Low-molecular-weight heparins in the treatment of deep-vein thrombosis

OBJECTIVE: To compare the characteristics and clinical efficacy of low-molecular-weight heparins (LMWHs) and unfractionated heparin (UFH) in the treatment of deep-vein thrombosis (DVT). Adverse effects, dosing, and cost issues are also discussed. DATA SOURCES: A MEDLINE search (January 1984-October 1997) was used to identify pertinent French and English literature, including clinical trials and reviews on LMWHs and their use in DVT. STUDY SELECTION: Trials comparing dalteparin, enoxaparin, tinzaparin, and nadroparin with UFH were selected. As studies were numerous, only randomized trials including more than 50 patients were reviewed. Moreover, all patients studied had a first episode of symptomatic DVT confirmed by objective tests (i.e., venography, duplex ultrasonography, impedance plethysmography). Clinical efficacy and safety of LMWHs were assessed in these trials. DATA EXTRACTION: Results pertaining to venographic assessment, recurrent thromboembolism, total mortality, and bleeding complications were extracted from the selected studies. DATA SYNTHESIS: Compared with UFH, LMWHs have a longer plasma half-life, better subcutaneous bioavailability, more predictable anticoagulant response, and require less intense laboratory monitoring. Most trials demonstrate comparable effects on thrombus extension and incidence of recurrent thromboembolism. Compared with UFH, LMWHs do not alter total mortality. Although animal trials predict a lower hemorrhagic potential for LMWHs, the incidence of bleeding complications is generally similar to that observed with UFH. Outpatient management of DVT with LMWHs has shown comparable safety and efficacy with inpatient UFH use but a shorter hospital stay. CONCLUSIONS: Because LMWHs are as safe and as effective as UFH, and because of their more convenient method of administration, they can be considered valuable alternatives for the treatment of DVT. Savings generated by less intensive laboratory monitoring and the possibility of early hospital discharge and outpatient therapy may outweight the higher acquisition cost of LMWHs.     

Danaparoid in the prevention of thromboembolic complications

OBJECTIVE: To review the therapies used to prevent postoperative thromboembolic complications with a focus on the role of danaparoid, a new low-molecular-weight glycosaminoglycan. DATA SOURCES: A MEDLINE search was performed to identify pertinent English-language literature including studies, abstracts, and review articles. Key search terms included danaparoid, heparinoid, lomoparin, heparin, prophylaxis, thrombosis, embolism, thromboembolism, and thromboembolic and postoperative complications. The manufacturer of danaparoid was contracted for additional information related to this compound. STUDY SELECTION AND DATA EXTRACTION: All identified articles were reviewed for possible inclusion in this review. Comparisons primarily focused on data obtained from prospective, randomized, controlled, blind clinical trials. Another important consideration was the use of venography to determine the presence of deep venous thrombosis. DATA SYNTHESIS: Various therapies are available for the prevention of postoperative thromboembolic complications. Effective pharmacologic treatments currently available include adjusted-dose heparin, warfarin, aspirin, dextran, and low-molecular-weight heparins (LMWHs). Until recently, warfarin was considered the drug of choice for thromboprophylaxis in high-risk patients, including patients undergoing orthopedic surgical procedures. Because of their comparable efficacy and greater ease of use, LMWHs are gaining favor over warfarin in this patient population. In well-designed clinical trials involving patients undergoing elective total hip replacement or fractured hip surgery, danaparoid has demonstrated greater efficacy than other active treatments, including warfarin, dextran, aspirin, and heparin plus dihydroergotamine. While studies comparing danaparoid with LMWHs have not yet been published, danaparoid may be more useful in patients with heparin-associated thrombocytopenia. CONCLUSIONS: Danaparoid is an antithrombotic agent with characteristics that distinguish it from heparin and LMWHs. Based on the efficacy and safety data reviewed, danaparoid should be considered one of the drugs of choice for the prevention of thromboembolic complications in patients undergoing orthopedic hip procedures and the drug of choice for the management of any patient with heparin-induced thrombocytopenia who requires anticoagulant therapy.     

