The effect of external ultrasound waves on ecchymosis, edema and pain after facial aesthetic surgery

The effect of external ultrasound waves on ecchymosis, edema and pain after facial aesthetic surgery

Mohammed Taher Ahmed Omar,a PTD;

Khaled EG,c  MD; Ahmed A Hassan,c MD;  Roqua Sabagh Mostafa,d MD

a) Department of Physical  Therapy  for surgery, Faculty  of Physical  Therapy, Cairo, Egypt.

b) Member of Rehabilitation Research Chair, College  of Applied Medical

Science,  King Saud University.

c)  Department of Plastic Surgery, Ain Shams  University, Cairo, Egypt.

d) Department of Physical  Therapy  Department, El-Matria Teaching Hospital, Cairo, Egypt.

Corresponding Author: Mohammed Taher Ahmed Omar

Email address: Dr.Taher_M@Yahoo.Com - M omarar@ksu.edu.Sa

Mobile  phone  +20101547585- +960542115404

Faculty  of Physical  Therapy, Cairo University;

7 Ahmad Alzayat St., Bain Elsarayat,  Giza, Egypt.

Abstract

Background and objective: Facial cosmetic procedures are often associated with unsightly postoperative ecchymosis, and swelling, which may be a source of pain and anxiety for patients and can be difficult to camouflage. This study was conducted to assess the safety and efficacy of low frequency 3MHz pulsed ultrasound (US) in the treatment of ecchymosis and swelling after facial cosmetic procedures.

Methods:   Thirty  patients  undergoing   facial  cosmetic   surgery  had  been  involved   and randomly divided into two equal groups. Ultrasound group (US-group, n=15), who received

3MHzpulsed US at 1.5 W/cm2for 5 minutes to each side of the face, and control group (n=15). Postoperative  assessment included  severity of ecchymosis,  postoperative  pain, and amount of facial swelling. All measurements were performed by blinded investigator at postoperative days (P0Ds).l,3,5,7,10

Results: Complete resolution of ecchymosis, pain and facial swelling was observed between POD5 toPOD7 in US group. While in control group resolution and reduction of pain and facial swelling occurred at POD7 to POD10.

Conclusion:  Postoperative  US therapy  helps in  early resolution  and  reduction  of facial swelling and pain after facial cosmetic surgery with no reported complications or side effects.

Key words: Ultrasound, facial cosmetic surgery, ecchymosis, edema, pain.

Introduction:

Facial aesthetic surgenes are often associated   with   postoperative   ecchymosis and edema. These may be a source  of pain

and anxiety for patients and can be difficult to camouflage. Ecchymosed and edematous tissue may require 10 days or more to resolve and potentially  can limit social activities.1,2

Postoperative  edema occurs due to  changes in the  capillary  hemodynamic,  loss  of vascular integrity and lymphatic obstruction that collectively lead to accumulation of fluid in the tissue and result in visible swelling of the face.2

Ultrasound (US) has been used as a therapeutic modality for several decades, mainly by physiotherapists to treat soft-tissue injuries.3,4 Claims have been made that US modifies both the acute and chronic  phases of inflammation. This led to reduction of edema,  relieves  pain,  encourages  healing, and modifies scar formation.5-7

The US is capable of producing therapeutic thermal and non-thermal effects in the tissues.6,8,9 The thermal  effects may include increased blood flow, reduction of muscle spasm,  increased  tissue  extensibility,  and  a mild inflammatory  response. It is estimated that the thermal  effects occur with elevation of  tissue  temperature  to  be  40-45°c  for  at least 5 minutes.31

It has been suggested that the non-thermal effects, including cavitations and acoustic microstreaming,  are more important in the treatment   of   soft-tissue   lesions   than   are the thermal  effects.32 These may  cause stimulation of fibroblast activity, increased protein synthesis,  increased  blood flow, and tissue regeneration.9

Despite  the   frequent   use   of  US   with reported success to clinical practice,8-12 its effect following  facial  aesthetic surgery has not been reported in the literature.  Therefore, this study was designed to study and assess the   efficacy   of  3MHz   pulsed   mode   US therapy on ecchymosis, edema, and pain after facial aesthetic surgeries.

