Autophagy of mucin granules contributes to resolution of airway mucous metaplasia.

Exacerbations of muco-obstructive airway diseases such as COPD and asthma are associated with epithelial changes termed mucous metaplasia (MM). Many molecular pathways triggering MM have been identified; however, the factors that regulate resolution are less well understood. We hypothesized that the autophagy pathway is required for resolution of MM by eliminating excess non-secreted intracellular mucin granules. We found increased intracellular levels of mucins Muc5ac and Muc5b in mice deficient in autophagy regulatory protein, Atg16L1, and that this difference was not due to defects in the known baseline or stimulated mucin secretion pathways. Instead, we found that, in mucous secretory cells, Lc3/Lamp1 vesicles colocalized with mucin granules particularly adjacent to the nucleus, suggesting that some granules were being eliminated in the autophagy pathway rather than secreted. Using a mouse model of MM resolution, we found increased lysosomal proteolytic activity that peaked in the days after mucin production began to decline. In purified lysosomal fractions, Atg16L1-deficient mice had reduced proteolytic degradation of Lc3 and Sqstm1 and persistent accumulation of mucin granules associated with impaired resolution of mucous metaplasia. In normal and COPD derived human airway epithelial cells (AECs), activation of autophagy by mTOR inhibition led to a reduction of intracellular mucin granules in AECs. Our findings indicate that during peak and resolution phases of MM, autophagy activity rather than secretion is required for elimination of some remaining mucin granules. Manipulation of autophagy activation offers a therapeutic target to speed resolution of MM in airway disease exacerbations.

[Influence of the Weather on the Incidence of Fractures in the Elderly]. / Vliv pocasí na výskyt zlomenin ve stárí.

PURPOSE OF THE STUDY The incidence of geriatric fractures (proximal femur, distal radius, proximal humerus and thoracolumbar spine injuries) in the population increases with ageing. However, the role of weather conditions, such as icy and slippery winter, should not be overlooked. A deeper insight into this relationship may bring about a better understanding of the fracture aetiology and thus allow for improvement in the prevention of fractures in elderly people. MATERIAL AND METHODS This prospective study included 676 patients (469 women and 207 men) aged 65 and over. Relationships between the incidence of geriatric fractures in these patients and the season, weather phenomena (i.e., air temperature, atmospheric pressure, air humidity, wind speed, visibility, rain, snow, mist and storm) and global biometeorological data in the period from 1 January 2012 to 31 December 2013 were investigated. Patients with high velocity trauma or those with pathological fractures were excluded. Time (day/night), the place of injury (outdoor/indoor/home environment), comorbidities and chronicuse medication were also recorded. Weather forecast records with weather health loads (biotropic indices) were obtained from the commercial service Weather Underground and the Czech Hydrometeoro-logical Institute. The results were statistically analysed using the Statistika 12 programme. RESULTS The incidence of fractures was higher in winter months but there was no statistically significant correlation between the number of fractures and various weather characteristics (temperature, atmospheric pressure, air humidity, wind speed, visibility, rainfall, snow, mist or storm). On the other hand, a relationship between the incidence of geriatric fractures and the biometeorological data (biotropic index) for that day was significant (r = 0.65, p= 0.0401). The majority of fractures occurred during the daytime (83.7%) and in the indoor environment (83.1%); of the latter fractures, 85.2% were home injuries. The most frequent comorbidities included cardiovascular disease (36.2%), obesity (31.1%) and diabetes mellitus (25.4%). DISCUSSION Studies investigating seasonal patterns in relation to the incidence of geriatric fractures are contradictory. Sixteen previous studies have examined seasonal variations and the incidence of some types of geriatric fractures in different parts of the world. The majority of them have dealt with hip fractures, three with forearm injuries and one compared the incidence of hip, distal forearm, proximal humerus and ankle fractures in the four seasons of the year. Of 13 studies in geographic areas located north of 40°latitude, eight showed no seasonal variation in the incidence of fractures, four recorded an increase in the number of fractures in winter and two showed an increased number of fractures in summer. Three of them also studied the effect of daily temperature. Only one study paid attention to biometeorological data and related the biotropic index to the number of injuries treated at the emergency department. Three studies showed that fractures occurred most frequently in the home environment and during the daytime. CONCLUSIONS This study did not prove any statistically significant relationship between the incidence of geriatric fractures and different weather phenomena. Nevertheless, it showed a higher incidence of fractures in winter, from December to February. Most fractures occurred in indoor environments and during the day. A high value of the biotropic index was significantly related to the incidence of geriatric fractures. The most frequent comorbidities included cardiovascular disease, obesity and diabetes mellitus. Key words: geriatric fracture, season, weather, biometeorological forecast.

