Pelvic pain, free fluid in pelvis, and human chorionic gonadotropin serum elevation: recurrence of malignant ovarian germ-cell tumor or early pregnancy?

Conservative treatment of metastatic germ-cell tumor of the ovary does not exclude the possibility of pregnancy in the future. Serum beta-human chorionic gonadotropin (beta-hCG) serves as pregnancy test, and has also been proven to be a useful marker for ovarian germ-cell tumors. This paper is a case report of a 19-year-old patient who was admitted to a district hospital in emergency due to pelvic pain, amenorrhoea, and free fluid in the pelvis. Laboratory tests demonstrated slight increase in beta-hCG serum concentration and transvaginal ultrasound (TVUS) showed no evidence of gestational sac in the uterus. At the age of 14, the patient was diagnosed with malignant germ-cell tumor of the left ovary in FIGO Stage IV and was treated with four courses of chemotherapy according to TGM-95 protocol with etoposide, ifosfamide, and cisplatin, followed by conservative surgery and adjuvant two courses of cytostatics. The initial diagnosis was recurrence of ovarian malignancy and the patient was referred to an oncology center. Wait-and-see approach and repeated ultrasound examination confirmed a normal intrauterine pregnancy which concluded with the delivery of a healthy newborn through cesarean section.

Phenotype of dendritic cells generated from peripheral blood monocytes of patients with ovarian cancer.

OBJECTIVES: The aim of our study was to generate dendritic cells (DCs) from peripheral blood monocytes (PBMC) of patients suffering from ovarian cancer. MATERIALS AND METHODS: Immature DCs were generated from PBMC cultured in RPMI 1640 medium with 2% human serum albumin (HSA), supplemented with recombinant human (rh) granulocyte macrophage colony stimulating factor (GM-CSF) and rh interleukin (IL)-4. After 5 days of culture, DC maturation was induced by the addition of an ovarian cancer cell line (CAOV3) lysate and after 6 days of rh tumor necrosis factor (TNF)-α for a further 2 days. The phenotype of the generated cells was assessed by flow cytometry for the expressions of human leukocyte antigen (HLA)-DR, costimulatory molecules (e.g., CD86, CD80), CD83, CD1a, and CD14. PBMC cultured in 2% HSA without rhIL-4, rhGM-CSF, rh-TNF-α, or tumor cell lysate formed the control group. RESULTS: The 2.41% (interquartile range, 1.51%-3.52%) of CD45+/CD14+ cells in cultures with rhIL-4, rhGM-CSF, rhTNF-α and tumor cell lysate was significantly lower than in the control group (31.10%; interquartile range, 11.11%-64.06%). Cultures with rhIL-4, rhGM-CSF, rhTNF-α, and tumor cell lysate showed a higher percentage (19.96%; interquartile range, 9.30%-24.42%) of fully mature CD83+/CD1a-/HLA-DR+ DCs compared with control culture (6.02%; interquartile range, 3.01%-7.37%). There was no significant difference in the expression of the immature DC marker (CD1a) between the cultures. The expression of co-stimulatory markers (CD80, CD86, HLA-DR) was greater (24.29%; interquartile range, 18.68%-33.95%) on DCs from cultures with rhIL-4, rhGM-CSF, TNF-α, and tumor cell lysate versus controls (4.93%; interquartile range, 2.67%-9.09%). CONCLUSION: Our data demonstrated that immature and mature DCs can be generated from adherent human PBMC from ovarian cancer patients cultured with rhIL-4, rhGM-CSF, rhTNF-α, and tumor cell lysates.

Is hypothermia a benefit? Von Willebrand factor in pediatric cardiopulmonary bypass.

