Following conservative treatment, the frequency and amount of haemorrhage decreased and totally stop. 48 hours after admission patient developed sudden massive upper GI bleeding and underwent emergency total gastrectomy. The diagnosis of Dieulafoy lesion was made histologically. The patient recovered uneventfully and discharged on the postoperative day 11th. Therefore, Dieulafoy disease represent a diagnostic and therapeutic challenge. Advances in endoscopic technique have greatly assisted in earlier diagnosis and added options to the treatment regimen for this lesion. The relationship of this anomaly to possible exsanguination makes it essential that both endosopical and surgical approach play an important role in the management of this pathology.

Gunshot injury to the face with a missile lodged in the upper cervical spine without neurological deficit.

An unusual case of facial gunshot injury with the missile lodged in the cervical spinal canal, but without any neurological impairment is reported. The extent of tissue damage and missile track termination in a male patient who sustained gunshot trauma to the face was assessed by plain radiography and by CT scans. The patient was treated conservatively and observed for clinical manifestations of neurological deficit for 3 weeks. CT of the head and neck performed 13 years after injury with the three-dimensional (3D) reconstruction of skeletal elements revealed healed fractures of the right nasal bone, the labyrinth of the right ethmoid bone, and position of the missile on the medial aspect of the right lateral mass of the atlas. There was no migration of the missile during this period. This case report of gunshot wound to the face associated with injury of the cervical spine indicated possibility of survival and atypical absence of clinical manifestation that may occur even when a bullet remains in the spinal canal.

[Modern aspects of shoulder injury treatment].

The article describes injuries of soft and bone structures of the shoulder region, with special emphasis on the following clinical forms: instabilities and luxations of the glenohumeral joint, fractures of the proximal humerus, clavicle and the states of painful shoulder. Fractures and dislocations, but also significant entities - painful states caused not only by fractures but also by minor trauma such as tendinitises and m.supraspinatus tendon and bicipital tendon ruptures are discussed in more detail. Moreover, their consequences - painful and stiff shoulder - as well as modern diagnostic and therapeutic procedures applied in the painful shoulder treatment are also discussed.

[Modern aspects of the ankle fracture treatment].

The ankle fractures continue to be a topical issue in orthopedic surgery. X-ray diagnostics, but primarily also other modem diagnostic procedures such as CT, MRI, and arthroscopy enable detection of not only fractures but also osteocartilaginous fractures and soft-tissue ligamentary lesions, which are frequent causes of pain and instability of the ankle. The key segment is the posterio-lateral segment and tibio-fibular syndesmosis whose integrity is sometimes only surgically establishable. In the ankle treatment, stable fixation - since recently by means of resorptive osteofixation materials - and early rehabilitation of the operated ankle are aimed at. The open and pylon fractures, as the most severe forms of ankle fractures, are treated by external fixation with minimum internal fixation (hybrid fixation) of the ankle with conversion of the rigid into a dynamic (articulated) external fixator enabling movement and nutrition of the damaged articular cartilage.

[The treatment of "critical ischemia" of the limbs in endarteritis obliterans by thickening of the tibial bone].

The autors report their experience in the treatment of the "critical ischemia" in 8 patients with arterial occlusion of the lower limbs in endarteritis obliterans. All patients were treated by thickening of the tibia using the Ilizarov apparatus for distraction osteosynthesis. In all cases the operative treatment ensured lowering of the amputation level, forming of the functional stump and long-lasting remission of the illness.

[Nonoperative treatment of fractures of the base of the first metacarpal bone--Bennett fracture].

Although described as early as in 1882, the fracture of the metacarpal bone basis is still a therapeutic challenge for first orthopedic surgeons. Several non-operative and operative methods in the treatment of this fracture have been described. The goal of this paper is to analyze nonoperatively treated patients with Bennett's fracture. A group of 50 patients of both sexes, with the fracture of the first metacarpal bone basis fractures and with the average follow-up of 9 (6-13) years, has been analyzed. After an orthopedic reposition, immobilization lasting 5 weeks was applied, followed by a physical therapy in the duration of 4 to 8 weeks. Numerically, according to Steel, both the subjective and objective state of the hand, as well as an x-ray finding, were assessed. The total hand function was excellent and good in 42 patients, satisfactory in 8, and none of the patients had unsatisfactory function of the hand. Regardless of present degenerative changes, the function of the hand was good, especially if reposition with fragment dislocation less than 2 mm was achieved.