Coronary artery calcium distribution and interscan measurement variability in end-stage renal and coronary heart disease patients.

BACKGROUND: Coronary heart disease patients and end-stage renal disease patients have been documented to have an increased amount of coronary artery calcifications (CAC). PURPOSE: To evaluate the distribution of CAC and its influence on interscan variability of measurement in end-stage renal disease and coronary heart disease patients, proven to have calcifications. MATERIAL AND METHODS: 69 patients having CAC, including 34 with coronary heart disease and 35 with end-stage renal disease, were scanned twice with multidetector-row computed tomography (MDCT). Amount of CAC was determined as the number of calcified lesions (CN), total calcium score (CS), calcium volume (CV), and calcium mass (CM). Distribution of CAC was evaluated on a per-patient basis as the median CS and CM of a single lesion. Density of the calcifications was calculated as the patient's CM divided by CV. RESULTS: The overall median CS was 457.2, and the median CM was 75.6 mg. There were no significant differences in the number of calcified lesions, CS, or CM between the two groups. Both CS and CM of a single lesion, as well as the mean calcium density were lower in renal disease patients (P<0.05) than in coronary heart disease subjects. The relative interscan variability of coronary calcium measurement was higher in the renal disease group (P<0.05). There was a negative correlation between the calcium concentration and the relative interscan variability. CONCLUSION: The results indicate that the coronary calcium distribution influences the measurement interscan reproducibility, and the distribution may differ between end-stage renal disease patients and coronary heart disease patients, reflecting the dissimilar nature of coronary calcifications in those groups.

Reproducibility of dynamic computed tomography brain perfusion measurements in patients with significant carotid artery stenosis.

BACKGROUND: Perfusion computed tomography (PCT) determination is a minimally invasive and widely available technique for brain blood flow assessment, but its application may be restricted by large variation of results. PURPOSE: To determine the intraobserver, interobserver, and interexamination variability of brain PCT absolute measurements in patients with significant carotid artery stenosis (CAS), and to evaluate the effect of the use of relative perfusion values on PCT reproducibility. MATERIAL AND METHODS: PCT imaging was completed in 61 patients before endarterectomy, and in 38 of these within 4 weeks after treatment. Cerebral blood flow (CBF), cerebral blood volume (CBV), time to peak (TTP), and peak enhancement intensity (PEI) were calculated with the maximum slope method. Interexamination variability was evaluated based on perfusion of hemisphere contralateral to the treated CAS, from repeated examinations. Interobserver and intraobserver variability were established for the untreated side, based on pretreatment examination. RESULTS: Interobserver and intraobserver variability were highest for CBF measurement (28.8% and 32.5%, respectively), and interexamination variability was the highest for CBV (24.1%). Intraobserver and interobserver variability were higher for absolute perfusion values compared with their respective ratios for CBF and TTP. The only statistically significant difference between perfusion values measured by two observers was for CBF (mean 78.3 vs. 67.5 ml/100 g/min). The interexamination variability of TTP (12.1%) was significantly lower than the variability of other absolute perfusion measures, and the interexamination variability of ratios was significantly lower than absolute values for all the parameters. CONCLUSION: In longitudinal studies of patients with chronic cerebral ischemia, PCT ratios and either TTP or CBV are more suitable measures than absolute CBF values, because of their considerably lower inter- and intraobserver variability. Differences in CBF between two examinations as high as 30% may be considered as significant in such patients.

Phantom-calibrated versus automatic coronary artery mass quantification with multidetector-row computed tomography: in vitro and in vivo study.