AIM: The use of cardiopulmonary bypass (CPB) is associated with the risk of development of postpump syndrome. Thrombocyte activation leads to microembolism, endothelial damage and necrosis with release of various substances, such as the von Willebrand factor (vWf). High levels of vWf increase the risk of postoperative complications and mortality. Our objective was to find a correlation between CPB and plasma levels of vWf in pediatric patients operated on for congenital heart defects. METHODS: Twenty patients with congenital heart defects (ventricular septal defect, atrial septal defect/partial anomalous pulmonary vein drainage, Bland White Garland syndrome) were operated on with the use of CPB. The arterial blood was sampled after induction of anesthesia, 5 minutes after commencing CPB, 1 hour and 3 hours after surgery. The plasma levels of vWf were measured and compared to selected clinical findings. RESULTS: There was no early mortality. There were no significant differences in CPB and aortic cross clamp times when compared in patients with various defects. vWf plasma levels were significantly elevated in all patients 1 hour and 3 hours after surgery. We found no correlation between vWf levels and type of defect, CPB duration, aortic cross clamp as well as reperfusion time. However, we were able to demonstrate that the observed elevation of vWf levels was almost 4-fold higher in patients cooled down to lower temperatures (15 patients; mean rectal value 27.64+/-0.7 degrees C) than in 5 patients (mean rectal temperature 30.74+/-1.56 degrees C) where only slight elevation was found. There were no differences in the postoperative course of these patients. All patients were discharged from hospital 10+/-3 days after operation (mean value 9 days). CONCLUSIONS: vWf plasma levels are significantly elevated after pediatric hypothermic CPB. It seems that the augmentation of vWf values could be independently associated with rate of hypothermia.

Multiple effects of theobromine on fetus development and postnatal status of the immune system.

Caffeine and its active derivative, theobromine, are probably the most frequently ingested pharmacologically active substances. Considering their uninhibited transport via the placental barrier as well as immature enzymatic activities and metabolic pathways in embryos and infants resulting in the longer half-life of methyloxanthines and their accumulation, unrestrained uptake of these substances might result in noticeably more pronounced biological effects during pregnancy and the postnatal period. Our previous studies have shown that methyloxanthines are significant inhibitors of angiogenic growth factors production and angiogenesis itself. We have hypothesized that increased uptake of these substances might affect embryonal angiogenesis and, later in the postnatal period, maturation and functional activity of the offspring's immune system. The study was performed on 2-month-old Balb/c mice fed theobromine 2 or 6 mg/day during pregnancy and lactation. On day 18 of pregnancy the number and weight of embryos were assessed as was their tissue angiogenic activity, using the cutaneous angiogenesis assay. In the group of 4-week-old sucklings, body and spleen were weighed together with the trunk, and tail and limb length were measured. Six weeks after birth the splenocytes' mitogen-induced activity and their ability to induce graft-versus-host reaction as well as the humoral response to SRBC antigen were evaluated. Content of theobromine in the embryos' tissue was estimated by high liquid performance chromatography (HPLC). Theobromine feeding resulted in significant inhibition of embryo growth as assessed by their weight and decreased angiogenic activity of their tissue. The theobromine content in embryo tissue from treated groups was higher than in the controls, and the difference was close to significant. In the postnatal period the discrepancies in the treated 4-week-old group's development were also observed in the significantly shorter limbs in comparison to the controls. Moreover in the treated group of 6-week-old sucklings, considerable variations in the immune system's functional activity were registered as far as cellular and immune response were concerned. Respectively, the splenocytes' mitogen-induced proliferative activity was significantly suppressed while the graft-versus-host reaction was up-regulated, and the serum antibodies titer was elevated in correspondence to the observed spleen enlargement. We concluded that a theobromine-enriched diet affects progeny development in both prenatal and postnatal periods. Consequently, particular attention should be paid to the reduction of theobromine consumption, and most probably that of other methyloxanthines, during pregnancy and lactation.

Immunomodulatory effect of shikonin derivatives isolated from Lithospermum canescens on cellular and humoral immunity in Balb/c mice.

