The aim of the publication is to render information to neurologists, urologists and family doctors about the latest achievement in sedation of skeletal pains and the treatment with streptokinase (SK). Chlamydial infection is the basic etilogical factor in patients with spondylosis of urogenital origin and spondylarthrosis.

The urologist of St.Petersburg were the first to diagnose the localization of lumbar-sacral pains in 40,2% of chronic prostatitis patients in 1989. The study was published and the was considered to be related to a secondary lumbar-sacral radiculitis which was the prostatitis complication but not the basic disease. Pathogenetic relationship of lumbar-sacral pain syndrome was diagnosed in 58,2% of prostatitis patients. The prevalence of these complications depended on the stage of chronic prostatitis and the translocation of the infection (4).

During 20 years, 1097 patients, aged from 13 to 80 yrs., were receiving the enzyme therapy with streptokinase at the Urology Department No.11 of Riga Clinical Hospital "Gailezers". From 32% patients with chronic prostatitis, paraprostatitis and urogenital venous plexus inflammation complained of pains in the nape, spinal thorax and lumbar area.

As a result of etiopathogenetic sanation, the spinal pain syndrome regressed. Almost 10% of patients who did not have complaints of urogenital character, but experienced skeletal pain syndrome, were diagnosed urogenital chlamydiosis and spondylosis of urogenital origin on examination, as well as spondylarthrosis with a secondary skeletal pain syndrome. When treating chronic chlamydial prostatitis, paraprostatitis and urogenital venous plexus inflammation, the skeletal pain syndrome regressed.

Clinical Case 1.

A patient A., 35 yrs.old, was treated at the Urology Department for 58 days (Case history Nr.4032-01). On admission the patient did not have any urogenital complaints. No complaints had been observed earlier as well . As a result, while treating the patient for spinal spondylosis and nerve roots pain syndrome neither the family doctor nor the neurologists diagnosed the basic disease - Chlamydia trachomatis induced prostatitis, paraprostatitis, urogenital venous plexus inflammation,etc., administering only symptomatic analgetic therapy instead of etiopathogenetic treatment. Therefore, the basic diagnosis was incorrect and the treatment - inadequate. After 2 year-long ineffective treatment, indicated by neurologists, the disease progressed and the patient experienced pains in the lower extremities. The patient was consulted by Dr. Katlaps, Head of Surgical Department, while examining the patient per rectum, prostatitis was diagnosed. At the Urological Department, Chlamydia trachomatis infectious prostatitis with multiple complications was diagnosed. Using DIM (direct immunofluorescence method) with monoclonal antibodies, Chlamydial antigen structures were verified (+).

Under IIM (indirect immunofluorescence method) - Chlamydia trachomatis antibodies in blood (2+) in titre 1:16.

Clinical diagnosis:
1) Urogenital chlamydiosis
2) Chronic chlamydial prostatitis
3) Paraprostatitis
4) Calcinosis of the prostate
5) Inflammation of urogenital venous plexus
6) Phlebothrombosis of the small pelvis
7) Varicose veins of both legs along v.saphena magna and edema of the shank
8) Secondary hypercoagulaemia
9) Reactive chlamydial polyarthritis
10) Spinal spondylosis of urogenital origin and spondylarthrosis with skeletal pain syndrome

The patient was diagnosed the inflammation of spinal vertebrae,i.e. spondylosis due to chlamydial infection and intravertebral joint polyarthritis - spondylarthrosis.
Conclusion made by a neurologist: cervical, thoracic and lumbar spondylosis with skeletal pain syndrome.

USS gl.prostatae:
Prostate AP - 2,5 cm, CC - 3,0 cm, LL - 4,7 cm with calcinates in the parenchyma suggesting chronic prostatitis in the III-IV inflammatory phase.

Roentgenologist's conclusion:
deformative spondylosis at vv C III - C VII level. Signs of deformative spondylosis at vv Th VIII - Th IX level. No changes are observed either in the form or the structure of lumbar vertebrae.
Characteristic values of coagulogram demonstrate a marked hypercoagulaemia (Table 1).
Due to the inflammation of urogenital venous plexus, phlebothrombosis of the small pelvis and hypercoagulaemia, the patient was indicated an enzyme therapy course with streptokinase (SK), heparin and antichlamydial antibiotics.