Patients and methods:

The study included 30 patients who underwent  surgical  aesthetic  procedures  to the face from  June 2008 to December 2010. The age ofthe patients ranged from 21 to 52 years old with an average age of 39 years. Patients who have had hypertension, diabetes, and  abnormal  bleeding  and/or  clotting profiles   were   excluded   from   the   study. All  patients  were  instructed  to  stop  taking

aspmn,   non-steroidal   anti-inflammatory drugs,  vitamin  E,  and smoking  for  2-week prior surgery.  All surgical procedures were performed by consultant author. The surgical procedures     included     open     rhinoplasty, facial contouring with fat injection, and blepharoplasty. No intraoperative homeostatic agents or drain were used. The patients were randomly  assigned  to  ultrasound  group (no=15) or control group (no=15) using enveloped methods.

Ultrasormd exposure protocol:

The US therapy was conducted using (US-

700   ITO  CO.,  LTD-Tokyo-Japan)  3MHz, with duty cycle of 20% and intensity  of 0.5

W/cm2. The transducer  head had an area of

5.2cm2, with  an effective  radiating  area  of

5cm2.    Sterilized  US  coupling  media  was applied to the skin. Then the US transducer head   was  placed   firmly   on  the   targeted skin  surface,   and  pressed  uniformly   with rhythmical  circular  movement  for  lowering the power of the US transmission to maintain constant  responses.2  After  US  application, gel was wiped  off. Patients  were instructed that  if they  encountered  any  other  effects, they  should  contact  the  therapist  promptly. The US therapy  was administered  daily, for

7 minutes on each side ofthe face starting at POD3 until the PODlO or until the signs, and symptoms resolved.

Postoperative care:

In all patients, standard pressure dressings were applied at the end of the procedure for 48 hours. Cryotherapy was applied to the surgical sites for the first 48 hours, which is routine in our practice. Cryotherapy  was applied using

9-inch rounded-shaped ice bags and cold gel

packs. The ice bag was applied to the surgical wound with the patient in the supine position with a head elevation  of 30 degrees.  At the same  time,  glasses-shaped   cold  gel  packs were attached to the periorbital area with Velcro  tape.  Cryotherapy   was  applied  for

20 minutes per hour, beginning  three  hours

postoperatively,    every   hour   except   from

1Opm-1Oam. Cryotherapy  was  applied  by patients  or caregivers  after education  about

the protocol.  Follow-up  was made three times per day to confirm adequate application of the intervention.

The physician supplied the medications to ensure compliance. Diclofenac K (Novartis, Switzerland) was given 50 mg, 3 times  daily for five days. All patients were placed on a five­ day antibiotic regimen  (500mg ampicillin­ cloxacillin, Smith-  Kline Beecham,  England;

4 times  daily).  All the medications were administered orally.

Clinical assessment:

All patients were seen for assessment preoperatively      and      on      PODs),3,5,7,10

Standard photographs were taken  before  and after treatment for the presence  and  changes of ecchymosis and edema.

Ecchymosis;  each   patient   was  digitally

photographed  on  PODs),3,5,7,10  Three blinded  surgeons  evaluated the  photographs and  graded  the  ecchymosis on  a scale  of  0 to 3, where; 0, no ecchymosis, 1, minimal ecchymosis,  2,   moderate    ecchymosis,  3, severe   ecchymosis.  Average   mean   scores were  computed for  all three  observers.  The statistical analysis  was performed on the difference  between the means scores.l

Pain assessment:

Patients  were  instructed to  quantify  their postoperative pain level in the morning of 10 consecutive days using visual  analogue  scale (VAS)  prior  to  taking  any  pain  medication. The  VAS  consisted of  1Ocm  line  anchored at one end by the  label  'No  pain' and  at the other   end   by   'Worst   possible   pain'.   The patient marked on the line spot for the pain intensity which  was then  measured.lO  Pain intensity was categorized into  0 as no  pain,

1-3 as mild  pain, 4--6 as moderate  pain, 7-9 as severe pain and 10 as worst pain.

Facial edema assessment:

As no published method satisfies all criteria for  assessing facial  swelling, we decided  to use a measuring tape to measure  facial  width and  swelling. The  reference  points  distance used were the;ll,l 2

1-Tragus- mental protuberance.

2-Tragus- mouth  angle (comer  of mouth).

3-Mandibular angle-nasal alae.

4-Mandibular angle- external  eye angle.

5-Mandibular angle- internal  eye angle.

6-Mentalprotuberance- external eye angle.

