Нозокомиальная пневмония у взрослых: национальные рекомендации

1. Чучалин А.Г., Синопальников А.И., Страчунский Л.С. и др. Нозокомиальная пневмония у взрослых: практические рекомендации по диагностике, лечению и профилактике. Пособие для врачей. Пульмонология 2005; 3: 13-36.

2. Гельфанд Б.Р., Белоцерковский Б.З., Проценко Д.Н. и др. Нозокомиальная пневмония в хирургии. Методические рекомендации. Инфекции и антимикроб. терапия 2003; 5-6: 124-129.

3. Bellomo R., Bagshaw S.M. Evidence-based medicine: classifying the evidence from clinical trials - the need to consider other dimensions. Crit. Care 2006; 10 (5): 232.

4. Hospital-acquired pneumonia in adults: diagnosis, assessment of severity, initial antimicrobial therapy, and preventive strategies. A consensus statement, American Thoracic Society, November 1995. Am. J. Respir. Crit. Care Med. 1996; 153 (5): 1711-1725.

5. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am. J. Respir. Crit. Care Med. 2005; 171 (4): 388-416.

6. Kirtland S.H., Corlev D.E., Winterbauer R.H. et al. The diagnosis of ventilator-associated pneumonia: a comparison of histologic, microbiologic, and clinical criteria. Chest 1997; 112 (2): 445-457.

7. Fagon J.Y., Chastre J., Domart Y. et al. Nosocomial pneumonia in patients receiving continuous mechanical ventilation. Prospective analysis of 52 episodes with use of a protected specimen brush and quantitative culture techniques. Am. Rev. Respir. Dis. 1989; 139 (4): 877-884.

8. Montravers P., Veber B., Aubover C. et al. Diagnostic and therapeutic management of nosocomial pneumonia in surgical patients: results of the Eole study. Crit. Care Med. 2002; 30 (2): 368-375.

9. Rello J., Ausina V., Ricart M. et al. Impact of previous antimicrobial therapy on the etiology and outcome of ventilator-associated pneumonia. Chest 1993; 104 (4): 1230-1235.

10. Trouillet J.L., Chastre J., Vuagnat A. et al. Ventilator-associated pneumonia caused by potentially drug-resistant bacteria. Am. J. Respir. Crit. Care Med. 1998; 157 (2): 531-539.

11. Celis R., Torres A., Gatell J.M. et al. Nosocomial pneumonia. A multivariate analysis of risk and prognosis. Chest 1988; 93 (2): 318-324.

12. Kollef M.H., Silver P., Murphy D.M. et al. The effect of late-on-set ventilator-associated pneumonia in determining patient mortality. Chest 1995; 108 (6): 1655-1662.

13. Bregeon F., Ciais V., Carret V. et al. Is ventilator-associated pneumonia an independent risk factor for death? Anesthesiology 2001; 94 (4): 554-560.

14. Rello J., Sa-Bores M., Correa H. et al. Variations in etiology of ventilator-associated pneumonia across four treatment sites: implications for antimicrobial prescribing practices. Am. J. Respir. Crit. Care Med. 1999; 160 (2): 608-613.

15. Зуева Л.П. Эпидемиологическое наблюдение: принципы организации и методы проведения: Метод. рекомендации. СПб.; 2004.

16. Белобородов В.Б. Современный взгляд на лечение и профилактику инфекций в ОРИТ. М.; 2005.

17. Alberti C., Brun&Buisson C., Burchardi H. et al. Epidemiology of sepsis and infection in ICU patients from an international multicentre cohort study. Intensive Care Med. 2002; 28 (2): 108-121.

18. Климова Г.М., Клюжев В.М., Акимкин В.Г. и др. Эпидемиология и профилактика септических инфекционных осложнений у больных отделений реанимации и интенсивной терапии хирургического профиля. Эпи демиол. и вакцинопрофилакт. 2006; 3 (28): 33-37.

19. Gastmeier P., Geffers C., Sohr D. et al. Five years working with the German nosocomial infection surveillance system (Krankenhaus Infections Surveillance System). Am. J. Infect. Control 2003; 31 (5): 316-321.

