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Review  |   September 2016
The Potential of Osteopathic Manipulative Treatment in Antimicrobial Stewardship: A Narrative Review
Author Notes
  •  * Address correspondence to Donald R. Noll, DO, Professor of Medicine, Department of Geriatrics and Gerontology, New Jersey Institute for Successful Aging, Rowan University School of Osteopathic Medicine, 42 E Laurel Rd, Suite 1800, Stratford, NJ 08084-1338. E-mail: nolldr@rowan.edu
     
Article Information
Review   |   September 2016
The Potential of Osteopathic Manipulative Treatment in Antimicrobial Stewardship: A Narrative Review
The Journal of the American Osteopathic Association, September 2016, Vol. 116, 600-608. doi:10.7556/jaoa.2016.119
The Journal of the American Osteopathic Association, September 2016, Vol. 116, 600-608. doi:10.7556/jaoa.2016.119
Web of Science® Times Cited: 1
Abstract

The contemporary management of infectious diseases is built around antimicrobial therapy. However, the development of antimicrobial resistance threatens to create a post–antibiotic era. Antimicrobial stewardship attempts to reduce the development of antimicrobial resistance by improving their appropriate use. Osteopathic manipulative treatment as an adjunctive treatment has the potential for enhancing antimicrobial stewardship by enhancing the human immune system, shortening the duration of antimicrobial therapy, reducing complications, and improving treatment outcomes. The present article reviews the evidence published in the literature since this unique treatment approach was first developed more than 100 years ago. The evidence suggests that adjunctive osteopathic manipulative treatment has great potential for enhancing antimicrobial stewardship and should be further investigated.

There are 2 strategies for treating patients with infectious disease. The first is to target the organism with an appropriate antimicrobial agent. In 1907, Paul Ehrlich developed his “magic bullet” arsphenamine (Salvarsan) and thus began the modern antibiotic era.1 Since then the number of safe and effective antimicrobials has greatly increased1 so that today the treatment of patients with infectious disease is built around the use of antimicrobials.2 The second strategy is to support and enhance the human immune system so that the body will heal itself. Supportive care interventions fall into the latter category as they stabilize the patient long enough for the human immune system to mount an effective defense. Examples of supportive care interventions include administration of intravenous fluids, management of comorbidities, surgical drainage of abscesses, vaccination, nutritional support, incentive spirometry, chest physiotherapy, and early mobilization. Antimicrobial therapy is so central to contemporary management of infectious diseases that all other interventions are considered to be adjunctive and have been given relatively little attention. 
Concerns are growing about antimicrobial resistance and are triggering calls for increased antimicrobial stewardship.2-4 The World Health Organization report on global antimicrobial resistance states that a post–antibiotic era—in which common infections and minor injuries can kill—is far from being an apocalyptic fantasy but is instead a very real possibility for the 21st century.5 Antimicrobial stewardship seeks to optimize the appropriate use of antibiotics with the goal of minimizing the development of antimicrobial resistance.3,6 Antimicrobial stewardship programs are formal efforts to avoid the overuse and misuse of antibiotics.7 Strategies for enhancing antimicrobial stewardship include surveillance for antimicrobial resistance; improved use through education, clinical practice guidelines, and policy; communication training; and enhanced laboratory testing, including the use of biomarkers to confirm infection.3,6 One intervention not discussed in these systematic reviews3,6 that has the potential to enhance antimicrobial stewardship is osteopathic manipulative treatment (OMT). 
When OMT was first developed more than 100 years ago, infectious diseases were the dominant cause of morbidity and mortality.4 It was the death of his 3 children from an infectious disease that was a major impetus for Andrew Taylor Still, MD, DO, to develop OMT.8 In his autobiography, Still attributed the deaths to spinal meningitis but later blamed the deaths of his 3 children on a contaminated water supply.8,9 Many OMT techniques were created specifically to treat patients with infections, regardless of the cause.10 Early osteopathic physicians (ie, DOs) dreamed of defeating all infectious diseases by enhancing the human immune system using OMT.11,12 In an essay discussing pneumonia, Still outlined his underpinning philosophy that health is the result of a perfectly adjusted body and that disease is caused by the failure of the “osteopathic engineer” to obtain the normal position of every bone, muscle, and nerve.13 The classic osteopathic view is that OMT added to antimicrobial therapy will improve the chances of recovery from any infection.14,15 Contemporary DOs still believe in OMT’s potential role in managing infectious diseases, such as in the event of a serious influenza pandemic.16 This article reviews the evidence for using OMT as an adjunctive treatment to antimicrobial therapy and its potential role in antimicrobial stewardship. 