BACKGROUND: Coronary artery calcium scoring is used as a method for cardiovascular risk stratification and monitoring of coronary heart disease. Automatic software-based calcium mass calculation has been proposed to improve the performance of the procedure. PURPOSE: To compare two algorithms of calcium mass measurement, automatic and phantom calibrated, with respect to correlation, measurement error, and accuracy in vitro and in vivo. MATERIAL AND METHODS: A cardiac phantom with calcium cylinder inserts was scanned with sequential non-overlapping collimation 4 x 2.5 mm, at 120 kV and 165 mAs. Fifty adults (37 men; mean age 46.2 years) were examined with the same settings using prospective electrocardiographic triggering to detect and quantify coronary artery calcifications. Calculations were performed with two methods: software-based automatic calcium mass measurement (ACM) and phantom-calibrated calcium mass measurement (CCM). RESULTS: The total phantom calcium masses measured with ACM and CCM were 175.0+/-13.8 mg and 163.0+/-4.4 mg, respectively (P<0.0001), and ACM produced a higher mean error (4.5 vs. 3.2; P<0.05). Results of ACM and CCM were strongly correlated to each other (R=0.73-0.96; P<0.0001). Mean image noise in the patient study was 8.72+/-1.68 HU. Results of patient calcium scoring with ACM and CCM were significantly different (median 70.3 mg and 59.7 mg, respectively; P<0.0001), with a mean systematic error of 17.5% (limit of agreement between 14.6% and 20.4%). The use of ACM resulted in an altered quartile classification for 14% of patients, as compared to CCM; all of these patients were classified into a higher category. CONCLUSION: Our data indicate that multidetector-row computed tomography coronary calcium mass determination based on dedicated phantom calibration shows lower measurement error than an automatic software-based calculation method. The tested automatic software does not yet seem to be a reliable option for calcium mass measurement.

[Usefulness of thoracic imaging and computed tomography in evaluation of neoplastic changes of lungs and mediastinum in children]. / Przydatnosc zdjecia przegladowego klatki piersiowej i tomografii komputerowej w ocenie zmian nowotworowych pluc i sródpiersia u dzieci.

Radiological methods of imaging diagnostics allow to evaluate exactly and to monitor the treatment course of pathological lesions in chest. Basic examinations are: plain chest X-ray and computer tomography. Optimal diagnostic algorithm of neoplastic changes in chest is not always univocally defined. The aim of the study is to compare the results of estimation of the presence and type of neoplastic changes in mediastinum and lungs based on X-ray and computer tomography. The results indicate that initial and control X-ray examination allows to diagnose mediastinal lymphadenopathy coexisting with pulmonary hilus extension. CT is used to diagnose and monitor lung tissue and mediastinal changes.

Adamantylaminopyrimidines and -pyridines are potent inducers of tumor necrosis factor-alpha.

A series of (1-adamantyl)aminopyrimidine and -pyridine derivatives was prepared by adamantyl cation attack on amino heterocycles. The adamantylated compounds, particularly 2-(1-adamantyl)amino-6-methylpyridine, were found to be potent TNF-alpha inducers in murine melanoma cells transduced with gene for human TNF-alpha.

Potentiatied antitumor effectiveness of combined chemo-immunotherapy with interleukin-12 and 5-fluorouracil of L1210 leukemia in vivo.

In this study we investigated the efficacy of a combination of IL-12 and 5-FU, a chemotherapeutic exerting several immunomodulatory effects, in murine L1210 leukemia. Mice inoculated with 1 x 10(5) leukemia cells were treated with a single dose of 5-FU (50 mg/kg) and seven daily doses of IL-12 (100 ng/dose), and were observed for survival. Treatment with IL-12 or 5-FU given alone produced moderate anti-leukemic effects. However, combination of both drugs resulted in a significant prolongation of mouse survival time. Importantly, there were 70% of long-term (>60 days) survivors among mice treated with both agents simultaneously. Moreover, we observed 100% of long-term survivors when mice were treated with a minimally increased dose of IL-12 (170 ng) in combination with 5-FU (50 mg/kg). The antileukemic effects were completely abrogated in scid/scid mice and in mice depleted of peritoneal macrophages and significantly decreased after administration of anti-CD3+, anti-CD4+ or anti-CD8+ monoclonal antibodies. Administration of anti-NK1.1 antibodies did not decrease the antileukemic effects indicating that NK cells are not important effectors of this treatment regimen. Collectively, these results indicate that the combination of IL-12 and 5-FU is inducing strong antileukemic responses that are dependent on the presence and activity of macrophages and T lymphocytes and warrant further studies of combined chemo-immunotherapy with IL-12.

Butyric acid enhances in vivo expression of hTNF-alpha in transduced melanoma cell line.