20. Morehead R.S., Pinto S.J. Ventilator-associated pneumonia. Arch. Intern. Med. 2000; 160 (13): 1926-1936.

21. Ricard J., C.G., Boucherie M., Conti G. et al. VAPWAY project: A European audit of VAP prevention practices. Intens. Care Med. 2008; 34 (suppl. 1): S 36.

22. Dodek P., Keenan S., Cook D. et al. Evidence-based clinical practice guideline for the prevention of ventilator-associated pneumonia. Ann. Intern. Med. 2004; 141 (4): 305-313.

23. Richards M.J., Edwards J.R., Culver D.H. et al. Nosocomial infections in combined medical-surgical intensive care units in the United States. Infect. Control. Hosp. Epidemiol. 2000; 21 (8): 510-515.

24. Vincent J.L., Bihari D.J., Suter P.M. et al. The prevalence of nosocomial infection in intensive care units in Europe. Results of the European Prevalence of Infection in Intensive Care (EPIC) Study. EPIC International Advisory Committee. J. A. M. A. 1995; 274 (8): 639-644.

25. Vincent J.L., European Prevalence of Infection in Intensive Care. EPIC II study. 28th ISICEM; 2008.

26. Baker A.M., Meredith J.W., Haponik E.F. Pneumonia in intubated trauma patients. Microbiology and outcomes. Am. J. Respir. Crit. Care Med. 1996; 153 (1): 343-349.

27. Craig C.P., Conelly S. Effect of intensive care unit nosocomial pneumonia on duration of stay and mortality. Am. J. Infect. Control. 1984; 12 (4): 233-238.

28. Cunnion K.M., Weber D.J., Broadhead W.E. et al. Risk factors for nosocomial pneumonia: comparing adult critical care populations. Am. J. Respir. Crit. Care Med. 1996; 153 (1): 158-162.

29. Cook D.J., Kollef M.H. Risk factors for ICU-acquired pneumonia. J. A. M. A. 1998; 279 (20): 1605-1606.

30. Soo Hoo G.W., Wen E., Nguyen T.V. et al. Impact of clinical guidelines in the management of severe hospital-acquired pneumonia. Chest 2005; 128 (4): 2778-2787.

31. Craven D.E. Epidemiology of ventilator-associated pneumonia. Chest 2000; 117 (4, suppl. 2): 186S-187S.

32. Craven D.E., Steger K.A. Epidemiology of nosocomial pneumonia. New perspectives on an old disease. Chest 1995; 108 (2, suppl.): 1S-16S.

33. Papazian L., Bregeon F., Thirion X. et al. Effect of ventilator-associated pneumonia on mortality and morbidity. Am. J. Respir. Crit. Care Med. 1996; 154 (1): 91-97.

34. Heyland D.K., Cook D.J., Grifith L. et al. The attributable morbidity and mortality of ventilatorassociated pneumonia in the critically ill patient. The Canadian Critical Trials Group. Am. J. Respir. Crit. Care Med. 1999; 159 (4, pt. 1): 1249-1256.

35. Bercault N., Boulain T. Mortality rate attributable to ventilator-associated nosocomial pneumonia in an adult intensive care unit: a prospective case-control study. Crit. Care Med. 2001; 29 (12): 2303-2309.

36. Rello J., Lorente C., Bodi M. et al. Why do physicians not follow evidence-based guidelines for preventing ventilator-associated pneumonia: a survey based on the opinions of an international panel of intensivists. Chest 2002; 122 (2): 656-661.

37. Нозокомиальная пневмония, связанная с искусственной вентиляцией легких (НПивл), у хирургических больных. / Гельфанд Б.Р., Гологорский В.А., Белоцерковский Б.З. и др. М.; 2000.

38. Hunter J., Annadurai S., Rothwell M. Diagnosis, management and prevention of ventilatorassociated pneumonia in the UK. Eur. J. Anaesthesiol. 2007; 24 (11): 971-977.

39. Kollef M.H. The prevention of ventilator-associated pneumonia. N. Engl. J. Med. 1999. 340 (8): 627-634.

40. Shorr A.F., Kollef M.H. Ventilator-associated pneumonia: insights from recent clinical trials. Chest 2005; 128 (5, suppl. 2): 583S-591S.