Mechanistic Evidence
In 1912, C.A. Whiting, ScD, DO, studied the effects of liver and splenic stimulation on immune function using rhythmic compressions.17 A phagocytic index was obtained by collecting serum leukocytes and measuring the average number of bacilli ingested by 100 leukocytes. His study design was a simple collection of baseline blood samples, mechanical stimulation of the liver and spleen, and then collection of posttreatment blood samples at various times after treatment.17 A contemporary statistical analysis of his raw data (Table) suggests that liver and splenic stimulation does increase the phagocytic index over baseline for the first 2 hours after treatment. In the 1930s, Yale Castlio, DO, and Louise Ferris-Swift, DO, studied the effect of the splenic pump technique on individuals hospitalized for various infectious diseases.18 They collected baseline blood samples on 100 individuals, applied the splenic pump technique, and then drew 2 posttreatment blood samples at 7 different time intervals, allowing for paired comparisons of 25 or 50 individuals. A contemporary analysis19 of their raw data showed that the splenic pump modestly increased serum white blood cell counts, reduced red blood cell counts, decreased the Arnath index, and increased serum reticulocyte counts. The most robust changes from baseline were the immune function tests. Splenic pumping significantly improved the mean phagocytic index, the opsonic index, the serum agglutinative power, and the serum bacteriolytic power after treatment.19 
Table.
Contemporary Analysis of Whiting’s 1912 Measurements17 of the Phagocytic Index in 2 Patients Who Received Liver and Splenic Stimulation
Hours After Treatment No. of Paired Observations Mean Phagocytic Index 95% CI P Value
Baseline After Treatment
    1 11 4.22 5.68 −2.108 to −0.815 .001
    2  5 4.13 5.31 −1.710 to −0.650 .003
    3 11 4.22 4.63 −0.986 to 0.168 .145
    4  9 4.32 4.39 −0.727 to 0.576 .796
    5  5 4.28 4.21 −0.280 to 0.404 .641
    6  2 4.20 3.43 −5.769 to 7.319 .373
Table.
Contemporary Analysis of Whiting’s 1912 Measurements17 of the Phagocytic Index in 2 Patients Who Received Liver and Splenic Stimulation
Hours After Treatment No. of Paired Observations Mean Phagocytic Index 95% CI P Value
Baseline After Treatment
    1 11 4.22 5.68 −2.108 to −0.815 .001
    2  5 4.13 5.31 −1.710 to −0.650 .003
    3 11 4.22 4.63 −0.986 to 0.168 .145
    4  9 4.32 4.39 −0.727 to 0.576 .796
    5  5 4.28 4.21 −0.280 to 0.404 .641
    6  2 4.20 3.43 −5.769 to 7.319 .373
×
In the 1920s, C.E. Miller, DO, developed the lymphatic pump technique for the express purpose of treating patients with all types of infectious diseases. His idea was that enhancing the lymphatic absorption of toxins (antigens) to the lymphoid tissues would enhance the production of antitoxins (antibodies) to fight infection.20 He originally attempted to do this by having the patient lie supine on the treatment table. Standing above the head with the 4 fingers of his hand in the axilla and the thumb just below the clavicle, Miller would gently pull or milk the lymphatic glands.20 By 1927, his technique had evolved by moving the operator’s hands medially to rest just under the clavicles over the terminal points of the thoracic ducts. The operator would apply a rhythmic motion by alternating pressure and release on the thorax, causing the lymphatic ducts to empty when the thorax was depressed and to fill again when the pressure was released.21 Miller coined the term thoracic pump to describe this technique.21 Other variations were quickly developed and are collectively known today as lymphatic pump techniques. 
