Copyright 2007 R. Klimek

"Prevention, Diagnosis and ACTH-Depot Therapy of Obstetrical Complications with Cancerous Risk"

Rudolf Klimek, Marek Klimek, Dariusz Jasiczek

Introduction
Cervical cancer
Diagnosis of fetal maturity
Hormonal and enzymatic monitoring of obstetrical therapy
Causal obstetrical prevention of cancer
References


Introduction

A meta-analysis of many medical papers showed in the last few decades an increase of cancer and no decrease in perinatal mortality or serious neonatal morbidity following delivery between 34 and 37 weeks of gestation in both developed and developing countries [7,8]. The diagnosis of human cancer is always accompanied by the strong feeling of fear, which results from the common image of the disease as being devastating and fatal in character. This is mainly caused by the fact that the society is not adequately informed about reasons and conditions of neoplastic diseases.

A multicellular organism, as well as each individual cell, has to exchange matter, energy and information with its closest environment, which is the subject of psycho-neurocybernetics [29,30]. An intrinsic quality of human ageing is the loss of strength and well-being, what defined as thermodynamic entropy also occurs in other natural phenomena. The more disorganised the system (e.g. organism, cell, nucleus or just cell cytoplasm) is, the greater the losses are. If, for any reason, the cell reduces the production of its own entropy, it must in turn increase entropy in its environment to remain alive, by means of broadly understood dissipation of matter and/or energy. Such excessive dissipation of matter and energy by neoplasms (new systems) in the organism (environment) explains the more and more devastating character of subsequent conditions and disease symptoms. This characteristic feature of cancer appears rapidly in the new dissipative form of cell life. A neoplastic cell is formed in replacement of and out of cells, as a direct consequence of self-organising pre-cancer cells, whose further existence is disabled by extreme impairment of their metabolism [16,18-21].

Do góry

Cervical cancer

The best understood human neoplasm is cervical cancer, which is called mothers' disease or the disease of early sexual initiation, which reflects its wide social impact [22-24]. There are common thermodynamic roots of cervical intraepithelial neoplasia (CIN), cervical cancer and premature delivery. They can be promoted not only by many non-specific life-style factors (maternal age, socioeconomic status, educational level, amount of prenatal care, alcohol consumption, cigarette smoking, unmarried state during pregnancy), but also owing to e.g. faulty prediction and determination of birth data, instrumental instead of possible natural labor, infrequent diagnosis and wrong therapy of hypothalamic conditioned miscarriages et cetera.[12,25,29]

The life of human zygote begins at the moment of union of two live reproductive cells, which separately are deprived of the most important feature of cellular life forms, i.e. the ability to divide into daughter cells. Only thus formed hybrid cell is able to divide into three kinds of cells (I-III), whose further division leads to development of mature human beings (I somatic cells), in whom individual reproductive cells (II) will develop, as well as temporary cell structures (III) just for the period of pregnancy (placenta, fetal membranes) [24,25]. Each of the three cell types is subject to thermodynamic laws, as all biological systems. Physiologically, the life of an individual cell ends with its division into two cells of the same genetic type or as a result of dematerialization during apoptosis, i.e. programmed transformation of its matter into energy needed for formation of multicellular structures, e.g. embryo or placenta.

Life itself is more important than containing it the existing form of cells, since instead of necrosis or apoptosis, the cellular system in an unfavourable environment can, and sometimes even must self-organize into new cellular structures to prolong their own existence by dissipation of matter, energy and information in the nearest biological surrounding. Therefore, a neoplasm as a dissipative structure begins its existence at the end of the life of a dissipathogenic cell. Each neoplastic disease possesses a variety of forms as well as a unique identity of the neoplasm as its own sufficing cause. This needs for an early detection, as well as an etiological treatment of pre-neoplastic states which can be ever more precisely detected with new methods based on psychoneuroimmunology. For example, cryosurgery, laser therapy or radical electrocautery are all effective in eradicating cervical cancer, but not the dissipathogenic state (cancerogenic) of uterine cells. Consequently this local ablative therapy must be followed by medical restoration of the body’s defense mechanism to prevent the recurrence of the disease. Only neuro-immunotherapy as a mean of treating the whole body can alone prevent and cure the dissipathogenic states, as a final causes of cancerogenesis of any part of the body, not only the uterine cervix. Also primary prophylaxis of neoplasms requires that not only the dissipathogenic state of cells be prevented, but also their tissue surrounding be normalized to head off the risk of the self-organization of neoplastic forms of life [11,17,34,35].