In the period of 58 days of the enzyme therapy , the patient was receiving streptokinase in the doses of 15 000 - 350 000 e.u. i/v, in total 13 500 000 e.u. i/v. No larger doses were allowed, since the antistreptase titre grew up very fast, reaching 1 800 a.u. 1 ml plasma, and when SK dose reached 350 000 e.u., arthralgias and chest pain syndrome increased. Continuing the enzyme therapy with SK in the doses from 150 000 - 200 000 e.u., the allergic reactions disappeared.

Alongside with SK and heparin, the patient was receiving antichlamydial antibiotics: doxicycline, sol. Metrogil 0,5% 100 ml i/v (due to paraprostatitis), gentamycine, erythromycine, cephazol, ciprinol i/v, "A" and "E" vitamins in capsules, physical procedures and the massage of the prostate 2 times a week.

SK antibody elimination from 1 800 to 1 300 a.u. in 1 ml plasma was the evidence of a positive sanogenous reaction. The skeletal pain syndrome gradually regressed. There was no need for the analgetics, such as diclophenax, ibuprofen and xefo-lornoxicam.

The patient is cured now. To avoid the reinfection, it is necessary to treat the patient's spouse, who feels well but is a carrier of Chlamydia trachomatis infection.

Etipathogenesis and differential diagnosis of the skeletal pain syndrome has been studied for quite many years. However, being a diseases hard to treat in practice, it has been undeservedly forgotten [1.-4.]. Sedation of secondary skeletal pain syndrome of urogenital origin and its treatment with streptokinase is associated with the possibilities of fibrosis and sclerosis processes to regress in long and intravertebral ligaments of the spine.

Morphological studies have shown that fibrosis develops after chronic productive (proliferative) infectious inflammation. Sclerosis may be labile or reversible, it does not progress after prevention of the pathogenic factor's activity [5]. The inflammation is the usual cause of fibrosis.Timely and correctly cured inflammation is the basic prevention of fibrosis and sclerosis, thus avoiding the factors which may cause the damage of the organ cell parenchyme. To some extent, the very process of fibrosis is reversible, if only the inflammation is timely controlled [6].

Regression of the prostate as well as spinal fibrosis and sclerosis processes can be achieved by administering proteolytic, fibrinolytic enzymes and their activators: streptokinase, urokinase and the tissue plasminogen activators (t-PA) [7,8,9,10,11,12].

SK pharmakokynetic properties are not equal at different inflammatory stages. In prostatitis patients, SK has antiinflammatory properties in 2,3,4 inflammatory stages. SK guarantees the regression of the inflammation of urogenital venous plexus and improves the microcirculation. SK stops the proliferation of the connective tissues and stimulates the reparative regeneration of the smooth muscle of the prostate. SK possesses hepatoprotective properties. SK is the inductor, eliminating the antibodies and the antigen structure of intracellular chlamydial infections. It has immunomodulator's properties as well.

The chief proteolytic enzyme in the human blood and tissues is plasmin - fibrinolyzin, which is also a proteinase (3.4.4.14.). There is no deficit of proenzyme - plasminogen in the patient's blood and tissues, but it is not activated due to the inhibitors' influence.

Such inflammatory processes of the small pelvic organs as prostatitis, paraprostatitis, the inflammation of urogenital venous plexus, the phlebothrombosis of the small pelvis and the inhibition of plasminogen activators may cause some secondary complications [13]. The inflammation of urogenital origin (Chlamydia trachomatis) spreads in the way of translocation, through veins and lymph. The inflammation of the small pelvis spreads (is metastasing) along the spinal vertebrae and paravertebral venous plexus, that connects the pelvic bone venous plexus up to the cranium [1.-2.].