Lymphatic pumping improved the antibody response to pneumococcal polysaccharide vaccine in healthy male medical students.22 Hepatitis B vaccine antibody titers rose faster in a group receiving lymphatic and splenic pump techniques.23 Dery et al24 were the first to use a rat model to show that rhythmic mechanical pressure in one region of the body enhanced lymph uptake in a distant region. Later, a dog model was developed that showed the flow of lymph through the thoracic duct increased by both abdominal and thoracic pumping, somewhat similar to what treadmill exercise achieves.25 Abdominal lymphatic pumping in the dog model increased both the flow of lymph moving through the thoracic duct and the number of leukocytes in the thoracic lymph, thus greatly increasing the flux of leukocytes moving through the thoracic duct.26 
Lymphatic pump techniques may have little immediate effect on the peripheral white blood cell count differentials, but they affect platelet counts, sub-cell populations, and pro-inflammatory cytokines. Castlio and Ferris-Swift found that splenic pumping had relatively little effect on the percentages of peripheral leukocyte cell types.18,19 In a study of 12 healthy medical students (7 treatment, 5 control), pectoral traction with splenic pumping caused a transient rise in basophils relative to controls, but all other white blood cell types in peripheral circulation were not affected.27 In another study of 20 relatively immobile nursing home residents, an OMT protocol had no effect on the percentages of white blood cell types present in peripheral circulation, but 30 minutes after treatment the platelet counts were significantly reduced in the OMT group relative to the sham group.28 Notable but insignificant decreases were found in the hemoglobin level, hematocrit level, red blood cell count, and absolute number of lymphocyte cells in the OMT group.28 An OMT protocol that used hepatic, splenic, and lymphatic pump techniques in healthy adults failed to show any between-group differences in total and differential white blood cell counts at 5, 30, and 60 minutes after treatment relative to a sham control.29 However, the OMT protocol induced a significant decrease in the proportion of a subpopulation of blood dendritic cells and increased levels of granulocyte–colony-stimulating factor and monocyte chemotactic protein-1 (MCP-1) cytokines after treatment relative to the sham control.29 
Four minutes of lymphatic pump treatment in the dog model significantly increased the flux of these inflammatory mediators from body tissues, through the thoracic lymphatic duct, and into the blood.30 Specifically, lymphatic pump treatment increased the flux of interleukin (IL)-6, IL-8, IL-10, MCP-1, and keratinocyte chemoattractant in both the mesenteric and thoracic duct lymph. The flux through the thoracic lymphatic duct of IL-6 increased by 615%, IL-8 by 944%, IL-10 by 917%, MCP-1 by 1505%, and keratinocyte chemoattractant by 788% relative to pretreatment baseline. Also, the concentration of MCP-1 during treatment was increased in the thoracic duct lymph relative to pretreatment baseline.30 
Rats that were nasally infected with Streptococcal pneumoniae and treated with a lymphatic pump daily for 7 consecutive days had significantly fewer colony-forming units in the lungs 8 days after infection relative to control and sham therapy groups.31 In a similar study, rats given lymphatic pump treatments 3 times per day for 3 consecutive days had significantly fewer S pneumoniae colony-forming units in the lungs relative to control and sham therapy.32 In a third rat study, 3 applications of the lymphatic pump at 24, 48, and 72 hours after inoculation with S pneumoniae significantly reduced the concentration of bacteria in the lungs at 96 hours after inoculation relative to both control and sham therapy groups.33 Treatment with levofloxacin cleared bacteria from the lungs significantly better at 48, 72, and 96 hours after inoculation relative to a saline control, regardless of receiving sham or lymphatic pump therapy. However, when 3 applications of lymphatic pump technique given at 24, 28, and 72 hours after inoculation were added to levofloxacin therapy, then bacteria was cleared from the lungs significantly better than all other intervention groups.33 This study33 provided, to my knowledge, the first direct evidence that the lymphatic pump technique worked synergistically with antimicrobials. 
Clinical Trial Evidence
In the early 1960s, Kline34 conducted the first randomized controlled trial of OMT as an added intervention to antibiotics. He randomly assigned 252 children hospitalized for various respiratory tract infections into 1 of 3 groups: the first group received OMT, the second group received antibiotics, and the third group received OMT plus antibiotics. All patients received supportive care such as respiratory treatments and intravenous fluid support. The OMT in this study consisted of regular rib raising sessions that varied in frequency by the age of the patient and apparently did not involve lymphatic pump treatments. The mean hospital length of stay (LOS) was 6.3 days for the OMT group, 5.8 days for the antibiotic treatment group, and 4.8 days for the OMT plus antibiotic treatment group, suggesting that OMT complements antibiotic therapy.34 This clinical trial compared OMT, antibiotics, and OMT with antibiotics and showed that OMT alone was not as good as antibiotics alone, but the combination was better than either alone. A limitation of this study was that the statistical significance of these differences in mean LOS was not reported. 