Neither viruses, nor many other microorganisms can be classified as factors sufficient for the neogenesis. Their complete elimination, even as necessary factors of infectious diseases can only reduce the incidence of dissipathogenic cells. Infected cells or infectiously changed tissues in their final phase of existence are often recognized as a precancerous state, but their genome does not differ from other organism cells, and that is why the carcinogenesis can still be prevented by direct fighting of pathogenic microorganisms, and indirectly by strengthening the body by neurohormonal therapy or vaccine immunopotentialization. For example saprophytic bacteria of the Lactobacillus vaginalis type cooperate with the organism in the direct fighting of infectious microorganisms, whose antigens they recognize. The introduction of the vaccine comprising coccoidal and weakened forms of Lactobacillus vaginalis leads to the significant reduction in the inflammatory state rates and concurrently increases the number of saprophytic Lactobacillus vaginalis bacteria in women treated for infertility, in whom intraepithelial neoplasia and/or non-specific vaginitis was found [1,2,27].

Do góry

Diagnosis of fetal maturity

Cervical cancer can be not only prevented, but also effectively treated in spite of increased incidence in women due to the growing number of operative deliveries and inadequate use of steroid preparations. It should be noted that the same factors remain in a cause-and-effect relationship with the occurrence of premature deliveries, e.g. about 20% of women with post-partum neurohormonal disorders have clinically recognizable precancerous states of cervix due to, among others, obstetrical haemorrhages, miscarriages and first of all premature deliveries of child [21,35]. Unfortunately, the state of the newborn is assessed solely by the Apgar scale, originally intended to scoring of post-partum breathing adaptation, but it should be described with the number of its technical quanta using six easily identifiable morphologically-functional features of the newborn, what can be done even by the mother herself [31]. More importantly, the level of fetal maturity can be predicted already a few weeks before birth, using standard ultrasonographic equipment with appropriate software [7,12,16,21]. Only a state of maturity given in the form of technical quanta is useful in determining the full maturity of the fetus, equaling the proper date of birth determined by the simultaneous disappearance of pregnancy tolerance on the side of the mother. Statistically determined date of birth cannot be used to determine the actual birth date, just as the Apgar scale cannot determine the future health of the children, especially those born operatively. There is no reason for cesarean sections and inductions of labor in more than 15% of all pregnancies, whatever connected with increased hemorrhage, premature birth and post-pregnancy neuro-hormonal disturbances as well as an increased risk for all neoplastic diseases, not only cancer of the uterine cervix in women with the history of neurohormonal menstruating disorders, chronic and recurrent inflammations of the reproductive organs and long-term hormonal contraception. It requires concurrent adaptation of the nursing, prophylaxis, prevention, diagnostics, treatment and rehabilitation principles to the same level of general knowledge. This, in turn, forces doctors not only to change their opinions, but also to revaluate their professional habits, which proves even more difficult [4,5,21-26,41].

Do góry

Hormonal and enzymatic monitoring of obstetrical therapy

During pregnancy there is increase in the production of hormones and enzymes of the placenta, the function of which has an essential meaning in the mutual mother-fetus neuro-immuno-endocrine relationship [6-9,15,46]. This applies especially to the synthesis and concentration adjustment of isooxytocinases (cystine-beta-aminopeptidase - CAP1 and isocystine-beta-aminopeptidase - CAP2), which decompose hypothalamic hormones [12,14,21]. Any damage to the placenta (partial separation, calcification, vascular clots) or only hypoxia, leads to a decrease of the concentration of these enzymes in the mother’s blood, which automatically results in the increase of not only oxytocin and vasopressin, but also of corticotropin-realising hormone (CRH) and gonadotropin-realising hormone (GnRH). On the basis of the rate of change in the levels of CAP1 and CAP2 in the mother’s blood one can determine when the death of the fetus has – or much more importantly – could occur, or if it is in danger of miscarriage or premature birth [10-14,45,46]. An important part is played also by the endocrine glands themselves, in which the biophysical processes are of great importance, since they are related both to atomic level of metabolism and purely physical blood flow and concentration of its components. At the same time, one may observe underestimation of the dominance of neurohormonal hypothalamus-pituitary-adrenal axis over an analogical axis ended with gonads, which are related to adrenal glands by metabolism of steroid hormones. Excessive use of steroid hormones not only inhibits gonadal steroidogenesis, but also blocks hypothalamic stimulation of endocrine glands, i.e. gonads and adrenal glands. For instance, the use of contraceptive pills for several months excludes a cyclic activity of gonads, whose role is to prepare a potential mother not only to get pregnant but also to a proper development of pregnancy and foetus, e.g. in case of recurrent miscarriages, necessary adrenal stimulation is rarely used. What more, parts of the embryo that remain in the uterus after incomplete abortion are often diagnosed as endometrial polyps, and ovary cysts are not associated with pregnancy-induced increased activity of ovaries that are too long kept on low activity, which leads to unsatisfactory increase of ovary hormone production before their additional synthesis in the placenta.