7-Mandibular angle-mental protuberance. A single   blinded  therapist evaluated the amount of swelling by distance measurements performed       between           these    well                      defined anatomical  landmarks.  The   procedure  was repeated  three times  on each patient,  and the average was then taken (in em) and recorded. The extent  of facial  swelling  was  calculated through   the   sum   of   the   following  seven distances  on  each  side  of face  and  divided by two.  The measurements were  carried  out just  before the surgery  and at PODs.l,3,5,7,10

Postoperative swelling   was  expressed  as  a percentage increase in facial width as follows:

Postoperative measurement-  Preoperative measurement X100

Preoperative measurement

Data analysis:

Data were expressed as means±standard deviation (SD) unless otherwise indicated. Statistical differences between the two groups were  tested   with  the  unpaired   t-test.   One­ way analysis  of variance used to determine significance within the group. The ecchymosis scores were compared using a Mann-Whitney test  between  the  groups,   and  Wilcoxon  test within  the groups.  The statistical package  of social science software (SPSS  Inc., Chicago, IL,  USA)  was  used to perform  the analysis. All p values less than 0.05 were considered to be statistically significant.

Results:

Table(l) shows  the clinical  and operative characteristics ofthe patients  who completed the    study.    The   data    regarding   to     age, sex,  duration   and  types   of  surgeries   were comparable  between   groups.   A  subgroup of       patients             undergoing        facial        aesthetic surgeries was  created. They  were  identical in  sex   and  age   distribution,  numbers   and types  of  surgical   procedures.  Postoperative

pain medication  and antibiotic consumed  by each patient within, and between groups was similar.

Ecchymosis:

Figure(l) shows observer's ecchymosis ratings scores according to days. At POD1, severe ecchymosis was reported in (66.7% versus 60%) and moderate ecchymosis in (33.3%   versus  40%)  in  US  group  versus control group. This revealed non significant differences (P>0.05) between the groups.

In the US group, substantial improvement and resolution of ecchymosis was observed between PODS (1.83±0.1S,  p<O.OS), POD7 (0.83±1.33,   p<O.OS) compared   to   POD1 (2.88±0.8S) and POD3 (2.6±0.1S). Mean ecchymosis scores significantly declined to (0.14±0.1S,  p<O.OS), at POD10, with a 9S% improvement.

For       control        group,       improvement

and  resolution  of  ecchymosis  occurred between   POD7  (1.96±0.69,   p<O.OS) to POD10   (0.91±0.4S,   p<O.OS). There   was no improvement in ecchymosis at PODS (2.33±0.4S,   p>O.OS) compared   to   POD1 (2.8S±0.69)   and   POD3   (2.S7±0.69).   The mean  ecchymotic  score  improved  by  86% at POD10. There was a significant reduction of ecchymosis between the US and control groups   on   PODs   S  (p<0.02),   7(p<0.02), and 10(<0.01). In the US group, complete resolution  of  ecchymosis  was  observed  in all patients at POD10.  In the control  group, ecchymosis resolved completely in 8 patients (S3.3%). Moderate ecchymosis has been reported in 3 patients (20%) and 4 patients (26.7%) had mild ecchymosis.

Facial Edema:

Figure(2), represents the mean percentage reduction of facial swelling in both groups. There    was   no   significant   difference   in the average amount of swelling at POD1 (20.7±2.3      versus      19.27±3.2,     p>0.05) and POD3 (20.34±2.3 versus 21.18±3.4, p>0.05) between US and control groups respectively. Treatment with the US resulted in a continuous reduction of percentage of swelling  between  PODS to  POD10.  There

was a statistically significant reduction at PODS (13.93±4.S,  p=0.007), POD7 (8±3.6, p=0.001), and PODlO (3.11±1.88,  p=O.OOl) as   compared   to   POD1   (20.7±S.86)   and POD3   (20.34±4.06).    For   control    group, the swelling was statistically significant at POD7 (11.64±2.4S, p=0.03) and POD10 (7.64±2.48, p= 0.01), while there was no improvement at PODS (18.22±4.4S,  p>O.OS) compared to POD1 (19.27±S.69) and POD3 (21.18±4.69). The percentage of the facial swelling revealed a significant reduction at PODS (32.7% versus S.94%, p=0.01), POD7 (61.3S%  versus 39.S9%,  p=O.OOl), POD10 (84.97%  versus  66.35%,  p=0.001)  for  US group versus control respectively.