[Incidence of proximal femur fractures in relation to seasons of the year and weather]. / Distribuce zlomenin horního konce stehenní kosti v závislosti na rocní dobe a pocasí.

PURPOSE OF THE STUDY: The opinion that proximal femur fractures occur mainly in the winter season and are related to slippery surfaces prevails in both the lay and medical communities. The elucidation of this relationship would lead to a better understanding of the aetiology of these fractures and may help to prevent them in the elderly population. MATERIAL AND METHODS: In a retrospective study conducted at two departments, the occurrence of proximal femur fractures in patients 60+ years old in relation to weather conditions (air temperature and its humidity, atmospheric pressure, rain and mist) between January 1, 2001 and December 31, 2005 was investigated. Patients with high-energy or pathological fractures were excluded. The results were evaluated by Statistika software. RESULTS: A total of 1720 patients were studied, of whom 1313 were women and 407 were men. The numbers of fractures did not differ significantly among either the seasons or months of the year. No correlation was found between the number of fractures and each of the weather characteristics (air temperature and its humidity, atmospheric pressure, wind speed and visibility). DISCUSSION: It is widely believed that hip fractures are connected with winter months and temperatures below zero. This is supported by several facts related to winter characteristics, such as slippery icy pavements, clumsiness due to warm bulky clothes, bodies affected by cold and thus predisposed to a fall and poorer visibility on shorter winter days. The effect of seasonal variation on hip fracture incidence has been investigated in 10 studies of which only one has taken the influence of daily temperature into consideration. All studies were conduced in the countries north of 40° latitude, i.e., in climatic conditions similar to our country, with temperatures falling below zero and ice-glazed pavements in winter months. Of them, six have found no relation between proximal femur fractures and weather conditions, two have reported an increased incidence of these fractures in winter months and two in summer months. CONCLUSIONS: Our study did not show any significant relationship between the incidence of proximal femur fractures and weather characteristics. Seasons of the year had no effect on the number of hip fractures or the length of hospital stay due to their treatment.

[Spontaneous symphysis pubis rupture followed by intraabdominal bleeding during the vaginal delivery]. / Spontánní ruptura symfýzy následovaná profúzním krvácením do dutiny brianí behem vaginálního porodu.

Symphysis pubis rupture is rare but life-threatening complication of vaginal delivery. Prompt diagnosis and therapy of this complication is crucial. We present a case report of a patient with a symphysis pubis rupture followed by severe intraabdominal bleeding. The therapy of symphysis pubis rupture is usually conservative according to the available sources. In the case of our patient osteosynthesis was performed with an excellent result.

[Mosaicplasty in the treatment of knee injuries]. / Mozaiková plastika po poranení kolena.

Different types of joint cartilage defects of knee are reported and their surgical treatment indications are given. Types of possible surgical procedures are discussed with detailed description of technique called mosaicplasty--osteochondral autograft transplantation.

[Expense analysis of the proximal femoral fractures treatment]. / Rozbor náikladu na lécbu zlomenin horního konce stehenní kosti.

The aim of this paper was to provide estimated average costs of the hip fractures in the national scale by means of the analysis of the treatment expenses of 256 injured patients who were operated in the 1st Surgical Clinic of the General Teaching Hospital in Prague in 2002. Particular cost items as operation costs, price of the implant, hospitalization expenses by the categories and price of blood derivates were figured out. The follow-up treatment after hospital discharge like price per bed, expenses for general practicioner etc. was considered as well. Each patient was observed for the period of one year after the operation. As a result we came to the total sum of 120,000 Kc per one patient per year. The way to reduce hip fractures treatment cost does not certainly lead to deterioration of medical care quality but to proper treatment of osteoporosis which is the principal cause of these injuries.

[Acute phase reaction in severe injuries]. / Reakce akutní fáze u tezkých úrazu.