Butyric acid (NaBut) and its derivatives are well-known agents eliciting tumor cell differentiation and apoptosis. In experimental models, NaBut is also used to enhance the efficacy of viral vectors. With the use of B78 murine melanoma cells transduced with the retroviral vector containing human tumor necrosis factor alpha (hTNF-alpha) gene, we investigated the ability of NaBut to increase the cytokine expression. We observed an increase in hTNF-alpha expression in vitro after incubation with NaBut. We also describe that the NaBut pro-drug tributyrin is able to increase hTNF-alpha expression in transduced B78 cells in a tumor vaccination model in mice. This observation strongly suggests a novel potential role for NaBut and its derivatives in tumor therapy. It could be used not only as a therapeutic directly acting on tumor cells but, in parallel, as a genetic vaccine "enhancer".

Synthesis, structure and tumour necrosis factor-alpha production-enhancing properties of novel adamantylamino heterocyclic derivatives.

The synthesis of several adamantylated aminoheterocycles is reported. The attack of the adamantyl cation formed from 1-adamantanol in refluxing trifluoroacetic acid or induced by microwave irradiation provides adamantylamino-derivatives of respective heterocycles. Adamantylated heterocycles enhance the induction of tumour necrosis factor alpha (TNF-alpha) in genetically modified murine melanoma cells transduced with the gene for human TNF-alpha. Of the studied collection of adamantylated compounds, the most biologically active are 2-adamantylamino-6-methylpyridine and 2-adamantylamino4-methylpyrimidine. The crystal structure of 2-adamantylamino-6-methylpyridine is reported.

[Isolated sphenoiditis treated with endoscopic surgery in a child]. / Izolowane zapalenie zatoki klinowej u dziecka leczone metoda endoskopowa.

Isolated sphenoiditis in childhood is a rare entity which is often very difficult to diagnose with conventional techniques. The authors present a case of sphenoiditis in nine years old boy, where chronic rhinitis and persistent cephalqia where the main symptoms. The diagnosis was made on the base of computed tomography and nasal endoscopy. Because of lack of effect after pharmacological treatment the child was submitted to endoscopic surgery--sphenoethmoidectomy, which resulted it total recovery. The diagnosis, indications to computed tomography of paranasal sinuses in children, options of both conservative and surgical treatment and possible complications of the diseases are discussed.

Potentiation of the anti-tumour effects of Photofrin-based photodynamic therapy by localized treatment with G-CSF.

Photofrin-based photodynamic therapy (PDT) has recently been approved for palliative and curative purposes in cancer patients. It has been demonstrated that neutrophils are indispensable for its anti-tumour effectiveness. We decided to evaluate the extent of the anti-tumour effectiveness of PDT combined with administration of granulocyte colony-stimulating factor (G-CSF) as well as the influence of Photofrin and G-CSF on the myelopoiesis and functional activity of neutrophils in mice. An intensive treatment with G-CSF significantly potentiated anti-tumour effectiveness of Photofrin-based PDT resulting in a reduction of tumour growth and prolongation of the survival time of mice bearing two different tumours: colon-26 and Lewis lung carcinoma. Moreover, 33% of C-26-bearing mice were completely cured of their tumours after combined therapy and developed a specific and long-lasting immunity. The tumours treated with both agents contained more infiltrating neutrophils and apoptotic cells then tumours treated with either G-CSF or PDT only. Importantly, simultaneous administration of Photofrin and G-CSF stimulated bone marrow and spleen myelopoiesis that resulted in an increased number of neutrophils demonstrating functional characteristics of activation. Potentiated anti-tumour effects of Photofrin-based PDT combined with G-CSF observed in two murine tumour models suggest that clinical trials using this tumour therapy protocol would be worth pursuing.

Interleukin 12 and indomethacin exert a synergistic, angiogenesis-dependent antitumor activity in mice.

Nonsteroidal anti-inflammatory drugs have been shown to reduce the incidence and mortality from colorectal cancer. It has recently been demonstrated that these drugs are capable of suppressing the production of pro-angiogenic factors from tumor cells. The mechanisms of antitumor action of interleukin 12 include the enforced secretion of anti-angiogenic factors and stimulation of antitumor immunity. Therefore, we hypothesized that the combination of a model nonsteroidal anti-inflammatory drug--indomethacin and interleukin 12--would result in enhanced angiogenesis-dependent antitumor effects against a colon-26 carcinoma cells transplanted into syngeneic mice. As expected the combined administration of both agents simultaneously resulted in a strengthened antitumor activity that was manifested as a retardation of tumor growth and prolongation of mouse survival. Importantly some mice were completely cured after the combined treatment. As administration of interleukin 12 and indomethacin resulted in enhanced inhibition of angiogenesis it seems possible that prevention of new blood vessel formation is one of the mechanisms responsible for the observed antitumor effects.