The above facts may easily be connected with the huge impact of psycho-emotional attitudes of both physicians and patients. However, the treatment of habitual abortions with long-acting adrenocorticotropin (ACTH-depot) gives much better results than steroid hormones, especially their synthetic analogues [9,10,28-30]. Despite repeated and well documented studies no better dosage was found than a one-time therapy between 28. and 34. weeks and twenty four hours before birth, as proposed by G. C. Liggins and R. N. Howie [36]. It is not recommended also in cases of multiple gestations, premature rupture of membranes or fetal and maternal complications (i.e., diabetes hypertension or infection). The mentioned factors do not eliminate the ACTH-depot therapy, which is safe and can be used multiply during all trimesters of pregnancy. What more, a correlation between serial administration of corticotropin and the mass, maturity and the fetal age of the newborn has been repeatedly shown to exist. In effect this proves the superiority of endogenic corticoids over exogenic ones in the prevention of illness and death of the newborn for high-risk pregnancies [10].

A low concentration of ACTH in the mother’s blood decides on the necessity of a substitution ACTH-depot treatment. The fall of ACTH concentration is a natural occurrence only before birth in pregnancies brought to term physiologically, while at an earlier time it signals an endangerment of the pregnancy due to a miscarriage or premature birth. An administration of exogenic ACTH-depot supplements deficiencies and counters an excessive secretion of adrenocorticotropin-realising hormone (CRH), and thus extends the pregnancy. Apart from determining the level of ACTH, it is important to measure the concentration of oxytocinases (CAP1 and CAP2), the syntheses of which increases under the influence of a heightened secretion of hypothalamic hormones during pregnancy.

Indications for the treatment of pregnant women with ardenocoricotropin with a lengthened effect (ACTH-depot) are the following clinical diagnoses: neurohormonal hypothalamic post pregnancy syndrome, habitual miscarriages, a premature childbirth, shortened or non-existent lactation after previous childbirths, long-term usage of anti-conception pills (especially during maturation years), as well as cytologically or colposcopically determined precancerous cervical states. Special group for the treatment are pregnant women who underwent infertility treatment, of which 67% show clinical and laboratory indication for its implementation [34,35].

ACTH dosage applies to intramuscular injection of 0.5 mg ACTH-depot, causing a 32-hour rise in the concentration of adrenal gland hormones in the mother’s blood. In the case of an absence of normalization of the ACTH level in the blood and/or the persistence of clinical symptoms the next dose can be administered already after 48 hours. Usually a single dose in weekly intervals during the first trimester is enough, while the choice of dosage is decided by the clinical development, since the 48-hour effect of a single dose determines the need for sustaining it with a maximum of two following doses in one series. As the pregnancy develops, the almost immediate effect (disappearance of ailment) is sustained for an ever increasing period of time. In the absence of enzymatic monitoring of the pregnancy one may decide on the frequency of injections via the principle of ex juvantibus. Now it is possible to determine the ACTH level in the mother’s blood via laboratory procedure, optimally in the morning, or at any other daily fixed time, for best comparison of the results. Of course a level of ACTH below 5pg/ml is an indication for a continued substitution therapy with ACTH-depot, because the hypothalamic-pituitary-adrenal axis is more significant for the viability of the fetus than the hypothalamic-pituitary-gonad axis. The role of ACTH in creating a tolerance for the embryo becomes apparent in a slight decrease in pre-pregnancy level of this hormone in women with 14.1 ± 7 pg/ml to 12 ± 6 pg/ml and a return to them in the second trimester (15.4 ± 5 pg/ml) to increase in the third trimester to the highest pre-birth levels of 23 ± 10 pg/ml, which, in contrast to oxytocinases, sharply decrease already during delivery [30].