The immunomodulatory activity of acetylshikonin (ACS) and isobutyrylshikonin (IBS) was studied in female and male inbred Balb/c mice, and in F1 hybrids (Balb/c x C3H). ACS and IBS were isolated from Lithospermum canescens Lehm. (Boraginaceae) roots. Splenocytes from mice fed 40 microg of ACS had higher proliferative potential in cultures with PHA than corresponding controls and also higher migratory in vitro activity than splenocytes obtained from control animals. ACS at a 40 microg daily dose stimulated G-v-H reaction but inhibited it at a 200 microg dose. IBS at a 40 microg dose significantly increased humoral response.

The influence of Eleuterococcus senticosus on cellular and humoral immunological response of mice.

The influence of Eleuterococcus senticosus on cellular and humoral immune response was evaluated. The experiments were performed on animal models (Balb/c mice and F1 crossbreeds Balb/cxC3H). It was shown that Eleuterococcus has immunomodulatory properties. This substance enhanced the cellular response of the mouse immunological system (chemokinetic activity of mice spleen cells, GvH reaction). A stimulatory effect of Eleuterococcus on the humoral response (antibody production) was also observed. Eleuterococcus did not augment the angiogenic activity of human renal carcinoma cells.

Inhibitory effect of Greenland shark liver oil combined with squalen and arctic birch ashes on angiogenesis and L-1 sarcoma growth in Balb/c mice.

Sharks have been claimed to be resistant to cancer and oil from their livers have been used in Scandinavian folk medicine as anti-tumor drug. Shark liver oil contains 40% or more of squalene. Fish liver oil is also rich in squalene and polyunsaturated n-3 fatty acids. The aim of this work was to determine the anti-angiogenic and anti-tumor effects of these substances, together with another Scandinavian traditional remedy--arctic birch ashes--in Balb/c mice after transplantation of syngeneic L-1 sarcoma. All substances tested, alone or in combinations, significantly diminished cutaneous angiogenesis induced by tumor cells, and tumor growth.

Chocolate feeding of pregnant mice influences length of limbs of their progeny.

UNLABELLED: We previously reported the inhibitory effect of various methyloxantines and phenolic compounds on tumor-induced angiogenesis and the production of angiogenic growth factors. The aim of the present work was to evaluate the effect of chocolate (CH), food containing substantial amounts of methyloxantine theobromine and polyphenols (mainly catechins), given to mice during pregnancy and the lactation period, on weight of organs, length of limbs, and bone vascular endothelial growth factor (VEGF) concentration (tested by ELISA), in 4-week old offspring. The study was performed on 2-month old Balb/c mice fed during pregnancy and lactation 400 mg of CH daily. Content of polyphenols (catechines) and theobromine in the chocolate was estimated by high liquid perforance chromatography (HPLC). Concentration of VEGF was tested by ELISA. Feeding pregnant mice chocolate produced the following effects: decrease of relative length of limbs and thigh bones in 4-week old progeny and decrease in VEGF content of offspring femoral bones. CONCLUSION: attention should be paid to possible unwanted effects of catechine- and methyloxantine-rich food and beverages during pregnancy and lactation. 200 mg of chocolate per mouse corresponds to 100 g per person.

[The effect of small cell lung cancer extension on secretion of interleukin-2 (IL-2) and interferon gamma (IFM gamma) in whole blood culture stimulated with mitogens]. / Wplyw rozleglosci drobnokomórkowego raka pluca na wydzielanie interleukiny 2 (IL-2) i interferonu gamma (IFN gamma) w hodowli pelnej krwi stymulowanej mitogenami.

The aim of this study was to assess the role of SCLC extension on II-2 and IFN gamma secretion in whole blood cell cultures stimulated with mitogens. Material consisted of 42 SCLC patients, 19 with extensive and 23 with limited disease. In 22 patients partial or complete regression of tumour occurred after treatment. There was a tendency to lower II-2 and IFN gamma secretion before treatment in patients with extensive disease in comparison to those with limited lesions but this was not statistically significant. The ability to secrete cytokines in 22 patients after partial or complete regression of tumour decreased or increased but median values after treatment were not statistically different from those before treatment.