41. Chastre J., Fagon J.Y. Ventilator-associated pneumonia. Am. J. Respir. Crit. Care Med. 2002; 165 (7): 867-903.

42. A randomized trial of diagnostic techniques for ventilator-associated pneumonia. N. Engl. J. Med. 2006; 355 (25): 2619-2630.

43. Chinsky K.D. Ventilator-associated pneumonia: is there any gold in these standards? Chest 2002; 122 (6): 1883-1885.

44. Fagon J.Y., Chastre J., Hance A.J. et al. Nosocomial pneumonia in ventilated patients: a cohort study evaluating attributable mortality and hospital stay. Am. J. Med. 1993; 94 (3): 281-288.

45. Masterton R.G., Galloway A., French G. et al. Guidelines for the management of hospital acquired pneumonia in the UK: report of the working party on hospital-acquired pneumonia of the British Society for Antimicrobial Chemotherapy. J. Antimicrob. Chemother. 2008; 62 (1): 5-34.

46. Public health focus: surveillance, prevention, and control of nosocomial infections. Morbid. Mortal Wkly Rep. 1992; 41 (42): 783-787.

47. Torres A., Ewig S., Lode H. et al. Defining, treating and preventing hospital acquired pneumonia: European perspective. Intensive Care Med. 2009; 35 (1): 9-29.

48. Sirvent J.M., Torres A., Vidour L. et al. Tracheal colonisation within 24 h of intubation in patients with head trauma: risk factor for developing early-onset ventilator-associated pneumonia. Intensive Care Med. 2000; 26 (9): 1369-1372.

49. Drakulovic M.B., Torres A., Bauer T. et al. Supine body position as a risk factor for nosocomial pneumonia in mechanically ventilated patients: a randomised trial. Lancet 1999; 354 (9193): 1851-1858.

50. Ibrahim E.H., Mehringer L., Prentice D. et al. Early versus late enteral feeding of mechanically ventilated patients: results of a clinical trial. J. Parenter. Enteral. Nutr. 2002; 26 (3): 174-181.

51. Craven D.E., Driks M.R. Nosocomial pneumonia in the intubated patient. Semin. Respir. Infect. 1987; 2 (1): 20-33.

52. Craven D.E., Kunches L.M., Kilinsky V. et al. Risk factors for pneumonia and fatality in patients receiving continuous mechanical ventilation. Am. Rev. Respir. Dis. 1986; 133 (5): 792-796.

53. Winterbauer R.H., Durning R.B., Barron E. et al. Aspirated nasogastric feeding solution detected by glucose strips. Ann. Intern. Med. 1981; 95 (1): 67-68.

54. Holzapfel L., Chervet S., Madinier G. et al. Influence of long-term oro- or nasotracheal intubation on nosocomial maxillary sinusitis and pneumonia: results of a prospective, randomized, clinical trial. Crit. Care Med. 1993; 21 (8): 1132-1138.

55. Adair C.G., Gorman S.P., Feron B.M. et al. Implications of endotracheal tube biofilm for ventilator-associated pneu monia. Intensive Care Med. 1999; 25 (10): 1072-1076.

56. Pingleton S.K., Hinthorn D.R., Liu C. Enteral nutrition in patients receiving mechanical ventilation. Multiple sources of tracheal colonization include the stomach. Am. J. Med. 1986; 80 (5): 827-832.

57. Torres A., Serra&Batlles J., Ros E. et al. Pulmonary aspiration of gastric contents in patients receiving mechanical ventilation: the effect of body position. Ann. Intern. Med. 1992; 116 (7): 540-543.

58. Pugin J., Auckenthaler R., Mili N. et al. Diagnosis of ventilator-associated pneumonia by bacteriologic analysis of bronchoscopic and nonbronchoscopic "blind" bronchoalveolar lavage fluid. Am. Rev. Respir. Dis. 1991; 143 (5, pt. 1): 1121-1129.

59. Luna C.M., Balnzaco D., Niederman M.S. et al. Resolution of ventilator-associated pneumonia: prospective evaluation of the clinical pulmonary infection score as an early clinical predictor of outcome. Crit. Care Med. 2003; 31 (3): 676-682.

60. Chastre J., Wolff M., Fagon J.Y. et al. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. J. A. M. A. 2003; 290 (19): 2588-2598.