A controlled trial of 57 children with a history of 3 episodes of otitis media in the past 6 months found that adjunctive OMT significantly reduced the number of recurrent otitis media episodes and the need for surgical procedures relative to routine pediatric care.35 In a clinical trial of 22 nursing home residents who received their annual influenza vaccine the first week of October, patients received 10 treatment sessions of either OMT or sham treatment over 4 weeks.36 The treatment group received a semistandardized 15-minute OMT protocol that included paraspinal muscle inhibition, rib raising, myofascial release to the thoracic inlet, myofascial release to the diaphragm, thoracic lymphatic pump with activation, and splenic pump. The sham treatment protocol consisted of light touch applied to the same anatomic areas for approximately the same duration as the OMT protocol. This sham protocol was effective for introducing uncertainty of group assignment among the study participants.37 At the end of the study, participants were asked which group they thought they were in; 43% of participants in both groups said the OMT group, and the rest of the participants said they were unsure. Although OMT failed to improve immunoglobulin (Ig) M and IgG antibody titers 1, 2, 3, and 4 weeks after vaccination relative to the sham group, the mean total days receiving antibiotics from October through March was significantly reduced in the OMT group (10.7 days for the OMT group and 25.0 days for the sham group).36 The month with the most significant difference in mean days receiving antibiotics was January: 0.9 days for the OMT group and 5.5 days for the sham group. In another study involving nursing home residents, twice-monthly OMT and sham treatments over 5 months reduced the number of all-cause hospitalizations relative to a third treat-as-usual group.38 
A randomized controlled trial of 21 elderly patients hospitalized for pneumonia found a mean LOS of 13.5 days for the OMT group and 15.8 days for the control group, but the difference was not statistically significant.39 In a larger study of 58 elderly patients hospitalized for pneumonia, OMT significantly reduced the mean LOS and number of days receiving intravenous antibiotics.39 The mean LOS for the OMT group was 6.6 days vs 8.1 days in the conventional care only group. In the treatment group, OMT reduced duration of intravenous antibiotics by 2 days and reduced total duration of all antibiotics in the hospital by 3 days.39 
The Multicenter Osteopathic Pneumonia Study in the Elderly (MOPSE) showed that patients aged 50 years or older who received a standardized OMT protocol had a statistically significant reduction in LOS relative to those who received conventional care only.40 The mean LOS was 4 days for the OMT group, 4.4 days for a light touch group, and 4.5 days for the conventional care only group. The mean duration of intravenous antibiotics was likewise reduced in the OMT group relative to the conventional care group (3.4 days for the OMT group, 3.7 days for the light touch group, and 3.9 days for the conventional care only group). Those patients who received OMT twice daily for the duration of their hospital stay had lower all-cause mortality and respiratory failure rates compared with those who received conventional care.40 
Therapeutic Mobilization
In MOPSE, the light touch group outcomes often fell between OMT and conventional care only groups, not being statistically different from either, making interpretation problematic. Other studies that used a 3-group study design (treatment, sham, and usual care only groups) have reported similar outcomes.33,38 This outcome pattern is hard to explain. One explanation is that sham protocols can create an early mobilization effect. For example, in MOPSE, being in the sham light touch group meant more frequent changes in position were required to accommodate the twice-daily protocol treatments, whereas being in the conventional care only group meant no extra mobilization. The light touch protocol was given in bed, so patients who were out of bed had to get back in bed. Once in bed, the patients were further shifted about for treatment, and afterward the patients were free to get out of bed. A modest amount of increased mobilization has a surprisingly significant effect. In one clinical trial, the simple intervention of having patients with community-acquired pneumonia get out of bed from day 1 of their hospital stay for 20 minutes per day resulted in a small but significant reduction in LOS.41 
Early mobilization refers to the application of physical activity, either active or passive, within the first few days of the hospital stay.42 A recent review of the literature found that for adult patients in the intensive care unit, early mobilization resulted in fewer ventilator-dependent days, shorter stays in the intensive care unit and hospital, and better functional outcomes.43 Passive motion of the legs for just 20 minutes in adult intubated patients reduced pain and lowered serum IL-6 levels.44 In MOPSE, the 15-minute, twice daily protocol treatments may have similar effects to other early mobilization strategies, with the light touch protocol representing a lesser degree of mobilization and OMT representing a greater degree of mobilization. Clinical trials of OMT in pneumonia suggest that it is well tolerated, even in severely ill and frail elderly patients.39,40,45 Pedal and thoracic lymphatic pump techniques do not adversely change intracranial pressure or cerebral perfusion pressure in patients with traumatic brain injuries.46 Osteopathic manipulative treatment has the potential of mobilizing patients who are too impaired to get out of bed. 
Immobility is associated with poor outcomes from infectious diseases. Bedfast nursing home residents are twice as likely to develop urinary tract infections, 2.5 times more likely to develop pneumonia, and 4 times more likely to die of an infectious disease than nonbedfast nursing home residents.47 Multivariate analysis has shown that the greatest single predictor of mortality from pneumonia in elderly persons is immobility, with a very high OR of 9.4.48 For elderly residents of long-term care facilities, immobility was found to be a major risk factor for other types of lower respiratory tract infections besides pneumonia.49 Implementing a protocol to progressively improve mobility daily in a neurointensive care unit reduces LOS in the unit and hospital, number of hospital-acquired infections, and number of ventilator-associated pneumonias.50 
A few mechanical devices have been developed to mobilize immobile patients. The best known is rotational bed therapy (also known as kinetic therapy), which consists of using a programmable bed that turns on its longitudinal axis either continually or intermittently, between 25° to 65°. Rotational bed therapy decreases the incidence of infections, pneumonia, sepsis, and urinary tract infections.51 A meta-analysis of 35 studies between 1987 and 2004 suggested that rotational bed therapy in selected critically ill patients decreased the incident of pneumonia but had no effect on duration of mechanical ventilation, number of days in the intensive care unit, or hospital mortality.52 Limitations of rotational bed therapy included poor tolerance (patients generally need to be unconscious) and interference with nursing care. A major difference between rotational bed therapy and osteopathic lymphatic pump techniques is that rotational beds slowly rotate around the longitudinal axis, whereas lymphatic pump techniques generally move the patient back and forth in a craniocaudal direction, which should be much better for lymphatic circulation. 