UNLABELLED: This study observes acute phase response in first time after injury. HYPOTHESIS: Injured patients are already in first timepiece up severe injury in worse general state developed acute phase response than control group before planed surgery. Levels of indicators acute phase response and haemostasis from venous blood samples collected in an injury day and at patients control group before planned surgery were compared. We compare findings of traumatized in admission day and of patients at 6th-7th day after planned surgery, when is the biggest handicap. Plasma levels of orosomukoid, C reactive protein, prealbumin, transferin, alpha-2-macroglobulin, PAI-1, tPA, sE-Selectin, SICAM, sP-Selectin, antithrombin III, fibrinogen, haemoglobin, time of Quick test, TT, APTT, number of leukocytes, erythrocytes and thrombocytes were determined. RESULTS: Tested group severe injured admitted in I. Surgical Department of First Medical School of Charles University and General Faculty Hospital in Prague in years 1995-1998 (n = 105) be characterized by average value ISS--19.182 +/- 3.315, PTS--28.284 +/- 2.362, AIS--6.739 +/- 0.829 and GCS--11.449 +/- 0.974 and average age 56.89 +/- 4.84 year. Average time hospitalization was 70 days. Between 7th-21st day of hospitalization 23 patients dead on multiorgan failure or sepsis. Control patient file before planned surgery (n = 50) and after planned surgery (n = 33) was comparable in age characteristics. CONCLUSIONS: Adaptation reserve of injured is already in first time-piece since injury significantly lower to patients without trauma. Starting position traumatized patients before acute surgery is comparable with state of patients at 6th-7th day after planned surgery, when culminates postoperative acute phase response.

[Prevention of thromboembolism in surgery of fractures of the upper end of the femur]. / Prevence tromboembolické nemoci u operací pro zlomeninu horního konce stehenní kosti.

Morbidity and mortality after hip fractures is often a result of deep vein thrombosis and pulmonary embolism. Therefore, prophylaxis for venous thrombosis is recommended in patients undergoing osteosynthesis of upper end of lower extremity or arthroplasty of the hip. Study compared efficacy of UFH and LMWH in prevention of thromboembolic disease. The most important part of the study is the prospective trial, which describe group of 81 patients, undergoing operation for hip fracture. These patients suffered fracture of the neck of femur (35) or intertrochanteric fracture (46). For prevention of DVT was used UFH or LMWH. The evaluation was exercised by laboratory tests, Doppler test and by phlebography in cases, where was suspicion of phlebothrombosis. All patients were controlled for two months after operation. Died eleven patients; in every case was PE or cause of death or main complication. Nine of dead was operated for pertrochanteric fracture, another two for fracture of the neck. Prevention drug was UFH in nine dead patients; eight of them suffered pertrochanteric fracture. The most often death sated in fourth and fifth weeks after operation. It means, that the risk of PE continue for a several weeks. It appears, that the prevention use of UFH is not sufficient.

[Metabolic changes caused by artificial ischemia in knee arthroscopy]. / Metabolické zmeny vyvolané arteficiální bezkrevností pri artroskopii kolene.

The most important complication of arthroscopy of the knee is DVT. We studied 53 patients who undergoing arthroscopy with artificial ischemia of lower limb. We examined some biochemics and haematological dates, for example lactate, APTT, INR, PAI-1 etc. In our collection we did not find any case of thromboembolic disease. It seems, that arthroscopy operation with artificial ischemia of lower limb do not increase the risks of DVT. We means, that especially in cases with longer tourniquet time (more than 30 min) is better, when we give some type of Heparin (best is LMWH) as prevention of DVT, because in laboratory results we found significant increase of PAI-1. It is possible, that it can be caused by the rising thrombus.

[Antibiotic prophylaxis in hip joint surgery]. / Antibiotická profylaxe operací kycelního kloubu.

Nosocomial deep wound infections are serious complications after hip joint surgery. Our aim was to determine whether there is a difference in rates of nosocomial infections between group of patients after elective surgery of hip replacement and group of patients with hip replacement after trauma. Both groups of patients had perioperative prophylaxis with amoxycillin. We found that the overall trauma patients infection rate was 0.9 per cent compared with 1.5 per cent for elective surgery infections. In both groups of patients a postsurgery stress was documented according to increase of acute phase proteins (C-reactive protein, orosomucoid and fibrinogen) in plasma for a minimum 10 days after surgery. We conclude, that both groups of patients had benefit from amoxycillin prophylaxis therapy.

[Evaluation of the effect of plastic casts from the aspect of prevention of thromboembolic disease]. / Zhodnocení efektu plastových obvazu z hlediska prevence tromboembolické nemoci.

Immobilization after trauma escalates risk of thrombosis. Our objective was to determine whether there is a difference in rates of deep vein thrombosis (DVT) after immobilization with plastic casts or routinely plaster of Paris in trauma patients. Despite both groups of patients do not show difference in blood coagulation tests (APTT, TT, PT, levels of fibrinogen and of D-dimer in plasma) during time of immobilization the evidence of DVT according to scintigraphy was lower in group of patients with plastic casts (3 per cent to 10 per cent).

[Fatal pulmonary embolisms in surgery patients]. / Smrtelná plicní embólie u chirurgických pacientu.