Antitumor effects of the combination therapy with TNF-alpha gene-modified tumor cells and interleukin 12 in a melanoma model in mice.

In the present study, TNF-alpha gene-transduced B78 melanoma cells (B78/TNF) were used as a vaccine and combined with interleukin (IL)-12 in the treatment of B78 melanoma-bearing mice. The combined administration of genetically modified melanoma cells and IL-12 induced specific protective antitumor immunity resulting in a decreased rate of the tumor take following a rechallenge with parental B78 cells. When used therapeutically, intratumoral injections of irradiated B78/TNF melanoma cells and IL-12 exerted strong antitumor effects and led to complete regression of established tumors in 50% of mice. Injections of irradiated B78/TNF cells alone did not influence tumor development and IL-12 itself significantly delayed tumor growth but without curative effect. FACS analysis of parental B78 melanoma cells and its B78/TNF genetically modified variant showed that a proportion of cells of both cell lines expressed 87-1 (CD80) costimulatory molecule and that the expression of this molecule was increased during incubation with IFN-gamma. Moreover, IFN-gamma markedly augmented expression of major histocompatibility class (MHC) class I and II molecules on B78/TNF cells that were primarily MHC class I and II negative with no substantial effect on MHC-negative parental B78 melanoma. IFN-gamma also synergized in cytostatic/cytotoxic effects with TNF-alpha against B78 melanoma in vitro. Lymphocyte depletion studies in vivo showed reduction of the antitumor response in mice treated with anti - NK monoclonal antibodies (mAbs) as well as in mice treated with anti-CD4+ anti-CD8 mAbs. The results suggest that, when used therapeutically, IL-12 and a vaccine containing TNF-alpha gene-transduced tumor cells may reciprocally augment their overall antitumor effectiveness by facilitating development of systemic antitumor immunity and by stimulating local effector mechanisms of the tumor destruction.

Potentiatied anti-tumor effectiveness of combined therapy with interleukin-12 and mitoxantrone of L1210 leukemia in vivo.

In previous studies we have shown that combined chemo-immunotherapy of L1210 leukemia with IL-12 and doxorubicin results in striking anti-tumor effects producing 100% of long-term survivors. In this study we investigated the efficacy of a combination of IL-12 and mitoxantrone in murine L1210 leukemia. Mice inoculated with 1x105 leukemia cells were treated with a single dose of mitoxantrone and seven daily doses of IL-12, and were daily observed for survival. Treatment with IL-12 or mitoxantrone given alone produced moderate anti-leukemic effects. However, combination of both drugs resulted in a significant prolongation of mouse survival time. Importantly, there were almost 50% of long-term (>60 days) survivors among the mice treated with both agents. This therapeutic effect was completely abrogated by sub-lethal, whole-body X-irradiation, and significantly reduced after macrophage depletion.

[The significance of the Doppler techniques -- "color Doppler" and "power Doppler" -- in the diagnostic ultrasonography of the eyeball]. / Miejsce metod dopplerowskich color Doppler i power Doppler w ultrasonograficznej diagnostyce galki ocznej.

The eyeball is perfectly suited for ultrasound examination due to its location and structure. The ultrasound examination including the "color Doppler" and "power Doppler" option was performed in 59 patients. Ophthalmologists requested ultrasound examination in those patients mainly in order to confirm and differentiate retinal ablation or because of opacity of vitreous body of the eye. The ultrasound examination was performed with a Logiq 500 f-y GE unit equipped with a 7.5 MHz linear transducer and a 7.5 MHz linear transducer and a Hitachi 415 EUB applied. Primary retinal ablation was diagnosed in 27 cases, and in 14 cases retinal ablation was caused by a proliferative process. In 18 cases a different pathology was demonstrated including 6 patients in whom we detected an intraocular foreign body.