In the course of enzymatic monitoring of hormonal treatment of subsequent pregnancies the levels of both CAP1 and CAP2 are lower than the initial values from previous pregnancies. Levels of CAP1 < 0.8 µmol/l/min and CAP2 < 1.4 µmol/l/min in an early pregnancy are an indication for beginning the therapy with single 0.5 mg doses of ACTH-depot, while levels of both these enzymes ? 4 µmol/l/min in the third trimester require their continued use. A low prenatal concentration of oxytocinases on the order of 3 ± 1 µmol/l/min unambiguously point to an insufficiency in the production of neurohormones, while a substitutive therapy with ACTH-depot causes a normalization of the prenatal concentration of oxytocinases (7.8 and 8.1 µmol/l/min). This especially applies to laboratory monitored pregnancies after fertilization in vitro already from the first weeks of the pregnancy, and not only in those with a significantly low level of ACTH, in which the treatment with this hormone is the method of choice, but also in the case of an absence of an insignificant physiological drop in the level of this hormone, and compulsory with its rising levels in the first trimester instead of only in the third.

The higher is the concentration of CAP1 and CAP2 at the end of the pregnancy, the higher the neurosecretive and immunological capacity of the mother. This is confirmed by the juxtaposition of prenatal levels of these enzymes together with the corresponding increase in fetal age, mass, length, maturity, and the postnatal adaptation of the infant to the values characterizing the infants of the control groups which did not need a substitutive adrenocortical therapy. For example, the application of ACTH-depot results in the disappearance of symptoms of a premature birth without the need for tocolysis and leads to the decrease of breathing disorders in infants. Klimek’s maturity index shows a high positive correlation with fetus age, mass and the length of the infant what was showed by a comparison between the state of the newborn of same fetal maturity when the endangered pregnancy was treated with either ACTH-depot or tocolysis. The use of ACTH-depot statistically lengthens the pregnancy time by 14 days and increases the body mass by 400g in 264 fully mature newborn infants (10-12 K points) while in 69 less mature children (6-12 K points) the pregnancy time extension is 35 days and the mass increases by 1300g. It also eliminates premature delivery in 209 pregnant women with tocolysis where in 46 (23%) of them premature birth has been identified [29,31].

The pregnant patients in need of substitution therapy with a clinical endangered pregnancy miscarried in a whole 80% of cases before the introduction of ACTH-depot therapy in obstetrics 40 years ago [9-13,17]. The best results are obtained in habitual miscarriages due to the hypothalamic insufficiency of the mothers because the damage to the neurosecretory brain cells is permanent, and only the substitutive administration of ACTH is an effective procedure. ACTH-therapy is decisive in high-risk pregnancies, especially so in multifetal ones. The effectiveness of a monitored therapy from the 25th week of pregnancy on is dependant in large measure on the maturity level of each fetus separately. In the case of an uneven rate of growth even when the levels of both CAP1 and CAP2 are correct, it is indicated to increase the frequency of ACTH-depot dosage.