A lesser-known mechanical technique termed whole body periodic acceleration (WBPA) uses a motorized platform (a mechanical bed) that moves the patient, who lies supine on the device, in a repetitive, sinusoidal, craniocaudal direction.53 This device produces a body motion very similar to what is achieved by the osteopathic pedal pump. It has primarily been studied (using animal models) as an alternative to traditional compressive cardiopulmonary resuscitation and appears to be effective in limiting damage to the myocardium after cardiac arrest.43,54,55 The device also produces neurotherapeutic effects in the myocardium and preserves heart rate variability after cardiac arrest.56,57 Rokutanda et al58 found that WBPA increased blood supply in ischemic lower extremities through activation of endothelial nitric oxide synthase signaling and upregulation of proangiogenic growth factor. It is believed that the pulsatile shear stress to the endothelium generated by WBPA stimulates nitric oxide production and vasodilatation in healthy patients as well as in those with inflammatory diseases.59 One published abstract reported that osteopathic pedal pump also increased serum nitric oxide levels.60 However, WBPA has yet to be studied for its effects on the lymphatic and human immune system. 
Discussion
Sometime near the close of the 19th century, Still was asked by a student if there were any infectious diseases that the body was unable to destroy alone. By implication, the student was asking if there were any infectious diseases that OMT could not treat alone. Still replied “Yes.” So the student pressed him for a more specific answer, and Dr. Still replied “Syphilis.” Then the student asked him, “What would you do?” Still answered, “Until we know something better, I would make the exception in favor of drugs and give mercury.”61 At the time mercurial salts were the primary drug treatment for syphilis, as they are spirillicidal but also very toxic.62 Still’s concession is important because it illustrates the pragmatism he infused into the profession he founded and because it presents the idea of using OMT with antimicrobials to treat a patient with an infectious disease. 
The problem of antimicrobial resistance is here to stay because the natural adaptive response of microorganisms is to develop resistance.7 New approaches must be developed to enhance antimicrobial stewardship. The evidence indicates that adjunctive OMT can enhance the human immune system, shorten the duration of antibiotic therapy, and improve outcomes. However, the evidence for OMT in antimicrobial stewardship remains indirect. It is not known if an active OMT hospital consultation service can reduce antimicrobial resistance rates. Such direct evaluations need to be done. Likewise, research is needed to determine for which types of infections is OMT most effective. Is OMT best for bacterial respiratory tract infections or does it also have potential for viral, fungal, and paracytic infections? As the originator of OMT, the osteopathic medical profession has an obligation to explore OMT’s potential. 
Murray Goldstein, DO, called for the osteopathic medical profession to take responsibility for OMT in pneumonia research by initiating a dues-generated financial set-aside for osteopathic research grants and the development of career physician-investigators.63 Limited funding and a shortage of career physician-investigators limits progress.64,65 Perhaps if the profession meets this challenge, then the full potential of OMT will be realized. 
References
Zaffiri L, Gardner J, Toledo-Pereyra LH. History of antibiotics: from salvarsan to cephalosporins. J Invest Surg. 2012;25(2):67-77. doi:10.3109/08941939.2012.664099. [CrossRef] [PubMed]
Prescott JF. The resistance tsunami, antimicrobial stewardship, and the golden age of microbiology. Vet Microbiol. 2014;171(3-4):273-278. doi:10.1016/j.vetmic.2014.02.035. [CrossRef] [PubMed]
Drekonja DM, Filice GA, Greer N, et al. Antimicrobial stewardship in outpatient settings: a systematic review. Infect Control Hosp Epidemiol. 2015;36(2):142-152. doi:10.1017/ice.2014.41. [CrossRef] [PubMed]
Yoshikawa TT. Antimicrobial resistance and aging: beginning of the end of the antibiotic era? J Am Geriatr Soc. 2002;50(7 suppl):S226-S229. [CrossRef] [PubMed]
World Health Organization. Antimicrobial Resistance: Global Report on Surveillance. Geneva, Switzerland: World Health Organization; 2014.
Zhang YZ, Singh S. Antibiotic stewardship programmes in intensive care units: why, how, and where are they leading us [review]. World J Crit Care Med. 2015;4(1):13-28. doi:10.5492/wjccm.v4.i1.13. [CrossRef] [PubMed]
Mendelson M. Role of antibiotic stewardship in extending the age of modern medicine [review]. S Afr Med J. 2015;105(5):414-418. doi:10.7196/samj.9635. [CrossRef] [PubMed]
Still AT. Autobiography of Andrew T. Still With a History of the Discovery and Development of the Science of Osteopathy. Kirksville, MO: Published by the author; 1897.