The authors present results of the study of the fatal pulmonary postoperative embolism in the years 1995-1997. The maximum attention is given to the risk-factors and type of prevention. Among the biggest risks they are malignancy, reduction of pulmonary parenchyma, ischaemic coronary disease, high age and obesity. Risk factors are described in the relation to basic disease. Further the time factors of the pulmonary embolization and the failure or mistakes of prevention are studied. The postoperative long-term risk of the thromboembolism is confirmed.

Increase of soluble cytoadhesive molecules sE-selectin and sICAM-1 and hyperfibrinogenaemia in patients with polytrauma without septicaemia.

Multiple organ failure with thrombophilia is suggested to occur in the course of polytrauma with septicaemia. The aim of the study was to investigate fibrinogen level, other proteins of acute phase response: positive-orosomucoid and negative-transferrin and soluble cytoadhesive molecules in plasma of patients (n = 28) with polytrauma (I-II. stage according to Hannover score) without detectable bacteraemia until 36 hours post injury. The patients treated by massive blood transfusion were excluded. An increase of fibrinogen (Fbg pts 4.34 +/- 2.5 g/l versus control 2.55 +/- 0.55 g/l, p < 0.01), orosomucoid (ORM pts 1.47 +/- 0.8 g/l versus control 0.54 +/- 0.18 g/l, p < 0.01), SE-selectin (sE-sel. pts 92.11 +/- 79.4 g/l versus control 46.6 +/- 29.6 g/l, p < 0.05), sICAM-1 (sICAM pts. 698.3 +/- 54.4 versus control 255.6 +/- 58.0 g/l, p < 0.01) and a decrease of transferrin (Trf pts. 1.77 +/- 0.82 versus control 2.83 +/- 0.71 g/l, p < 0.01) were observed in this patients with polytrauma. We suppose that an increase of fibrinogen and cytoadhesive molecules sE-selectin and sICAM-1 may be induced in patients with polytrauma due to a "non-septic" inflammatory acute phase response in the course of wound healing process after tissue injury too.

[Changes in the distal end of the radius from the aspect of the injured person]. / Zlomeniny distálního konce rádia z hlediska zranených.

Based on an evaluation of a group of patients treated on account of fractures of the wrist. Colles type, we assume that the decisive factor is the type of fracture. We recommend therefore to divide these fractures into two groups. The first one includes all types where the fracture line does not involve the radiocarpal or radioulnar joint. The second one includes all multifragmental intraarticular fractures where an active surgical procedure can improve hitherto achieved therapeutic results.

[Injuries of the ligaments of the talar joint]. / Poranení vazu hlezenného kloubu.

Based on experience with the treatment of 404 patients with injuries of the soft parts of the talus the authors maintain that markedly better results are achieved in patients where sufficiently long immobilization with a plaster bandage was used or where early reconstruction of the injured ligaments was performed. A very important negative factor is treatment of these injuries without immobilization or inadequate immobilization, as a high percentage of the patients develop instability of the talus with all its consequences. The authors consider arthrography the exact diagnostic method, the results of which are decisive for the therapeutic procedure.

Chalone-like inhibition of DNA synthesis in helminths.

Chalone-like inhibitory activity was found in extracts from tissues of Taenia crassiceps cysticercus and tissues of adult Ascaris suum. The inhibitory effects were partially species nonspecific: The extracts from T. crassiceps larvae inhibit both T. crassiceps and Mesocestoides corti larvae DNA synthesis. Extracts from A. suum, however, inhibit only T. crassiceps. Besides them, the inhibitory factor from mouse brain inhibits both T. crassiceps and M. corti DNA synthesis. When the inhibitory factor from A. suum was applied 4 times during 24-hr culture (at 6-hr intervals), the inhibitory effect was decreased.

E rosettes in the uranium miners with lung cancer.

Rosette forming cells (RFC) were evaluated in the peripheral blood of healthy persons, patients with lung cancer and chronic bronchitis. Simultaneously the levels of RFC in persons with and without radiation exposure were compared. Two types of rosettes were enumerated: 1) lymphocytes binding 1 or 2 sheep red blood cells (SRBC), 2) lymphocytes binding 3 or more SRBC. Then the sum of both types was calculated. The patients with lung cancer were divided according to the TNM classification and histological types. The relative and absolute numbers of RFC in 1 microliter of peripheral blood proved depressed capacity of peripheral T-lymphocytes to form rosettes not only in patients with cancer or chronic bronchitis but also in controls with radiation exposure. Furthermore, there was established that the control group with radiation exposure was not different from the patients with cancer or chronic bronchitis.