61. Samama M.M., Cohen A.T., Darmon J.Y. et al. A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. Prophylaxis in Medical Patients with Enoxaparin Study Group. N. Engl. J. Med. 1999; 341 (11): 793-800.

62. Geerts W., Selby R. Prevention of venous thromboembolism in the ICU. Chest 2003; 124 (6, suppl.): 357S- 363S.

63. Attia J., Rav J.G., Cook D.J. et al. Deep vein thrombosis and its prevention in critically ill adults. Arch. Intern. Med. 2001; 161 (10): 1268-1279.

64. Colwell C.W. Jr. Recent advances in the use of low molecular weight heparins as prophylaxis for deep vein thrombosis. Orthopedics 1994; 17 (suppl.): 5-7.

65. Geerts W.H., Jay R.M., Code K.I. et al. A comparison of low-dose heparin with low-molecularweight heparin as prophylaxis against venous thromboembolism after major trauma. N. Engl. J. Med. 1996; 335 (10): 701-707.

66. Vanek V.W. Meta-analysis of effectiveness of intermittent pneumatic compression devices with a comparison of thigh-high to knee-high sleeves. Am. Surg. 1998; 64 (11): 1050-1058.

67. Hamilton G., Baker D. Graduated compression stockings in the prevention of venous thromboembolism. Br. J. Surg. 1999; 86 (8): 992-1004.

68. Cook D.J., Witt L.G., Cook R.J. et al. Stress ulcer prophylaxis in the critically ill: a meta-analysis. Am. J. Med. 1991; 91 (5): 519-527.

69. Levy M.J., Seelig C.D., Robinson N.J. et al. Comparison of omeprazole and ranitidine for stress ulcer prophylaxis. Dig. Dis. Sci. 1997; 42 (6): 1255-1259.

70. Conrad S.A., Gabrielli A., Margolis B. et al. Randomized, doubleblind comparison of immediate-release omeprazole oral suspension versus intravenous cimetidine for the prevention of upper gastrointestinal bleeding in critically ill patients. Crit. Care Med. 2005; 33 (4): 760-765.

71. Kahn J.M., Doctor J.N., Rubenfeld G.D. Stress ulcer prophylaxis in mechanically ventilated patients: integrating evidence and judgment using a decision analysis. Intensive Care Med. 2006; 32 (8): 1151-1158.

72. Turgeon A.F., Hutton B., Fergusson D.A. et al. Meta-analysis: intravenous immunoglobulin in critically ill adult patients with sepsis. Ann. Intern. Med. 2007; 146 (3): 193-203.

73. Laupland K.B., Kirkpatrick A.W., Delaney D. Polyclonal intravenous immunoglobulin for the treatment of severe sepsis and septic shock in critically ill adults: A systematic review and meta-analysis. Crit. Care Med. 2007; 35 (12): 2686-2692.

74. Kreymann K.G., de Heer G., Nierhaus A. et al. Use of polyclonal immunoglobulins as adjunctive therapy for sepsis or septic shock. Crit. Care Med. 2007; 35 (12): 2677-2685.

75. Colin G., Annane D. Corticosteroids and human recombinant activated protein C for septic shock. Clin. Chest. Med. 2008; 29 (4): 705-712.

76. Patterson T.F., Patterson J.E., Masecar B.L. et al. A nosocomial outbreak of Branhamella catarrhalis confirmed by restriction endonuclease analysis. J. Infect. Dis. 1988; 157 (5): 996-1001.

77. Brochard L., Mancebo J., Wysocki M. et al. Noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease. N. Engl. J. Med. 1995; 333 (13): 817-822.

78. Ferrer M., Esquinas A., Leon M. et al. Noninvasive ventilation in severe hypoxemic respiratory failure: a randomized clinical trial. Am. J. Respir. Crit. Care Med. 2003; 168 (12): 1438-1444.

79. Confalonieri M., Corini M., Ambrosino N. et al. Respiratory intensive care units in Italy: a national census and prospective cohort study. Thorax 2001; 56 (5): 373-378.

80. Ferrer M., Esquinas A., Arancibia F. et al. Noninvasive ventilation during persistent weaning failure: a randomized controlled trial. Am. J. Respir. Crit. Care Med. 2003; 168 (1): 70-76.