Still AT. Osteopathy Research and Practice. Kirksville, MO: Published by the author; 1910.
Noll DR, Degenhardt BF, Fossum C, Hensel K. Clinical and research protocol for osteopathic manipulative treatment of elderly patients with pneumonia. J Am Osteopath Assoc. 2008;108(9):508-516. [PubMed]
Lane MA. Dr. A.T. Still, Founder of Osteopathy. Chicago, IL: The Osteopathic Publishing Co.; 1918.
Thorburn AL. Paul Ehrlich: pioneer of chemotherapy and cure by arsenic (1854-1915). Br J Vener Dis. 1983;59(6):404-405. [PubMed]
Still AT. Pneumonia. J Am Osteopath Assoc. 1907;14(12):421-422.
Rumney IC. Osteopathic manipulative treatment of infectious diseases. Osteopathic Annals. 1974;(July):29-33.
Chila AG. Helping bodies help themselves. Consultant. 1982:174-188.
Hruby RJ, Hoffman KN. Avian influenza: an osteopathic component to treatment. Osteopath Med Prim Care. 2007;1:10. [CrossRef] [PubMed]
Whiting CA. Investigations of the opsonic index. J Am Osteopath Assoc. 1912;12(9):20-21.
Castlio Y, Ferris-Swift L. The effect of direct splenic stimulation on the cells and antibody content of the blood stream in acute infectious diseases. The College Journal of the Kansas City College of Osteopathy. 1934;18(7):196-211. Reprinted in: Academy of Applied Osteopathy Year Book. 1955:1121-1137.
Noll DR, Johnson JC, Brooks JE. Revisiting Castlio and Ferris-Swift’s experiments on direct splenic stimulation in patients with acute infectious disease. J Am Osteopath Assoc. 2008;108(2):71-79. [PubMed]
Miller CE. Osteopathic treatment of acute infections by means of the lymphatics. J Am Osteopath Assoc. 1920;19:494-499.
Miller CE. The specific cure of pneumonia. J Am Osteopath Assoc. 1927;27(9):35-38.
Measel JWJr. The effect of the lymphatic pump on the immune response: I—preliminary studies on the antibody response to pneumococcal polysaccharide assayed by bacterial agglutination and passive hemagglutination. J Am Osteopath Assoc. 1982;82(1):28-31. [PubMed]
Jackson KM, Steele TF, Dugan EP, Kukulka G, Blue W, Roberts A. Effect of lymphatic and splenic pump techniques on the antibody response to hepatitis B vaccine: a pilot study. J Am Osteopath Assoc. 1998;98(3):155-160. [PubMed]
Dery MA, Yonuschot G, Winterson BJ. The effects of manually applied intermittent pulsation pressure to rat ventral thorax on lymph transport. Lymphology. 2000;33(2):58-61. [PubMed]
Knott EM, Tune JD, Stoll ST, Downey HF. Increased lymphatic flow in the thoracic duct during manipulative intervention. J Am Osteopath Assoc. 2005;105(10):447-456. [PubMed]
Hodge LM, King HH, Williams AGJr, et al. Abdominal lymphatic pump treatment increases leukocyte count and flux in thoracic duct lymph. Lymphat Res Biol. 2007;5(2):127-133. [CrossRef] [PubMed]
Mesina J, Hampton D, Evans R, et al. Transient basophilia following the application of lymphatic pump techniques: a pilot study. J Am Osteopath Assoc. 1998;98(2):91-94. [PubMed]
Noll DR. The short-term effect of a lymphatic pump protocol on blood cell counts in nursing home residents with limited mobility: a pilot study. J Am Osteopath Assoc. 2013;113(7):520-528. doi:10.7556/jaoa.2013.003. [CrossRef] [PubMed]
Walkowski S, Singh M, Puertas J, Pate M, Goodrum K, Benencia F. Osteopathic manipulative therapy induces early plasma cytokine release and mobilization of a population of blood dendritic cells. PLoS One. 2014;9(3):e90132. doi:10.1371/journal.pone.0090132. [CrossRef] [PubMed]
Schander A, Downey HF, Hodge LM. Lymphatic pump manipulation mobilizes inflammatory mediators into lymphatic circulation. Exp Biol Med (Maywood). 2012;237(1):58-63. doi:10.1258/ebm.2011.011220. [CrossRef] [PubMed]
Hodge LM. Osteopathic lymphatic pump techniques to enhance immunity and treat pneumonia. Int J Osteopath Med. 2011;15(1):13-21. [CrossRef]
Creasy C, Schander A, Orlowski A, Hodge LM. Thoracic and abdominal lymphatic pump techniques inhibit the growth of S pneumoniae bacteria in the lungs of rats. Lymphat Res Biol. 2013;11(3):183-186. doi:10.1089/lrb.2013.0007. [CrossRef] [PubMed]