In cases of paraprostatitis, the urogenital venous plexus with its multiple anastamoses with spinal veins is the basis for the pathogenesis of the skeletal pain syndrome, thus providing the translocation of chlamydial infection into the spinal intervertebral articulations. Venous stasis with the accompanying exudative inflammatory phase produces the intervertebral disc and ligament edema which is manifest in the form of skeletal pain syndrome and is diagnosed as spondylosis with a fibrous process in the vertebral column.

 

Table 1: Coagulogram

Conclusion:
ASK titre dynamics - 200 - 800 - 1 200 - 1 800 - 1 800 - 1 400 - 1 400 - 1 600 - 1 600.
The patient has a positive sanogenous reaction, it suggests a good prognosis.
Due to dyscoagulaemia (10.04.2001) and an increased ASK titre, an antirelapse enzyme therapy course is being planned in 3-5 months.

Clinical case 2.

A patient M., 70 yrs. old (Case history Nr.4032-01), with a chronic recurrent prostatitis, paraprostatitis, deformative spondylosis of the spinal lumbar vertebrae and the skeletal pain syndrome, has been ill for more than 15 years. He had repeatedly ( 8 times) received the enzyme therapy course with streptokinase and antichlamydial antibiotics. The normalization of coagulogramm- indicating values was always achieved, but not the hypocoagulaemia. Remission periods lasted for about 1-2 years. After the last 1 year-long remission period, a relapse (or reinfection) occurred. He was hospitalized because of the complaints of pains in the lower part of the abdomen along the midline above the symphysis, frequent urination of weak spurt, pain in the groin, perineum, spinal lumbar region and headaches. On physical load - dyspnea and the pain the the cardiac area. Nervousness, erectile dysfunction, poor sleep.

Diagnosis:
1) Postinfectious prostatitis (chlamydial)
2) Paraprostatitis
3) Inflammation of urogenital venous plexus
4) Deformative spondylosis vL1 - vL2 - vL3 with neoarthosis
5) The skeletal pain syndrome
6) Calculous cholecystitis (etc. co-diseases)

Roentgenogram vv lumbales was performed in 2 projections:
Physiological lordosis is preserved with a slight scolisosis to the right. The intervertebral spaces are of normal width. On the left side between vL1 - vL2 - vL3 there are massive spodylophytes with neoarthrosis.

The patient was receiving the enzyme therapy course for 30 days with streptokinase, the dose was 5 000 - 500 000 e.u. On the 12th enzyme therapy day, after SK 3 750 000 e.u., the patient developed bleeding from the the injection sites and there appeared hematomas subcutaneously.
The coagulogram showed a marked hypocoagulaemia with a spontanous fibrinolysis 58% and hypofibrinolysis 0,88 g/l.

Further on SK dose was decreased up to 5 000 e.u., which provided the activation of the fibrinolytic enzyme system at the level of hypocoagulaemic threshold (Table 2). Starting with the 22nd enzyme therapy day, SK dose got gradually increased up to 250 000 e.u. per day, providing a spontaneous fibrinolytic activity at the level of hypocoagulaemic level.

During 30 days of the enzyme therapy, the patient received 4 950 000 e.u. of streptokinase. Prostatitis, paraprostatitis and the inflammation of urogenital venous plexus regressed and only then the regression of the skeletal pain syndrome was seen to begin.

One should mention, that within the previous enzyme therapy course, lasting for 28 days (Case history Nr. 6528-00), the patient had received in total SK - 4 750 000 e.u., hypocoagulaemia, however, was not achieved.

During the last enzyme therapy course, fibrinolysis with subcutaneous hematomas and bleeding from the injection sites, was seen on the 12th day, but it was stabilized at the level of hypocoagulaemic threshold when decreasing SK dose.

 

Table 2: Coagulogram

Conclusion:
On the 12th enzyme therapy day, there has been achieved a marked hypocoagulaemia with bleedin in the injection sites and subcutaneous hematomas. Therapy: Streptokinase without Heparin - for 7 days - only 5 000 u. (i/v). Hematomas got absorbed, bleeding stopped.