81. Antonelli M., Conti G., Moro M.L. et al. Predictors of failure of noninvasive positive pressure ventilation in patients with acute hypoxemic respiratory failure: a multicenter study. Intensive Care Med. 2001; 27 (11): 1718-1728.

82. Wheeler A.P., Carroll F.E., Bernard G.R. Radiographic issues in adult respiratory distress syndrome. New Horiz. 1993; 1 (4): 471-477.

83. Malbouisson L.M., Busch C.J., Puybasset L. et al. Role of the heart in the loss of aeration characterizing lower lobes in acute respiratory distress syndrome. CT Scan ARDS Study Group. Am. J. Respir. Crit. Care Med. 2000; 161 (6): 2005-2012.

84. Malbouisson L.M., Muller J.C., Constantin J.M. et al. Computed tomography assessment of positive end-expiratory pressure-induced alveolar recruitment in patients with acute respiratory distress syndrome. Am. J. Respir. Crit. Care Med. 2001; 163 (6): 1444-1450.

85. Mancebo J. Permissive hypercapnia in ARDS. Intensive Care Med. 1998; 24 (12): 1339-1340.

86. Lodato R.F. Oxygen toxicity. Crit. Care Clin. 1990; 6 (3): 749-765.

87. Amato M.B., Barbas C.S., Medeiros D.M. et al. Beneficial effects of the "open lung approach" with low distending pressures in acute respiratory distress syndrome. A prospective randomized study on mechanical ventilation. Am. J. Respir. Crit. Care Med. 1995; 152 (6, pt. 1): 1835-1846.

88. Mancebo J., Amaro P., Mollo J.L. et al. Comparison of the effects of pressure support ventilation delivered by three different ventilators during weaning from mechanical ventilation. Intensive Care Med. 1995; 21 (11): 913-919.

89. Brochard L., Roudot-Thoraval F., Roupie E. et al. Tidal volume reduction for prevention of ventilator-induced lung injury in acute respiratory distress syndrome. The Multicenter Trail Group on Tidal Volume reduction in ARDS. Am. J. Respir. Crit. Care Med. 1998; 158 (6): 1831-1838.

90. Ranieri V.M., Mascia L., Fiore T. et al. Cardiorespiratory effects of positive end-expiratory pressure during progressive tidal volume reduction (permissive hypercapnia) in patients with acute respiratory distress syndrome. Anesthesiology 1995; 83 (4): 710-720.

91. Eichacker P.Q., Gerstenberger E.P., Banks S.M. et al. Meta-analysis of acute lung injury and acute respiratory distress syndrome trials testing low tidal volumes. Am. J. Respir. Crit. Care Med. 2002; 166 (11): 1510-1514.

92. Jonson B., Richard J.C., Straus C. et al. Pressure-volume curves and compliance in acute lung injury: evidence of recruitment above the lower inflection point. Am. J. Respir. Crit. Care Med. 1999; 159 (4, pt. 1): 1172-1178.

93. Lu Q., Malbouisson L.M., Mourgeon E. et al. Assessment of PEEP-induced reopening of collapsed lung regions in acute lung injury: are one or three CT sections representative of the entire lung? Intensive Care Med. 2001; 27 (9): 1504-1510.

94. Dreyfuss D., Saumon G. Ventilator-induced lung injury: lessons from experimental studies. Am. J. Respir. Crit. Care Med. 1998; 157 (1): 294-323.

95. Протокол ведения больных, диагностика и интенсивная терапия СОПЛ и ОРДС: Методические рекомендации Федерации анестезиологов-реаниматологов РФ. М.; 2006.

96. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N. Engl. J. Med. 2000; 342 (18): 1301-1308.

97. Bone R.C. The ARDS lung. New insights from computed tomography. J. A. M. A. 1993; 269 (16): 2134-2135.

98. Ward N.S. Effects of prone position ventilation in ARDS. An evidence-based review of the literature. Crit. Care Clin. 2002; 18 (1): 35-44.