Interferon gamma and interleukin-2 secretion in whole blood cell cultures from small-cell lung cancer patients.

Secretion of interleukin-2 (IL-2) and interferon-gamma (IFNgamma) in whole blood cell cultures after phytohemagglutinin (PHA) and pokeweed mitogen (PWM) stimulation was evaluated in 42 small-cell lung cancer patients before treatment. Blood cultures from patients with extensive and limited disease have lower IFNgamma secretions after PWM stimulation and lower IL-2 secretions after PWM and PHA stimulation, but this was not statistically significant. IFNgamma but not IL-2 secretion was significantly higher after PWM stimulation in cultures from patients with better clinical performance status (0 + 1, WHO scale). Blood cultures from patients with tumor regression after treatment had a higher secretion of IFNgamma after PWM stimulation. In contrast, blood cultures from patients with a poor prognosis had significantly lower IL-2 and IFNgamma secretions after stimulation with PWM, and a lower IL-2 secretion after stimulation with PHA.

Assessment of the VEGF, bFGF, aFGF and IL8 angiogenic activity in urinary bladder carcinoma, using the mice cutaneous angiogenesis test.

Development of new blood vessels in solid tumors depends on changes in equilibrium between angiogenic stimulators and inhibitors. Overexpression of angiogenic growth factors has been shown in bladder carcinoma. The 'mice cutaneous angiogenesis test' is a good method for assessment of the total angiogenic potential of bladder cancer tissue. The analysis of the levels of proangiogenic factors could be useful for the choice of properly directed angiogenesis inhibitors. The aim of our study was to investigate the influence of blocking some angiogenic factors on the angiogenic activity of bladder cancer tissue. Tumor tissue obtained from 12 patients with invasive bladder carcinoma was used. Cancer tissue homogenates were incubated in the presence of specific antibodies against VEGF, bFGF, Il-8 and aFGF. Cytokine levels were determined using the ELISA test. Cutaneous angiogenesis assay in Balb/c mice was performed to detect the angiogenic activity of the tumor tissue. VEGF, bFGF and Il-8 were present in all examined cancer tissues (aFGF level was not estimated). Cytokine concentration and angiogenic activity of bladder cancer tissue showed individual variation. There was no correlation between the cytokines content in tumor tissue and the ability of this tissue to induce angiogenesis. Absorption caused significant reduction in cytokines level. The reduction of angiogenic activity was observed in the cancer tissue of 1 patient after VEGF absorption, in 3 patients' tissue homogenates after incubation with anti-aFGF and in 2 patients' homogenates after bFGF absorption. There was no reduction of angiogenic activity after Il-8 absorption.

Angiotensin-converting enzyme activity and angiomodulatory effects of sera in patients with diabetic retinopathy.

Aberrant neovascularization plays a crucial role in ocular complications in diabetic patients. Sera from these patients contain high levels of angiostimulatory factors, the most important of which is vascular endothelial growth factor (VEGF). Many authors have described elevation of angiotensin-converting enzyme (ACE) activity in the sera of diabetic patients. It is important to determine the possible relationship between these two phenomena. We studied ACE serum activity and VEGF concentrations in patients with type 1 and type 2 diabetes and retinopathy We also investigated the effect of their sera on cutaneous angiogenesis induced in mice by grafting healthy human mononuclear blood leukocytes. We found a negative correlation between the angiostimulatory effect and ACE level in the sera of patients with type 1 diabetes and no correlation between these two parameters in patients with type 2 diabetes. VEGF concentrations were lower and ACE activity was significantly higher in the sera of patients with type 1 diabetes than in the sera of those with type 2 diabetes.