Conclusions:

• With each repeated anti-relapsing enzyme therapy course, even after 1-2 years long remission period, SK doses decrease, but the activation of the fibrinolytic enzyme system - increases. Allergic and anaphylactic reactions to antigen SK decrease or completely disappear.
  For the treatment of spinal intervetebral and long ligament fibrosis, sclerosis and deformative spondylosis with SK, it is obligatory to ensure individually a long-controllable hypocoagulaemia for at least 2-3 weeks.

• It is a new achievement in sedation of the skeletal pain syndrome in patients with chlamydial paraprostatitis, spinal spondylarthroses of urogenital origin, i.e. in the enzyme therapy with SK to control fibrosis and sclerosis processes.

• The pain in such areas as the nape, the spine, the sacrum, radiculitis and the skeletal pain syndrome is the complication of the basic disease, a secondary phenomenon. The cause of the pain syndrome should be looked for in the small pelvis and can be often diagnosed by palpation, examining per rectum. Family doctors and neurologists not always examine their patients with backaches and the skeletal pain syndrome per rectum, as a result the etipathogenetic diagnosis is not made. These patients receive symptomatic anti-pain therapy instead of etiopathogenetic treatment. Subjective findings and the localization of the pain may be variable, which is commonly the basis for diagnostic errors. Patients who do not have urogenital complaints, but have the signs of the skeletal pain syndrome, if not examined per rectum, may not be diagnosed spondylosis or spondylarthrosis of urogenital origin, and, as a result, an inadequate, symptomatic therapy is indicated. Specific signs of the pain syndrome for one and the same patient at various periods of time depend on the stage of the inflammation and the translocation of the infection in the adjacent organs, etc. (Clinical case 3).

Clinical Case 3.

A patient D., 53 yrs.old (Case history Nr.121-01) is suffering from chronic prostatitis and sarcoidosis for more than 16 years. He was treated at the tuberculosis clinic "Sauriesi" and 5 times at the Urology Department of Riga Hospital No.7. He has repeatedly received the enzyme therapy with SK and antichlamydial antibiotics. The patient's spouse feels well but is a carrier of a latent chlamydial infection and the source of her husband's reinfection. The duration of the last remission period was 3 years. On admission, the patient complained of great tiredness and weakness all day and night [15]. He mentioned the pain in the nape, in the lumbar region, the sacrum and the knee joints. Lymph nodes were enlarged in the groin and in the hollow of the knee. No urological complaints were mentioned!

Roentgenogram of vertebrae lumbales:
Scoliosis to the right. Lateral osteophytes vv L2 -L3 on the left side. Slight anterior osteophytes at vvL4 - L5 -S1 level.

Roentgenologist's conclusion:
Deformative spondylosis at L1 - S1 level.

Neurologist's conclusion:
The skeletal pain syndrome due to deformative spondylosis in the lumbar and sacral regions.

Indicators of hypercoagulaemia prior to the enzyme therapy were: blood coagulation time - 8', caolin time 65", fibrinogen B - (++), spontaneous fibrinolysis 4%, fibrinolysis of plasma euglobulin fraction - 240', proteolytic resistance 160 u.

Clinical diagnosis:
1) Exacerbation of chronic prostatitis
2) Inguinal lymphadenitis
3) Dyscoagulaemia with a tendency to hypercoagulaemia
4) Deformative spondylosis at vvL1 - L5 - S1 level
5) The skeletal pain syndrome
6) Chronic fatigue syndrome

In the Urological Department the patient received the enzyme antibiotic therapy with (SK) streptokinase for 52 days - 25 000 - 650 000 e.u. per day i/v - 52 days, the course - 22 750 000 e.u. Due to the increase of arthralgias, greater doses of SK were not given. With the development of hypercoagulaemia, heparin was indicated 5 000 u i/v 1x a day, 52 days. Simultaneously the patient was receiving antichlamydial antibiotics, vitamin E, body massage and physical procedures.

As a result of the enzyme antibiotic therapy, the inflammatory processes in the prostate and lymphadenitis regressed completely within 30 days, but 52 days were needed to treat the skeletal pain syndrome.