The fetal cells are genetically heterologous to the mother, but they are tolerated thanks to physical, biochemical, hormonal and immunological tolerance whose potential lack contributes to the spontaneous initiation of child delivery. The increase in the concentration of aminopeptidases in mother's blood is stopped only before the delivery [10,45,46]. Before such true tolerance disappears, a caesarean section performed on request a week or more before the delivery term often results in transfer of pregnancy cells (fetal or afterbirth) outside the reproductive organ (not only to the postoperative skin wound). Subsequent divisions of the cells lead to development of clones with their own vascularization. Prolongation of human life achieved by medicine has resulted by a longer period of old age which is favourable for self-organization of dissipative neoplastic cells. Therefore, as early as in the period of pregnancy reproductive cells should be protected by taking care of gonads, due to their prime importance in the intergenerational passage of life. So far, man has not interfered so often in reproduction on a cell level. Disturbance of systemic psychoimmuno-neuroendocrinological autoregulation causes development of dissipathogenic state of cells. Germ cells, as any other cells of embryo, foetus, neonate and parents are subject to psychoneurocybernetic laws with the second law of thermodynamics being dominant and extended with dissipative structures [13,21-25]. A single zygote defines the unique identity of each person, whose life is determined by free will and neoplasm. Pathological states of cells may regress following neurohormonal normalization and/or immunopotentialisation of their environment, which improves the results of oncological treatment, especially in early stages of the disease [1,2,11,16]. For example, potential and necessary conditions for development of cervical cancer fall within a wide range of factors, from genetic hereditary states to psycho-emotional procreative and sexual reactions. The most common, but at the same time the easiest to eliminate factors - are the constantly increasing cases of abnormal course of pregnancy and birth due to iatrogenic and medial causes, as well as long-term and inadequate use of contraceptive pills [18-21]. Fortunately neoplastic diseases are not infectious, like for example flu, which may develop in spite of previous vaccinations against several types of influenza virus. It is possible to experimentally integrate viruses into genome of animal cell, but the nucleotide sequences that are later isolated are not infectious. In contrast to neoplastic diseases, in infectious diseases it is possible to isolate a cause of the disease from the affected organism, e.g. a virus or bacteria and use it to infect other people. On the other hand, numerous attempts to cause neoplasm in healthy subjects by implanting neoplastic cells in their organisms have not been successful. Therefore, informing a woman about vaccination against cervical cancer, which is actually vaccination against only a few types of human virus, is unnecessary disinformation. Common definition of vaccines as e.g. preventing influenza, or any other infectious disease, may be justified only by the fact that this type of disease cannot appear without at least one type of influenza virus, which is sufficient to cause influenza. Unfortunately, it undergoes constant mutations. Excluding infection, there are many other and much more common factors, e.g. in relation to cervical cancer even 120 [14,15,30].

Do góry

Causal obstetrical prevention of cancer

The introduction of nuclear magnetic resonance (NMR) imaging to the medicine made it possible to verify the thermodynamic theory of neogenesis by recognizing and differentiating between cancerous and precancerous cells, based on cervical and vulval cancers [22,32,33,38]. Thus, completely new opportunities appeared for primary oncological prophylaxis by influencing the environment, and not only cell systems at risk of ending their metabolism in the present form of life among other due to the growing number of operative deliveries and inadequate use of steroid preparations. Recently, an increase of risk for this disease was showed in connection with the use of contraceptive tablets [3,42,43] and, obviously, the risk additionally grows when associated with the infection with human papillomavirus [39]. One cannot omit the fact that it is the very virus that – as its name indicates – infects humans who, when healthy, have been effectively eliminating it for centuries. Only decreased efficiency of biochemical, neurohormonal and/or immunological mechanisms leads to infectious states which, irrespective of their bacterial, viral or parasitic etiology, are only the necessary, but not the sufficient causes of neogenesis. It is not the virus, but only the infection caused by the virus that becomes an oncogenic factor, as the germ itself is a sufficient cause of formation of papilla, which indicates the infectious disease.

The most effective prophylaxis of neoplasms is adequate upbringing and educating every human being to live and work in line with the auto-teleological principles of the concordance between actions and recognized ethical values. Teleology involves aiming at goals in the very cause of each event. The cause of neoplastic diseases (cancer) is a natural and common phenomenon of self-organization of living cells endangered with death into more efficient dissipative spatio-temporal structures, at the expense of their environment. In relation to humans it means that carcinogenesis cannot be eliminated, but it is possible to effectively prevent development of neoplastic diseases, which are more often curable thanks to primary and secondary prevention [20,30,37,40,41,44].

Iatrogenic and social factors predisposing to cervical cancer are well documented and cannot be replaced by any, especially prematurely advertised, medicine. What is particularly evident is the lack of sufficient primary prophylaxis of all diseases in women, which results from following main of obstetrical causes: 1. the increase in the number of operative deliveries and prematurity due to lack of correct understanding of the relative duration of pregnancy, 2. failure to conduct the measuring of the blood levels of oxytocinases (CAP1 and CAP2) as the most stable enzymes regulating the neuroimmunological state of pregnancy, 3. use of dexamethasone and betametasone instead of adrenocorticotropin for preventing miscarriages and prematurity of neonates, and 4. discounting the incidence of the hypothalamic neurohormonal insufficency syndromes as the large causes of the pathological course of pregnancies.