Inhibitory effect of shark liver oil on cutaneous angiogenesis induced in Balb/c mice by syngeneic sarcoma L-1, human urinary bladder and human kidney tumour cells.

The effect of shark liver oil on cutaneous angiogenesis induced in mice by intradermal grafting of tumour cells was evaluated. It was shown that this substance (Ecomer) suppressed neovascular response in mice grafted with sarcoma L-1 syngeneic cells, human kidney cancer and human urinary bladder cancer cells. In addition, strong stimulatory effect of this drug on mice blood granulocyte number and their metabolic activity was observed.

[The evaluation of atrial natriuretic peptide and endothelin in serum of the patients with non-atopic bronchial asthma during exacerbation]. / Ocena stezen przedsionkowego peptydu natriuretycznego i endoteliny u chorych na astme oskrzelowa nieatopowa podczas zaostrzenia choroby.

The aim of the study was to evaluate concentrations of atrial natriuretic peptide (ANP) and endothelin in blood serum of the patients with nonatopic bronchial asthma in the exacerbation phase and during non-symptomatic period. The study included 20 patients with nonatopic bronchial asthma (10 women and 10 men, mean age 34.2) treated in the Allergological Outpatient Clinic in Zabrze (Poland). A control group consisted of 5 healthy volunteers without atopy. The study consisted of evaluation of the ANP and endothelin in blood serum by radioimmunoassay and by functional respiratory tests. It was shown that ANP concentrations during bronchial asthma exacerbation were two times lower than in the same group examined in the remission phase (7.8-13.7 pmol/ml, p < 0.05). At the time of bronchospastic symptoms occurrence, the concentrations of endothelin were statistically significant and higher than in the non-symptomatic group (11.6-6.9 pmol/ml, p < 0.05). In the examined group the reverse proportion relation between concentrations of the studied peptides in blood serum was observed r = -0.56, p < 0.05 according to Spearman test.

[Secretion of interleukin-2 (IL-2) and interferon (IFN gamma)in whole blood cell culture stimulated with mitogens in patients with lung neoplasms]. / Wydzielanie interleukiny-2 (IL-2) i interferonu (IFN gamma) w hodowli z pelnej krwi stymulowanej mitogenami u chorych na raka pluca.

UNLABELLED: The aim of this study was to compare the ability of blood lymphocytes from lung cancer patients to secrete interleukin-2 (IL-2) and interferon gamma (IFNg) upon stimulation with mitogens with that of healthy donors. 42 patients with small cell lung cancer (SCLC), 30 patients with non small cell lung cancer (NSCLC) and 30 healthy donors were studied. The test was done in lung cancer patients before treatment. IL-2 and IFNg levels were measured with Elisa ready kits (Genzyme) in the supernatants of whole blood culture after stimulation with Pokeweed (PWM) and Phytohemagglutinin (PHA) mitogens. The results of the cytokine levels after stimulation were not normally distributed and thus were transformed to logarthms for statistical evaluation. The t-test for transformed results were used to asses the difference between groups. The median level of IFNg in the supernatant of whole blood cultures was significantly lower in lung cancer patients than in healthy blood donors both after PWM as well as after PHA stimulation. When patients with NSCLC and SCLC were regarded separately the lower level of IFNg in comparison with healthy donors was found in the supernatant of the blood cultures only after stimulation with PWM. The median level of IL-2 in the supernatant of whole blood culture in lung cancer patients was lower than in healthy blood donors only after PWM stimulation. The same was true for SCLC patients. In NSCLC IL-2 levels were significantly lower after stimulation with PWM as well after PHA stimulation. IN CONCLUSION: secretion of IL-2 and IFNg in whole blood culture after mitogen stimulation in lung cancer patients is significantly lower than in healthy donors. No significant differences between SCLC and NSCLC were found.

The effect of salbutamol treatment on the cellular immunity of the offspring of pregnant mice: spleen cell activity.