Remission phase was achieved and stable sedation with SK without the use of analgetics. Up to the end of the enzyme therapy course, the activation of the fibrinolytic enzyme system was maintained at the level of hypocoagulation threshold:
- blood coagulation time - 17'
- caolin time - 85"
- thrombin time - 23"
- APTL - 48,4"
- spontaneous fibrinolysis - 17,5%
- fibrinolysis of plasma euglobulin fraction - 110'
- fibrinolysis depending on XII factor - 3'40"
- proteolytic resistance - 140 u.

Dynamics of antistreptase titre - 100 a.u. - 400 - 800 - 1 000 - 1 600 - 1 200 - 1 200 a.u. proved the beginning of a long-term remission phase.
SK antibodies reached the level of 1 600 a.u. of 1 ml plasma with the following unduction blockage and the elimination start of 1 200 a.u. (Table 3).

Both the skeletal pain syndrome and chronic fatigue syndrome regressed.
The patient works as a fireman. His working abilities have been restored.

 

CONCLUSIONS:

1) A new achievement has been found in sedation of patients having the skeletal pain syndrome of urogenital origin due to chlamydial infection resulting in spoldylosis and spondylarthrosis;

2) The enzyme therapy with SK is the basis for sedation of the skeletal pain syndrome;

3) One can achieve the regression of fibrosis and sclerosis of the spinal vertebrae by using a complex of proteolytic, fibrinolytic enzymes and their activators: streptokinase, urokinase and tissue plasminogen activator (t-PA);

4) The regression of spondylosis, spondylarthrosis and the skeletal pain syndrome does not occur at hypocoagulaemia of short duration, lasting only for some days. Patients, treated by SK, should have 15-30 days-long activation of fibrinolytic enzyme system at the level of hypocoagulaemic threshold;

5) For prevention of hemorrhagic complications which may develop during the enzyme therapy, one should provide a constant blood coagulation system control just in the ward before and after the intravenous enzyme infusion;

6) Etipathogenesis of polyarthritis and spondylarthrosis of urogenital chlamydial origin is similar. The inflammation of intervertebral articulations of the spine is, in fact, polyarthritis as well. The patient may have polyarthritis of the extremities and the spinal vertebrae simultaneously [14];

7) To sedate the skeletal pain syndrome and to achieve the regression of the fibrous processes, it calls for even 2-3 enzyme therapy courses.

8) It is important to attain the blockage of SK antibody genesis, induction and synthesis with the further SK antibody elimination up to 50-150 a.u. level in 1 ml plasma [16]

9) Optimal elimination of streptokinase has to take place during the remission;

10) As a result of the blockage of SK antibody synthesis, the patient's immune system loses the ability to recognize an alien antigen, i.e. streptokinase, and during a repeated enzyme therapy course, it does not respond to it. Only now, when treating by SK, no antibodies are formed and one can hope for the sedation of the skeletal pain syndrome;

11) As a result, relatively small doses of SK yield a quick fibrinolytic activation effect. Sanogenous reaction is manifest in a long-lasting sedation of the skeletal pain syndrome;

12) Spondylites of urogenital origin, as well as spondylarthroses and the skeletal pain syndrome are the complications of paraprostatitis, but not the basic disease. The patient should be treated at the urologist's who is competent in the enzyme therapy.

List of Literature:

1. Batson O.V. "The role of the vertebral veins in metastatic processes."
   Annals of Internal Med., 1942, v.16, Nr.1

2. N.V.Kurenoi, "Kliniceskoje znacenije mocepolovogo spletenija"
   Str. 51-52, "Zdorov'ja", Kiev - 1968.

3. P.Ivdra, E.Smiltēns "Classification of chronic prostatitis following syndromes of affection"
   I Conference of Surgeons-Urologists of Baltic Republics in Riga, October 10-12,1973,
   261.-264., 266.-268., 270.-271.pp

4. V.N.Tkacuk, A.G.Gorbachov, L.I.Agulanskij. "Simptomatika i osobennostji klinicheskogo
   lechenija hronicheskogo prostatita", str.78-83, V kn."Hronicheskij prostatit". Medicina, 1989

5. R. Kleina, "Sklerozes morfologiskie aspekti dazados organos".
   Zurnals "Enzimterapija", Nr.2, 2000., 32.lpp.

6. I. Taivans, "Fibrozes patofiziologiskie mehanismi".
   Zurnals "Enzimterapija", Nr.2, 2000., 32.lpp.

7. P.Ivdra
   "Chroniska prostatita enzimterapijas indikacijas un antibiotiku rezistences regresijas iespajas".
   Zurnals "Latvijas Arsts", 1994., 2: 120-122.