Postoperative pain:

Figure  (3) represents  the mean  pain scores. There were no significant differences in average pain intensity at POD1 (6.73±1.S3 versus 6.46±1.S, p=63) and POD3 (3.13±1.S3 versus 4.48±1.5, p=63) between the US and control groups respectively. Chi-square test revealed non statistical significant difference (P>O. 05) in the number of patients reporting severe pain (8; S3.3% versus 7; 46.7%), moderate  pain (7;  46.7%  versus 8; S3.3%) in US and control groups respectively. Treatment with US resulted in a significant reduction  of postoperative  pain between PODS to  POD7.  Pain  subsided  completely in (9 patients; 60%) by PODS, the remaining

6 patients had mild pain (3patients;  20%) to moderate  pain  (3patient;  20%).  On  POD7,

11 patients (73.3%) reported no pain and 4 patients (26.7%)  had mild pain.  At POD10,

13 patients  (86. 7%) reported  no  pain and  2 patients  (13.3%)  had mild pain. For control group, a significant reduction of postoperative pain was observed between PODS to POD10. Pain subsided completely in 3 patients (20%) by  PODS.  The  remaining  12  patients  had mild  pain  (3  patients;   20%)  to  moderate pain (9 patients; 60%).  On POD7, 4 patients (26.7%) reported no pain, and the 9 patients (60%) had mild pain and 2 patients (13.3%) had  moderate  pain. At  PODlO,  6  patients (40%)  reported  no pain, 7 patients  (46.7%) had  mild  pain  and  2  patients  (13.3%)  had

3                                     c US-group         •Controlgroup

Figure (1): Observers ecchymosis ratings scores.

-+-US-group       - Controlgroup I

26

E    20

j

1/)

i·ui 16

-Cll

0            10

"#.

c:

Cll              6

:iell

0

Figure (2): Progress of facial edema. POD: postoperative  day. US: ultrasound.

Figure (3): Average pain scores in visual analogue.

Figure (4): A. 35-year old female patient with thin face. B. 2 days after facial contouring by fat transfer. C. 7 days post operative with marked reduction of facial edema and ecchymosis.

Figure (5):. A. 20-year old male patient with posttraumatic crooked nose. B. 2 weeks postoperative with residual ecchymosis of the face.

Figure (5): A. 26-year old female patient with slim face. B. 2 days after fat injection into cheeks and lips, with profound edema. C. 7 days postoperative with the use of ultrasound treatment showing minimal edema.

Table (1): Patients' characteristics.

US; ultrasound, VAS=visual analogue scale,*  (p>0.05) non significant.

moderate pain. The mean pain scores revealed a statistical significant (P<0.05)  reduction at PODs 5 (1.13+ versus2.4+), POD7 (0.53+ versus   1.93+)  and   PODlO   (0.13+  versus

1.07+)   between US and control groups respectively.

Discussion:

This study examined the results of ultrasound   treatment   in  patients  who  had facial    aesthetic    surgery    confirmed    by clinical  examination  of ecchymosis,  edema and pain. There were significantly greater changes in all parameters for the ultrasound treatment  group compared to control group. We reported that the  maximum  response to ultrasound treatment was between PODS to PODlO. This  effect  was seen in  more than

95% of treated patients, with no recorded side

effects. Therefore, ultrasound appears to be a safe and effective modality for enhancement of early recovery after facial aesthetic surgery when compared to control treatment.

It appears  that  exposure   to  continuous

US during  the  initial  'inflammatory'  phase of  tissue  repair  causes  heat,  which  would increase   blood   flow   and   edema   in   this area.31 In contrary,  pulsed mode  US causes the non-thermal  effect on the tissue  without measurable  temperature changes.  These can lead  to  an  acceleration   of  this  phase  and

reduction ofthe extent oftissue damage.9

The  role  of  non-thermal  mechanisms  of US in tissue regeneration13 and repairl4-17 has also been widely established. At a cellular­ level, it has been hypothesized  that there are changes in diffusion rates and membrane permeability  to ionsl8-20 due to acoustic streaming and stable cavitation. These can stimulate    cell   activity   by    up-regulation of signaling molecules, with associated reduction      of      edema      formation.5,18-21

Moreover, during the inflammatory phase of the healing process, US can activate immune cells to migrate to the site of injury. Fyfe et al. showed induction of mast cell degranulation and   histamine   release   in   injury   models in  vivo  using  pulsed  mode  US  of  0.5W/ cm2_22,23  Similar  results  were  reported  for dermal mast cells, demonstrating that US can accelerate the inflammatory healing phase for skin lesion/ulcers  in vivo (Wistar rats, 0.75-

3MHz,  0.25-3  W/cm2).24  In  related  study,

Young et ai25 showed that ultrasound (3MHz,

0.5 W/cm2) could stimulate  macrophages  in vitro to release fibroblast mitogenic factors, resulting in enhanced fibroblast proliferation.