99. Stiller K. Physiotherapy in intensive care: towards an evidence-based practice. Chest 2000; 118 (6): 1801-1813.

100. Graham W.G., Bradley D.A. Efficacy of chest physiotherapy and intermittent positive-pressure breathing in the resolution of pneumonia. N. Engl. J. Med. 1978; 299 (12): 624-627.

101. Kirilloff L.H., Owens G.R., Rogers R.M. et al. Does chest physical therapy work? Chest 1985; 88 (3): 436-444.

102. Hess D.R. The evidence for secretion clearance techniques. Respir. Care 2001; 46 (11): 1276-1293.

103. Choe K.H., Kim Y.T., Shim T.S. et al. Closing volume influences the postural effect on oxygenation in unilateral lung disease. Am. J. Respir. Crit. Care Med. 2000; 161 (6): 1957-1962.

104. Clini E.M., Antoni F.D., Vitacca M. et al. Intrapulmonary percussive ventilation in tracheostomized patients: a randomized controlled trial. Intensive Care Med. 2006; 32 (12): 1994-2001.

105. Rosenthal V.D., Guzman S., Safdar N. Reduction in nosocomial infection with improved hand hygiene in intensive care units of a tertiary care hospital in Argentina. Am. J. Infect. Control. 2005; 33 (7): 392-397.

106. Мишнев О.Д., Щеголев А.И. Патологическая анатомия ОРДС. Острый респираторный дистресс-синдром / Под ред. Б.Р.Гельфанда. М.: Литтерра; 2007.

107. Тимофеев И.В. Патология лечения. СПб.: Северо-Запад; 1999.

108. Torres A., Aznar R., Gattel J.M. et al. Incidence, risk, and prognosis factors of nosocomial pneumonia in mechanically ventilated patients. Am. Rev. Respir. Dis. 1990; 142 (3): 523-528.

109. Гульдяев В.Г. Структурные изменения легких и некоторые вопросы патогенеза легочных осложнений при искусственной вентиляции в послеоперационном периоде. Автореф. дис. … канд. мед. наук. М.; 1977.

110. Dos Santos C.C., Slutsky A.S. Mechanotransduction, ventilator-induced lung injury and multiple organ dysfunction syndrome. Intensive Care Med. 2000; 26 (5): 638-642.

111. Escande B., Kuhn P., Rivera S. et al. Secondary surfactant deficiencies. Arch. Pediatr. 2004; 11 (11): 1351-1359.

112. Пермяков Н.К. Патология реанимации и интенсивной терапии. М.: Медицина; 1985.

113. Голубев А.М., Мороз В.В., Лысенко Д.В. и др. ИВЛ-индуцированное острое повреждение легких (экспериментальное, морфологическое иследование). Общая реаниматология 2006; 4: 8-11.

114. Fabregas N., Torres A., El&Ebiary M. et al. Histopathologic and microbiologic aspects of ventilator-associated pneumonia. Anesthesiology 1996; 84 (4): 760-71.

115. Rouby J.J. Histology and microbiology of ventilator-associated pneumonias. Semin. Respir. Infect. 1996; 11 (1): 54-61.

116. Kuhn Ch. et al. Infections of the lung. In: Anderson's Pathology. 10th ed. St. Louis: Mosby Inc.; 1996. 1488-1498.

117. Robbins and Cotran pathologic basis of disease. Philadelphia; London: Elsevier; 2004.

118. Britigan B.E., Roeder T.L., Rasmussen G.T. et al. Interaction of the Pseudomonas aeruginosa secretory products pyocyanin and pyochelin generates hydroxyl radical and causes synergistic damage to endothelial cells. Implications for Pseudomonas-associated tissue injury. J. Clin. Invest. 1992; 90 (6): 2187-2196.

119. Zurn L., Schafnitzl I. The possibility of artificial pneumococcal infection in intratracheal anesthesia. Langenbecks Arch. Klin. 1952; 271 (6): 540-546.

120. Matsubara O., Takumara T., Nasu M. et al. Pathological changes of the lungs after prolonged inhalation of high concentrations of oxygen. Virch. Arch. Abt. A: Pathol Anat. Histopathol. 1986; 408 (5): 461-474.

121. Papazian L., Thomas P., Bregeon F. et al. Open-lung biopsy in patients with acute respiratory distress syndrome. Anesthesiology 1998; 88 (4): 935-944.