Risk factors and prevention of thromboembolic risk in laparoscopy

PURPOSE: To investigate if retinol and carotenoids are present in the subretinal space following rhegmatogenous retinal detachment. METHODS: Blood and subretinal fluid were collected from patients at the time of surgical repair of retinal detachment. After removal of cellular contents in a specimen by centrifugation, the supernatant fraction was analyzed by liquid chromatography using a silica column eluted by 16% dioxane in hexane. Retinol and carotenoids were identified in the chromatograms based on their retention time and absorption spectrum. RESULTS: The retinol concentrations (mean+/-SD) in the serum and subretinal fluid were 305+/-144 and 166+/-96 ng/ml respectively. The 450 nm chromatogram had 7 peaks with the characteristic absorption spectrum of carotenoids. Peak 1 and 7 coincided with the retention time of beta-carotene (1.8 min) and lutein (10.8 min) respectively. The concentrations of beta-carotene and lutein in serum were 161+/-63 and 142+/-98 ng/ml respectively. There was very little beta-carotene in subretinal fluid (4.7+/-2.4 ng/ml). Lutein was the major carotenoid peak in subretinal fluid (41.4+/-14.1 ng/ml). The minor carotenoid peaks of serum were not observed in subretinal fluid. CONCLUSION: There is a substantial amount of retinol and lutein in subretinal fluid. The high proportion of lutein and very low amount of beta-carotene in the subretinal fluid support the occurrence of a highly selection transport mechanism of lutein from the blood to the retina.     

The role of Lactobacillus acidophilus in the prevention and adjuvant therapy of certain infectious diseases

Authors call attention to the role of lactic acid bacteria in the prevention and adjuvant therapy of certain infective diseases. It has special importance in the prevention and adjuvant therapy of new-born and childhood enteritis, different urogenital inflammations and antibiotic associated diarrhoea. Administration of lactic acid bacteria create eubiosis between the human organism and the world of bacteria, that is, eubacteriosis is developed instead of a pathogen flora, assuring normal physiologic functions for the well-being of the organism.     

Vitamin E in therapy of rheumatic diseases]

Methyl t-butyl ether (MTBE) and ethyl t-butyl ether (ETBE) are commonly used in unleaded gasoline to increase the oxygen content of fuel and to reduce carbon monoxide emissions from motor vehicles. This study was undertaken to investigate: (1) the effect of administration to rats of ETBE and its metabolite, t-butanol, on the induction and/or inhibition of hepatic P450 isoenzymes; (2) the oxidative metabolism of MTBE and ETBE by liver microsomes from rats pretreated with selected P450 inducers and purified rat P450(s), (2B1, 2E1, 2C11, 1A1). ETBE administration by gavage at a dose of 2 ml/kg for 2 days induced hepatic microsomal P4502E1-linked p-nitrophenol hydroxylase and the P4502B1/2-associated PROD and 16beta-testosterone hydroxylase, verified by immunoblot experiments. t-Butanol treatments at doses of 200 and 400 mg/kg i.p. for 4 days did not alter any liver microsomal monoxygenases. Both MTBE and ETBE were substrates for rat liver microsomes and were oxidatively dealkylated to yield formaldehyde and acetaldehyde, respectively. The dealkylation rates of both MTBE and ETBE were increased c. fourfold in phenobarbital (PB)-treated rats. In rats pretreated with pyrazole, an inducer of 2E1, only the demethylation of MTBE was increased (c. twofold). When the oxidations of MTBE and ETBE were investigated with purified P450(s) in a reconstituted system, it was found that P4502B1 had the highest activities towards both solvents, whereas 1A1 and 2C1 were only slightly active; P4502E1 had an appreciable activity on MTBE but not against ETBE. Metyrapone, a potent inhibitor of P450 2B, consistently inhibited both the MTBE and ETBE dealkylations in microsomes from PB-treated rats. Furthermore, 4-methylpyrazole (a probe inhibitor of 2E1) and anti-P4502E1 IgG showed inhibition, though modest, only on MTBE demethylation, but not on ETBE deethylation. Inhibition experiments have also suggested that rat 2A1 may exert an important role in MTBE and ETBE oxidation. Taken together, these results indicate that 2B1, when expressed, is the major enzyme involved in the oxidation of these two solvents and that 2E1 may have a role, although minor, in MTBE demethylation. The implications of these data for MTBE and ETBE toxicity remain to be established.     