By  increasing  the  activity  of these  cells,

the overall influence of therapeutic US is certainly pro-inflammatory rather than anti­ inflammatory. Studies which have tried to demonstrate  the anti inflammatory  effect of

ultrasound have failed to do so (e.g.Hashish

1986, 1988), and have suggested that US is ineffective anti-inflammatory tool.

The pain relief following US therapy may

be due to changes in pain perception mediated by circulating opiates. Exposure to US application enhances the release of substance Pfrom the nerve fibers, which induce analgesia and increased pain threshold by desensitizing the nociceptors.29 Furthermore, animal study demonstrated that US can reduce the sodium­ potassium ATPase pump activity, which if occurred in the neuronal  plasma membrane, might inhibit the transduction of noxious stimuli and subsequent neural transmission, which may account in part for pain relief, which is often experienced following clinical exposure to therapeutic US .

The results of the current study are in constant  with the findings  of Rubin  et al.l2 who reported significant reduction in facial swelling  and  bruising  after  application  of US in patients undergoing surgical cosmetic procedures. These results are supported by Van der Windt et al.5 who stated that ultrasound is currently used in physical therapy to reduce swelling, improve immobility and treat joint mJunes.

Hashish et al.,  in his double  blind study

revealed that, US (0.1-1.5W/cm2) induced reduction  in  facial  swelling  and  pain  after oral surgery.30  Recently, Berna-Serna et al., reported significant reduction of rectus sheet hematoma, with associated relief of pain after US application (1MHz, 1.5W/ cm2) for 8 to 12 minutes.31 The difference between this study and our study is in regards to the frequency of US (lMHz versus 3MHS) due to deep and superficial location of hematoma between the two studies.

Our study has several limitations. Because it was designed to assess both safety and efficacy,  and   because,  to  our   knowledge, it  was  the  first  ultrasound   study  on  live patients who were treated immediately  after facial aesthetic surgeries. We used modest treatment parameters (intensity, pulsing and time) to make the benefit of US as efficient as possible to earliest repair phase, and thus have a  promotional  effect  on  the  whole  healing

cascade.  However,  it is  possible  and likely that efficacy was not optimized. Therefore, more optimized exposure parameters (eg, continuous   mode  of  US  higher   intensity,

1MHz)  may  have  induced   greater  effects. The small number of patients does not allow any definitive statement to be made regarding the efficacy of US therapy in accelerating recovery in patients following facial aesthetic surgeries,  and  the  statistical   power  of  the study  is  low.  However,  all  subjects   were treated  in exactly  the  same way  and at the same parameters.

In conclusion, we reported the safety and

efficacy of the therapeutic US in expediting resolution  of  ecchymosis,  edema  and reduction   of  postoperative   pain  following facial aesthetic surgeries. The results of the study   would   encourage   plastic   surgeons and therapists to use the US as a valuable postoperative tool to accelerate resolution of ecchymosis, edema, and pain.

References:

1- DeFatta, RJ, Krishna S, Williams EF: Pulsed-Dye Laser for treating ecchymosis after facial cosmetic procedures. Arch Facial Plast Surg 2009; 11(2): 99-103.

2- RubinA: Treating of postoperative bruisiing and edema with external ultrasound and manual lymphatic drainage. Plas Reconstr Surg 2002; 109: 1469-1471.

3- Shah SGS, FarrowA, Esnouf A: Availability and use of electrotherapy  devices: A survey. International Journal of Therapy and Rehabilitation  2007; 14(6): 260-264.

4- Warden SJ, McMeeken JM: Ultrasound usage and dosage in sports physiotherapy. Ultrasound   in  Medicine    and   Biology

2002; 28(8): 1075-1080.

5- Dyson M: Mechanisms involved in therapeutic     ultrasound.    Physiotherapy

1987; 73: 116-120.

6- Kitchen SS, Partridge CJ: A review of therapeutic            ultrasound.    Physiotherapy

1990; 76: 593-600.

7-   Hadjiargyrou    M,   McLeod   K,  Ryaby JP, Rubin C: Enhancement of fracture healing by low intensity ultrasound. Clin

Orthop1998; 355(suppl):  216-229.