Preterm delivery is one of the greatest problems in obstetric care. One of the most commonly used treatments for high risk cases is salbutamol, a beta-2-adrenoceptor agonist. The aim of the present study was to determine if such treatment causes any changes in the neonatal immune system which should therefore be a concern in the care of the newborn. The experiments were performed on 4 to 5 or 6 to 7-week old female and male offspring of salbutamol-treated C3H/W inbred mice. In the first part of the study, the number of spleen cells, phenotypes and activity (phytohemagglutinin-induced proliferation, ability to induce local graft versus host reaction) were determined. We observed lowering of cell number and lowered proportions of cluster of differentiation (CD)3, CD4 and CD8 positive lymphocytes in spleens of progeny of salbutamol-treated mice. However, CD4+ to CD8+ ration was higher in the progeny of salbutamol-treated mothers than in the corresponding controls. In addition, reactivity to phytohemagglutinin and ability to induce local graft vs. host reaction were higher (popliteal lymph node test) or undisturbed (lymphocyte-induced angiogenesis test) in this group of mice.

Assessing and optimizing the performance of a phase-shifting interferometer capable of measuring the complex index of refraction and the surface profile of a test surface.

A novel interferometer based upon a conventional phase-shifting design is further investigated. This interferometer is capable of measuring both the real and imaginary parts of the complex index of refraction and the surface profile of a test surface. Maximum-likelihood estimation theory is shown to be an effective means of extracting the three parameters of interest from the measured data. Cramér-Rao lower bounds are introduced as a means of quantitatively assessing the performance of the system. Furthermore, it is shown that as the design parameters are optimized, the results approach the theoretical performance limit. We conclude by developing the underlying theory behind the relationship of the complex-index-of-refraction estimates to the surface-profile estimate.

Phase-shifting interferometer/ellipsometer capable of measuring the complex index of refraction and the surface profile of a test surface.

A novel interferometer based on a conventional phase-shifting design is presented. This interferometer is capable of measuring both the real and the imaginary parts of the complex index of refraction and the surface profile of a test surface, n, k, and h, respectively. Maximum-likelihood-estimation theory is shown to be a viable means of extracting the three parameters of interest from the measured data. A Monte Carlo simulation showed limited success in estimating the complex index parameters. The results exhibited bias or deviation from the true values for the system configuration examined. The estimate on the surface profile showed excellent agreement with the true value, although the error in the estimate was an order of magnitude worse than in the case in which only the surface profile is to be estimated.

Phase-Shifting Interferometry and Maximum-Likelihood Estimation Theory. II. A Generalized Solution.

A novel means of quantitatively assessing the performance of a phase-shifting interferometer is further investigated. We show how maximum-likelihood estimation theory can be used to estimate the surface profile from the general case of M noisy, phase-shifted measurements. Monte Carlo experiments show that the maximum-likelihood estimator is unbiased and efficient, achieving the theoretical Cramér-Rao lower bound on the variance of the error. We then use Monte Carlo experiments to compare the performance of the maximum-likelihood estimator with that of two conventional algorithms.

[Secondary osteoporosis in patients with steroid-dependent asthma]. / Wtórna osteoporoza u chorych ze steroidozalezna astma oskrzelowa.

The aim of the trial was estimation of frequency and degree of osteoporosis in steroid-dependent asthma patients (48 persons: 18 men and 30 women). Control group created 36 healthy persons. Following measurements were done: quantitative computed tomography, radiological estimation of thoracic and lumbal spinal column and hands, in serum total alkaline phosphatase, calcium, phosphate, in urine excretion of calcium, phosphate and creatinine. Quantitative computer tomography revealed secondary osteoporosis in 40.5% asthma patients. These results were correlated with estimation of roentgenograms of thoracic and lumbal spinal column and metacarpal measurements and less well with total alkaline phosphatase. Time of duration of steroid therapy and time of asthma had influence on degree of osteoporosis. Moderate development of osteoporosis is probably the result of low dose of steroids.