Immunomodulators in the prevention and therapy of viral infections]

Three-dimensional (3-D) reconstruction methods were employed to study the anatomy of the vestibular aqueducts (VAs) in ten postmortem temporal bone specimens obtained from ten individuals aged 4 months to 70 years at death. After reconstruction, the ten 3-D images of VAs were superimposed on one another and differences evaluated. The VA showed postnatal growth and variations in size and shape. However, the variations in angle at which the VA bends near the isthmus were not correlated with age. Furthermore, study of the superimposed images revealed that the 3-D course of the VA was essentially the same in individuals of all ages, despite its wide variability in size and shape. These results indicate that the basic course of the VA is determined before early infancy although the VA grows thereafter, suggesting that VA anomalies such as "large vestibular aqueduct syndrome" (in which the VA takes an abnormally straight and wide course) may be established prenatally.     

Low-molecular-weight heparin in the prevention of thromboembolism in pregnant thrombophilic patients

The usual small apical pneumothorax has been previously described as being typified on chest radiographs by a pencil-thin white line that represents the retracted visceral pleura. Occasionally the apical visceral pleura can become thickened, known as the apical cap, which leads to a variant presentation of apical pneumothorax. To our knowledge, this variant presentation has never been described in the literature, and should improve the detection of apical pneumothorax.     

Nutrition in the pathogenesis, therapy and prevention of digestive system diseases

The role of nutrition in the pathogenesis, therapy, and prevention of gastrointestinal diseases is discussed. Although nutrition is not a leading cause of most gastrointestinal diseases, the role of nutrition in their pathogenesis is very great. Nutritional monitoring of the Russian Federation's population has revealed a shortage of many essential nutrients to be consumed, which may result in worsening of various gastrointestinal diseases. The most promising way of solving this problem is to supplement their diets with biologically active additives (Nutricevtics) which may be a main source of essential nutrients, such as vitamins B, beta-carotene and omega 3-polyunsaturated fatty acids.     

Anticoagulant therapy of thromboembolic disease during pregnancy

There is growing interest in low molecular weight heparin for the management of thromboembolic disease in pregnancy. Greater understanding of the risk of thromboembolic disease versus the risk of various management practices is urgently needed to reduce maternal mortality and embryopathy in the fetus.     

The chronopharmacotherapy of diseases]

Peroperative cholangiography (POC) performed as a routine during cholecystectomy for cholelithiasis was evaluated in 102 patients. POC was normal 93 patients. Nine patients had abnormal POCs: 5 were true positive--CBD stones (4) and sphincteric fibrosis (1): 4 were false positive--air bubbles (2) and sphincteric spasm (2). Preoperative indication of CBD stones were present in 12 patients-5 of these had abnormal POC (4 true positive and 1 false positive). CBD exploration was avoided in 7 patients with normal POC. Ninety patients did not have any preoperative indication of CBD stones-4 of these had abnormal POC (1 true positive and 3 false positive). None of the patients with a normal POC had any clinical evidence of residual stones on follow up for one year. POC did not help in any case to delineate biliary ductal anatomy. Routine POC during cholecystectomy should be abandoned and should be performed selectively in patients suspected to have CBD stones only to avoid a negative CBD exploration.     