Do góry

References

1. Bałajewicz M, Dembowska J, Klimek R (1989). Test of immunopotentialization in colposcopy - a clinical evaluation. Eur J of Obstet and Gynecol and Reprod Biology. 33: 253 257.
2. Buchner P, Klimek R, Wysokiński A (1988). The results of immunotherapy of cervical lesions in infertile women. International Congress In Vitro Fertilization Jerusalem. Abs p.418.
3. Cogliano V, Grosse I, Baan R. Straif K, Secretan B (2005). Carcinogenicity of combined oestrogen-progestern contraceptives and menopausal treatment. Lancet Oncol. 6: 552-553.
4. Cosmi EV, Klimek R, Di Renzo GC, Kulakov V, Kurjak A, Maeda K et al (1997). Prognosis of birth term: recomendations on current practice and overview of new developments. Archives of Perinatal Medicine. 3(2): 31-50.
5. Fedor-Freybergh PG (1992). Prenatal and Perinatal Psycho-Medicine in changing word. In: Klimek R, editor, Psycho-Medicine Cracow. p. 50-55.
6. Fedor-Freybergh PG (1993). Pathophysiology of Immune-Neuroendocrine Communication Circuit. Editor, together with Gupta D, Wollman HA. Mattes Verlag Heidelberg.
7. Hodorowicz S, Jasiczek D, Klimek R, Tadeusiewicz R (2011). Rak i niepłodność. Prawda i mity medycyny. [(Cancer and infertility. Truth and myth of medicine.) (In Polish)] Trio Kraków-Warszawa.
8. Jasiczek D, Klimek R (2011). Życie i medycyna. [(Life and medicine) (In Polish)] Hermes Management S.A.
9. Klimek M (2005). Comparative analysis of ACTH and oxytocinase plasma concentration during pregnancy. Neuroendocrinology Letters. 26(4):337-341.
10. Klimek M (2006). The effectiveness of adrenocorticotropin repeated doses in high risk pregnancies. Fetal Diagn Ther. 21(6):528-531.
11. Klimek M, Klimek R (1990). Cervical intraepithelial neoplasia after high-risk pregnancy. Gin Pol. 61: 575-577.
12. Klimek M, Klimek R, Mazanek-Mościcka M (1999). Biological diagnosis and prognosis in practical obstetrics. Polish J Gynaec Invest. 2 (2): 57-66.
13. Klimek M, Klimek R, Mazanek-Mościcka M (2002). Preterm birth as an indicator of cancer risk for the mother. It J Gynacol Obstet. 3: 73-77.
14. Klimek M, Klimek R, Skotniczny K at al. (2001). Auxilogical relations between prenatal ultrasound and oxitocinase measurements high-risk pregnancies. J Prenat Neonat med. 6:350-355.
15. Klimek M, Wicherek L, Popiela TJ et al. (2005). Changes of maternal ACTH and oxytocinase plasma concentrations during the first trimester of spontaneous abortion. Neuroendocrinology Letters. 26(4):342-346.
16. Klimek R (1980). Neuroendocrinologic aspects of the dissipative structures of tumors. Mat Med Polona. 1-2: 91-96
17. Klimek R (1986). Immunotherapy of cervical intraepithelial neoplasia. In: Bompiani A, Carenza L, Salvadori B, Pachi A editors. LXIV Congresso Nazionale della Societa Italiana di Ginecologia e Ostetrica. vol. I. 275-278.
18. Klimek R (1990). Cervical cancer as a natural phenomenon. Eur J Obstet Gynecol Reprod Biol. 36: 221 238.
19. Klimek R (1990). Conquering cancer ourselves. New trends in gynecology and obstetrics. J.Libbey CIC s.r.l., Roma Vol. VI No 2: 53-117.
20. Klimek R (1990). Casual prevention of cancer as a natural biological phenomenon. Medicine Biologie Environment. 18: 8-10.
21. Klimek R (1994). Monitoring of pregnancy and prediction of birth date. The Parthenon Publishing Group, New York, London.
22. Klimek R (2001). Biology of Cancer: Thermodynamic Answers to Some Questions. Neuroendocrinology Letters. 22: 413-416.
23. Klimek R (2001). The use in obstetrics of quantum theory as well as modern technology to decrease the morbidity and mortality of newborns and mothers during iatrogenic induced delivery. Neuroendocrinology Letters. 22: 5-8.
24. Klimek R (2007). Cell as biological form of life. Ginekol i Położn. 3(5): 9-17.