Hodge LM, Creasy C, Carter K, Orlowski A, Schander A, King HH. Lymphatic pump treatment as an adjunct to antibiotics for pneumonia in a rat model. J Am Osteopath Assoc. 2015;115(5):306-316. doi:10.7556/jaoa.2015.061. [CrossRef] [PubMed]
Kline CA. Osteopathic manipulative therapy, antibiotics, and supportive therapy in respiratory infections in children: comparative study. J Am Osteopath Assoc. 1965;65(3):278-281. [PubMed]
Mills MV, Henley CE, Barnes LL, Carreiro JE, Degenhardt BF. The use of osteopathic manipulative treatment as adjuvant therapy in children with recurrent acute otitis media. Arch Pediatr Adolesc Med. 2003;157(9):861-866. [CrossRef] [PubMed]
Noll DR, Degenhardt BF, Stuart MK, Werden S, McGovern RJ, Johnson JC. The effect of osteopathic manipulative treatment on immune response to the influenza vaccine in nursing homes residents: a pilot study. Altern Ther Health Med. 2004;10(4):74-76. [PubMed]
Noll DR, Degenhardt BF, Stuart M, McGovern R, Matteson M. Effectiveness of a sham protocol and adverse effects in a clinical trial of osteopathic manipulative treatment in nursing home patients. J Am Osteopath Assoc. 2004;104(3):107-113. [PubMed]
Snider KT, Snider EJ, Johnson JC, Hagan C, Schoenwald C. Preventative osteopathic manipulative treatment and the elderly nursing home resident: a pilot study. J Am Osteopath Assoc. 2012;112(8):489-501. [PubMed]
Noll DR, Shores J, Bryman PN, Masterson EV. Adjunctive osteopathic manipulative treatment in the elderly hospitalized with pneumonia: a pilot study. J Am Osteopath Assoc. 1999;99(3): 143-146, 151-142.
Noll DR, Degenhardt BF, Morley TF, et al. Efficacy of osteopathic manipulation as an adjunctive treatment for hospitalized patients with pneumonia: a randomized controlled trial. Osteopath Med Prim Care. 2010;4:2. doi:10.1186/1750-4732-4-2. [CrossRef] [PubMed]
Mundy LM, Leet TL, Darst K, Schnitzler MA, Dunagan WC. Early mobilization of patients hospitalized with community-acquired pneumonia. Chest. 2003;124(3):883-889. [CrossRef] [PubMed]
Hodgson CL, Berney S, Harrold M, Saxena M, Bellomo R. Clinical review: early patient mobilization in the ICU. Crit Care. 2013;17(1):207. doi:10.1186/cc11820. [CrossRef] [PubMed]
Cameron S, Ball I, Cepinskas G, et al. Early mobilization in the critical care unit: a review of adult and pediatric literature. J Crit Care. 2015;30(4):664-672. doi:10.1016/j.jcrc.2015.03.032. [CrossRef] [PubMed]
Amidei C, Sole ML. Physiological responses to passive exercise in adults receiving mechanical ventilation. Am J Crit Care. 2013;22(4):337-348. doi:10.4037/ajcc2013284. [CrossRef] [PubMed]
Noll DR, Shores JH, Gamber RG, Herron KM, Swift JJr. Benefits of osteopathic manipulative treatment for hospitalized elderly patients with pneumonia. J Am Osteopath Assoc. 2000;100(12):776-782. [PubMed]
Cramer D, Miulli DE, Valcore JC, et al. Effect of pedal pump and thoracic pump techniques on intracranial pressure in patients with traumatic brain injuries. J Am Osteopath Assoc. 2010;110(4):232-238. [PubMed]
Beck-Sague C, Banerjee S, Jarvis WR. Infectious diseases and mortality among US nursing home residents. Am J Public Health. 1993;83(12):1739-1742. [CrossRef] [PubMed]
Wawruch M, Krcmery S, Bozekova L, et al. Factors influencing prognosis of pneumonia in elderly patients. Aging Clin Exp Res. 2004;16(6):467-471. [CrossRef] [PubMed]
Loeb M, McGeer A, McArthur M, Walter S, Simor AE. Risk factors for pneumonia and other lower respiratory tract infections in elderly residents of long-term care facilities. Arch Intern Med. 1999;159(17):2058-2064. [CrossRef] [PubMed]
Titsworth WL, Hester J, Correia T, et al. The effect of increased mobility on morbidity in the neurointensive care unit. J Neurosurg. 2012;116(6):1379-1388. doi:10.3171/2012.2.JNS111881. [CrossRef] [PubMed]