8. P.Ivdra
   "Urokinaze antibiotikrezistentas urogenitalas chlamidiozes arstesana".
   Zurnals "Latvijas Arstu zurnals", 1995; 3: 30-35.

9. P.Ivdra
   "Indikacijas chlamidiju izraisita prostatita enzimterapijai".
   Latvijas Arstu zurnals, 1998; junijs: 16020.

10. P.Ivdra, E.Platkajis, I.Geldners,
    "Indications for enzyme therapy with streptase, urokinase and tissue plasminogen activator - t-PA in chlamydial prostatitis", 1998, http://www.expo.lv/gailes/prostatitis.htm

11. E.Platkajis, P.Ivdra, A.Miltins, I.Geldners, I.Ancupane.
    "Clinical value of dynamics of streptokinase antibody level in antibiotic resistant chlamydial prostaitis patients during enzyme therapy with streptokinase", 1999, http://www.expo.lv/gailes/streptokinase.htm

12. P.Ivdra , A.Zilevica, A.Miltins, I.Ancupane
    "Role of tissue plasminogen activator (t-PA) in enzyme therapy of antibiotic-resistant chlamydial prostatitis".
    1999, http://www.expo.lv/gailes/actilyse_prostatitis.htm

13. P.Ivdra, G.Purmalis, A.Zilevica, I.Geldners, J.Zalkalns, I.Ancupane, A.Miltins.
    "Streptokinase as plasminogen activation inhibitor for chlamydial prostatitis patients".
    2000, http://www.expo.lv/gailes/streptokinase.htm

14. P.Ivdra, A.Zilevica, A.Miltins, I.Ancupane, I.Geldners.
    "Chlamydial Polyarthritis. Possibilities of enzyme therapy with streptokinase and plasminogen activator (t-PA) in chlamydial polyarthritis of urogenital origin", http://www.expo.lv/gailes/polyarthritis.htm

15. A.Zilevica, P.Ivdra, J.Zalkalns, I.Ancupane, E.Baumanis
    "Chronic fatigue syndrome, fibromyalgia, enzyme therapy of chronic fatigue syndrome, fibromyalgia enzyme therapy with streptokinase, urokinase and tissue plasminogen activator (t-PA) for patients with antibiotic-resistant systemic chlamydial infections", 2001,. http://www.expo.lv/gailes/fibromyalgia.htm .

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• PROTEINASES IN ENZYME THERAPY OF CHRONIC PROSTATITIS
• TREATMENT OF CHLAMYDIAL SPONDYLITIS
• STREPTOKINASE IN GERONTOLOGY
• SPECIFICITY OF ENZYME THERAPY IN TREATMENT OF LATE INFLAMMATORY FORMS OF PROSTATITIS
• POSSIBILITIES OF ENZYME THERAPY IN PAIN SYNDROME
• CHRONIC FATIGUE SYNDROME, FIBROMYALGIA ENZYME THERAPY
• ENZYME THERAPY OF ANTIBIOTIC-RESISTANT AND UROGENITAL CHLAMYDIOSIS
• STREPTOKINASE AS PLASMINOGEN ACTIVATION
• VIAGRA IN PROSTATITIS TREATMENT 
• ENZYME THERAPY WITH STREPTOKINASE
• CHLAMYDIAL PROSTATITIS
• ACTILYSE IN PROSTATITIS TREATMENT
• ENZYME THERAPY IN CHLAMYDIAL POLYARTHRITIS
• MEN PATHOLOGICAL CLIMACTERIC