Efficacy of prevention of thromboembolic complications with LMW-heparin in experiment

The authors used an antithrombotic agent (Nadroparin Calcium) with anti-Xa effect in their experiments to prevent thromboembolic complications in the model of endoprosthetic replacement of the hip joint in mongrel dogs. 10 experimental animals (Group I.) were given doses of 100 A Xa ICU/kg/bwt of Nadroparin Calcium subcutaneously 4 hours prior to the operation and also once a day until the 3rd postoperative day; between the 4th and 10th postoperative days doses of 150 A Xa ICU/kg/bwt Nadroparin Calcium were given. The 10 control animals (Group II.) did not receive anticoagulant treatment. In both groups platelet count, activated partial thromboplastin times (APTT), prothrombin and fibrinogen levels as well as activated factor X inhibition (F Xa) were measured prior to surgery and also until the 14th postoperative day. No changes in APTT and prothrombin levels were detected during the experiment, however platelet count and fibrinogen levels as well as the extent of F Xa inhibition showed significant and different changes in groups I. and II. The Group I. which had received thromboembolic prophylaxis did not develop deep venous thrombosis or pulmonary embolism, but the control group did. Based on their investigations, the authors concluded that they had been able to achieve F Xa inhibition by giving the above mentioned doses of Nadroparin Calcium which was enough to prevent thromboembolic complications in their model experiment of implanting hip endoprosthesis.     

Breast feeding for prevention of viral acute respiratory diseases in infants]

The incidence of acute viral respiratory diseases (confirmed by immunofluorescence test) was compared in a group of 159 infants aged 0-9 months breast-fed at least once daily and in a group of 608 infants of similar age and hospitalization duration receiving only artificial food. The incidence was significantly lower in breast-fed infants (p = 0.00057), especially in the first trimester of life (p = 0.00039). This was valid of all RSV infections (p = 0.01854) and parainfluenza type 4 virus infections (p = 0.0846). The antibody level against parainfluenza type 1 and 3 (HI) and against RSV in IgA class (ELISA) was compared with that in mother's milk and serum. No significant correlation was found for parainfluenza type 1 antibodies (r = 0.159) and 3 (r = 0.025), while for RSV the correlation was positive and statistically significant though rather low (r = 0.234). No significant correlation was found between milk antibody levels and the incidence of acute viral respiratory infections. Breast-feeding showed a significant influence on the lower incidence of these infections, particularly in the first trimester of life. It seems that this was associated with a non-specific mechanism rather than with the milk levels of specific antibodies.     

The postcholecystectomy syndrome and its prevention]

The authors have made an analysis of results of clinical observations of 953 patients with gunshot wounds of soft tissues. It was found that primary surgical treatment (PST) of the gunshot wounds often proved to be not radical. Later it required reoperations in 30% of the wounded. To get more exact indications for a repeated surgical treatment it is necessary to make a careful revision of the gunshot wound within 3-5 days after getting the wound. The indications for reoperations are as follows: the development of secondary necrosis of the tissues necessary removal of the foreign body, opening of the pockets and leaks in order to provide valuable drainage as well as nonradical PST due to various causes. Reoperations performed according to the indications allowed to make the duration of treatment at an average 7 days shorter and the development of suppurations two times less frequent.     

Progress in prevention and therapy of infectious complications in children and adolescents with neoplastic diseases

Due to the high dose-intensity of most current treatment protocols, the growing number of marrow transplantations, the routine use of aggressive supportive care and certain pathogen-related problems, infections remain an important cause for morbidity and mortality in children and adolescents with cancer. Over the last decade, however, considerable progress has been made in diagnosis, prevention and treatment of infectious complications in the immunocompromised host. This article first delineates both clinical approach and current treatment strategies in the pediatric cancer patient presenting with neutropenia and fever of unknown origin. It then reviews diagnosis and treatment of the most common specific infections and concludes with a discussion of preventive measures in the setting of anticancer treatment.