8- Vander Windt DA, van der Heijden GJ, van der Berg SG, et al: Ultrasound therapy for musculoskeletal  disorders: A systematic review. Pain1999; 81: 257-271.

9- Speed CA: Therapeutic ultrasound in soft

tissue  lesions.  Rheumatology   2001;  40:

1331-1336.

10-Baker   KG,   Robertson   VJ,   Duck   FA: A review of therapeutic ultrasound: Biophysical effects. Phys Ther 2001; 81:

1351-1358.

11- VanderHeijdenGJ, vanderWindtDA, Van der Winter AF: Physiotherapy for patients with soft tissue shoulder disorders: A systematic  review  of  randomized  trials. BMJ 1997; 315: 25-30.

12-Robertson  VJ, Baker KG: A review of therapeutic     ultrasound:     Effectiveness studies. Phys Ther 2001; 81: 1339-1350.

10-Dixon JS, Bird HA: Reproducibility along a 10  em vertical  visual  analogue  scale. Ann Rheum Dis 1981; 40: 87-89.

11-Sabagh RM, Ali A, Taher MO: Role of ultrasound in minimizing the postoperative swelling and pain after cosmetic facial surgery.  Sc J Az  Med  Fac(Girls)  2006;

27(2): 1877-1886.

12-Piso  DU,  Eckardt A,  Schafer P, Gehrke A: Early   rehabilitation    of   head-neck edema after curative surgery for orofacial tumors. Am J Phys Med Rehabil2001; 80:

261-269.

13-Dyson  M, Pond JB, Joseph  J, et al: The stimulation   of   tissue   regeneration   by means of ultrasound. Clin Scil  968; 32(2):

273-285.

14-Dyson    M,    Franks    C,    Suckling    J: Stimulation  of healing of varicose ulcers by  ultrasound.   Ultrasonic   1976;  14(5):

232-236.

15-Paul  BJ,  Lafrotto  CW,  Dawson  AR,  et al: Use of ultrasound in treatment of pressure sores in patients with spinal cord injury. Arch Phys Med Rehabil 1969; 41:

438-440.

16-Webster DE, Pond JB, Dyson M, Harvey W: The role of cavitation  in the  in vitro stimulation  of protein synthesis in human fibroblasts by   ultrasound.    Ultrasound

Med Biol1978; 4(4): 343-351.

17-Webster DE, Harvey W, Dyson M, Pond JB: The role of ultrasound- induced cavitation  in the 'in  vitro' stimulation  of collagen synthesis in human fibroblasts. Ultrasonics  1980; 18: 33-37.

18-Dinnot M, Young S, Crumt A: The significance of membrane changes in the safe and effective use of therapeutic  and diagnostic   ultrasound.   Phys  Med   Biol

1989; 34(11): 1543-1552.

19-Mortimer AJ,  Dyson M: The effect of therapeutic  ultrasound on calcium uptake in fibroblasts. Ultrasound Med Biol 1988;

14(6): 499-506.

20-Ryaby J, et al: Low intensity pulsed ultrasoundincreasescalciumincorporation in both differentiating  cartilage and bone cell cultures. Trans Orthop Res Soc 1989;

14:

21-Dyson     M:    Therapeutic     applications of         ultrasound.   In:   Biological    effects of         ultrasound.    Churchill    Livingstone (Publisher); 1985; p.135-155.

22-Fyfe M, Chahl L: Mast cell degranulation: a possible mechanism of action of therapeutic  ultrasound.  Ultrasound  Med Biol 1982; 8(Suppl): 62-65.

23-Fyfe M,  Chahl L: Mast cell degranulation and       increased    vascular    permeability induced by 'therapeutic' ultrasound in the rat ankle joint. Br J Exp Pathol 1984; 65 (6): 671-676.

24-Dyson   M,  Luke  D:  Induction  of  mast

cell degranulation in skin by ultrasound, ultrasonics, ferroelectrics and frequency control.  IEEE Transactions  1986;  33(2):

194-201.

25-Young S, Dyson M: Macrophage responsiveness  to therapeutic  ultrasound. Ultrasound   Med       Biol   1990;   16(8):

809-816.

26-Devcic-Kuhar B, Pfaffenberger S, Groschl M, et al: In vitro thrombolysis  enhanced by   standing   and  travelling   ultrasound wave fields. Ultrasound Med  Biol 2002;

28: 1181-1187.

27-Francis CW, Onundarson  PT, Carstensen EL, et al: Enhancement  of fibrinolysis in vitro by  ultrasound. J Clin Invest  1992;