Kelley RE, Vibulsresth S, Bell L, Duncan RC. Evaluation of kinetic therapy in the prevention of complications of prolonged bed rest secondary to stroke. Stroke. 1987;18(3):638-642. [CrossRef] [PubMed]
Goldhill DR, Imhoff M, McLean B, Waldmann C. Rotational bed therapy to prevent and treat respiratory complications: a review and meta-analysis. Am J Crit Care. 2007;16(1):50-61. [PubMed]
Uryash A, Wu H, Bassuk J, Kurlansky P, Adams JA. Preconditioning with periodic acceleration (pGz) provides second window of cardioprotection. Life Sci. 2012;91(5-6):178-185. doi:10.1016/j.lfs.2012.06.031. [CrossRef] [PubMed]
Adams JA, Bassuk J, Wu D, Grana M, Kurlansky P, Sackner MA. Periodic acceleration: effects on vasoactive, fibrinolytic, and coagulation factors. J Appl Physiol. 2005;98(3):1083-1090. [CrossRef] [PubMed]
Adams JA, Uryash A, Wu H, et al. Microcirculatory and therapeutic effects of whole body periodic acceleration (pGz) applied after cardiac arrest in pigs. Resuscitation. 2011;82(6):767-775. doi:10.1016/j.resuscitation.2011.02.012. [CrossRef] [PubMed]
Adams JA, Uryash A, Bassuk J, Sackner MA, Kurlansky P. Biological basis of neuroprotection and neurotherapeutic effects of Whole Body Periodic Acceleration (pGz). Med Hypotheses. 2014;82(6):681-687. doi:10.1016/j.mehy.2014.02.031. [CrossRef] [PubMed]
Adams JA, Uryash A, Nadkarni V, Berg RA, Lopez JR. Whole body periodic acceleration (pGz) preserves heart rate variability after cardiac arrest. Resuscitation. 2016;99:20-25. doi:10.1016/j.resuscitation.2015.11.018. [CrossRef] [PubMed]
Rokutanda T, Izumiya Y, Miura M, et al. Passive exercise using whole-body periodic acceleration enhances blood supply to ischemic hindlimb. Arterioscler Thromb Vasc Biol. 2011;31(12):2872-2880. doi:10.1161/ATVBAHA.111.229773. [CrossRef] [PubMed]
Sackner MA, Gummels E, Adams JA. Nitric oxide is released into circulation with whole-body, periodic acceleration. Chest. 2005;127(1):30-39. [CrossRef] [PubMed]
Overberger R, Hoyt JA, Daghigh F, et al. Comparing changes in serum nitric oxide levels and heat rate after osteopathic manipulative treatment (OMT) using the dalrymple pedal pump to changes measured after active exercise [abstract S22]. J Am Osteopath Assoc. 2009;109(1):42-43.
Ligon EB. Some things Dr. Still told me. J Am Osteopath Assoc. 1924;24(7):814-818.
O’Shea JG. ‘Two minutes with venus, two years with mercury’—mercury as an antisyphilitic chemotherapeutic agent. J R Soc Med. 1990;83(6):392-395. [PubMed]
Goldstein M. Osteopathic manipulative treatment for pneumonia. Osteopath Med Prim Care. 2010;4(1):3. doi:10.1186/1750-4732-4-3. [CrossRef] [PubMed]
Noll DR. Response [letter]. J Am Osteopath Assoc. 2014;114(2):81-82. doi:10.7556/jaoa.2014.019. [CrossRef] [PubMed]
Noll DR. Evidence-based medicine and osteopathic medicine: no paradox. J Am Osteopath Assoc. 2015;115(3):124-125. doi:10.7556/jaoa.2015.024. [PubMed]
Table.
Contemporary Analysis of Whiting’s 1912 Measurements17 of the Phagocytic Index in 2 Patients Who Received Liver and Splenic Stimulation
Hours After Treatment No. of Paired Observations Mean Phagocytic Index 95% CI P Value
Baseline After Treatment
    1 11 4.22 5.68 −2.108 to −0.815 .001
    2  5 4.13 5.31 −1.710 to −0.650 .003
    3 11 4.22 4.63 −0.986 to 0.168 .145
    4  9 4.32 4.39 −0.727 to 0.576 .796
    5  5 4.28 4.21 −0.280 to 0.404 .641
    6  2 4.20 3.43 −5.769 to 7.319 .373
Table.
Contemporary Analysis of Whiting’s 1912 Measurements17 of the Phagocytic Index in 2 Patients Who Received Liver and Splenic Stimulation
Hours After Treatment No. of Paired Observations Mean Phagocytic Index 95% CI P Value
Baseline After Treatment
    1 11 4.22 5.68 −2.108 to −0.815 .001
    2  5 4.13 5.31 −1.710 to −0.650 .003
    3 11 4.22 4.63 −0.986 to 0.168 .145
    4  9 4.32 4.39 −0.727 to 0.576 .796
    5  5 4.28 4.21 −0.280 to 0.404 .641
    6  2 4.20 3.43 −5.769 to 7.319 .373
×