25. Klimek R (2010). Cancer: health hazard resulting from attempted life protection. Curr Gynecol Oncol. 8(3) 149-159.
26. Klimek R, Bręborowicz GH, Chazan B, Czajkowski K, Dębski R, Dubcak J, Fedor-Freybergh P et al (2001). Declaration of the Childbirth in XXI century. Archives of Perinatal Medicine. 7(3): 8-14.
27. Klimek R, Dembowska J, Bałajewicz M, Plechanow J (1989). Effect of immunopotentialization on rate of vaginal smear normalization according to appearance of cervical intraepithelial neoplasia. Int J Gynecol Obstet. 28: 41-44.
28. Klimek R, Fedor-Freybergh PG, Walas-Skolicka E (1996). A Time to Be Born. DREAM Cracow.
29. Klimek R, Jasiczek D, Gralek P, Fedor Freybergh P (2011). Cancer – final cellular form of life. Int J Prenat Psychol Medicine. 23, 1-2: 7-17
30. Klimek R, Klimek M, Jasiczek D (2011) Immunotherapy of cervical cancer as a biological dissipative structure. Neuroendocrinology Letters. 32(4): 380-388.
31. Klimek R, Klimek M, Rzepecka-Węglarz B (2000). A new score for postnatal clinical assessment of fetal maturity in newborn infants. Int J Obstet Gynecol. 71:101-105.
32. Klimek R, Lauterbur PC, Mendonca-Dias MH (1981). A discussion of nuclear magnetic resonance (NMR) relaxation time of tumors in terms of their interpretation as self-organizing dissipative structures and of their study by NMR in vivo by NMR zeugmstographic imaging. Gin Pol. 52: 493-498
33. Klimek R, Lauterbur PC, Mann WJ, Mendonca-Dias MH, Kaplan C (1982). Nuclear resonance technique in human surgery. Przegl Lek. 39:335-338.
34. Klimek R, Paradysz A (1971). L’insuffisance hypothalamique de la grossesse: une indication du traitment par L’ACTH syntetique. Rev Fran Endocrin Clin 3:243-249.
35. Klimek R. Walas-Skolicka E (1977). Le syndrome hypothalamique post-gravidique comme agent de risque de developpement de cancer du col uterin. Arch Anat Cytol Path. 25(5): 305-309
36. Liggins GC, Howie RN (1972). A controlled trial of antepartum treatment for prevention of the respiratory distress syndrome in premature infants. Pediatrics, 192:515-519.
37. Lokkegaard E, Jovanovic Z, Heitmann BL, Keiding N, Ottesen B, Pedersen AT (2006) The association between early menopause and risk of ischaemic heart disease: influence of hormone therapy. Maturitas. 53(2): 226-233.
38. Mann WJ, Mendonca-Dias MH, Lauterbur PC, Klimek R (1984). Preliminary in vitro studies of nuclear magnetic resonance relaxation time and three-dimensional nuclear magnetic resonance imaging in gynecological oncology. Am J Obst Gynec. 148:91-96.
39. Moreno V, Bosh FX, Munos N et al (2002). Effect of oral contraceptives on risk of cervical cancer in women with human papilloma virus infection: the IARC multicentric case–control study. The Lancet. 359: 1085-1092.
40. Parker WH, Broder MS, Chang E at al (2009) Ovarian conservation at the time of hysterectomy and long-term health outcomes in the Nurses’ Health Study. Obstet Gynecol. 113(5): 1027-1037.
41. Schenker JG (1992). Stress and human reproduction. In Klimek R (ed): Pre- Peri-Natal Psycho-Medicine. DReAM Cracow, p. 77-82.
42. Smith JS, Green J, Berrington de Gonzalez A et al (2003). Cervical cancer and use of hormonal contraceptives: a systemic review. Lancet. 361, 1159-1167
43. Vessey M, Painter R (2006). Oral contraceptive use and cancer. Findings in a large cohort study, 1968-2004. Br J Cancer. 95: 385-389.
44. Whiteman MK, Hillis SD, Jamieson DJ et al (2008) Inpatient hysterectomy surveillance in the United States, 2000-2004. Am J Obstet Gynecol. 198(1): 34.e1-34.e7.
45. Wicherek L, Klimek M, Dutsch-Wicherek M (2005). The level of maternal immune tolerance and fetal maturity. Neuroendocrinology Letters. 26(5):561-566.
46. Wicherek L, Dutsch-Wicherek M, Mak P, Klimek M (2005). The role of RCAS1 and oxytocinase in immune tolerance during pregnancy. Fetal Dign Ther, 20(5):420-425.

Do góry