Subtherapeutic doses of interleukin-15 augment the antitumor effect of interleukin-12 in a B16F10 melanoma model in mice.

Interleukin-12 (IL-12) is a potent immunoregulatory cytokine that exhibits antitumor activity in many experimental tumor models. In the present study, we investigated the ability of IL-15, a cytokine sharing many functions of IL-2, to modulate antitumor effectiveness of IL-12 against B16F10 melanoma in mice. In a model of locally growing tumor, intratumoral (i.t.) administration of IL-12, in three cycles of five consecutive daily injections (0.1 mug) followed by 2 days of rest, led to considerable delay of tumor development but no curative response was achieved. When combined with IL-12, subtherapeutic doses of IL-15 (0.4 mug) pontentiated the antitumor effects of IL-12 and induced complete tumor regressions in 50% of mice. Similar results were obtained in a model in which tumor-bearing mice were intravenously co-injected with melanoma cells to induce metastases. Combined administration of IL-12 and IL-15 yielded greater antitumor activity than injections of either cytokine alone and resulted in prolonged survival of mice bearing locally growing tumor and metastases. Studies of immunological parameters in mice treated with both IL-12 and IL-15 have shown enhanced NK activity (against YAC-1 cells) in the spleen and stimulation of both NK activity and specific anti-B16F10 cytotoxic effector cells in tumor-draining lymph nodes (LN). The strong antitumor effect of the IL-12 + IL-15 combination correlated with a high serum level of IFN-gamma in the treated mice. Moreover, increased expression of IL-15Ralpha was demonstrated in LN lymphocytes isolated from mice injected with IL-12. This result together with findings of other authors showing enhanced expression of IL-12 receptor by IL-15 [1] suggests that the augmentation of the antitumor effect during the course of IL-12/IL-15-based therapy could result from reciprocal upregulation of receptors by both cytokines and synergistic effects on IFN-gamma induction.

[The place of radionuclide methods in diagnostic imaging of renovascular hypertension]. / Miejsce metod radioizotopowych w diagnostyce obrazowej nadcisnienia tetniczego naczyniowo-nerkowego.

Numerous investigations and tests are used for diagnosis of renovascular hypertension. From many imaging techniques that are applied in radiology and nuclear medicine we selected those which give us high effectiveness in diagnosing a renal artery stenosis. Choosing from the range of radiological methods we focused on ultrasonography with the "color doppler" and "power doppler" option, renal arteriography and magnetic resonance angiography. Nuclear medicine offers us renal scintigraphy and its modification--renal scintigraphy with the administration of captopril. The high sensitivity of renal scintigraphy with the use of captopril incapables us to detect a stenosis of haemodynamic significance. This is of essential value for planning surgical revascularisation procedures.

Effective chemo-immunotherapy of L1210 leukemia in vivo using interleukin-12 combined with doxorubicin but not with cyclophosphamide, paclitaxel or cisplatin.

It has been well established that chemo-immunotherapy using cytotoxic drugs and appropriate cytokines offers a new approach to increasing the therapeutic index in the treatment of neoplastic diseases. This study investigates the efficacy of combinations of interleukin-12 with cyclophosphamide, paclitaxel, cisplatin or doxorubicin in the murine L1210 leukemia model. Mice inoculated i.p. with 1 x 10(3) or 1 x 10(5) leukemia cells were treated with interleukin-12 and/or chemotherapeutics, and were observed daily for survival. Immunosuppression with X-irradiation or macrophage depletion with injections of silica were used to examine the dependence of the therapeutic effects on the efficiency of the immune system. Treatment with interleukin-12 or one of the studied chemotherapeutics given alone resulted in moderate antileukemic effects. Combination of interleukin-12 with cyclophosphamide or paclitaxel produced no augmentation of anti-leukemic effects in comparison with these agents given alone. Combination of interleukin-12 with cisplatin resulted in prolongation of the survival time; however, in the experiment with mice inoculated with 1 x 10(5) leukemia cells, no long-term survivors (>60 days) were observed; on the contrary, combination of interleukin-12 with doxorubicin resulted in 100% long-term survivors. This effect was completely abrogated either by X-irradiation of mice or by macrophage depletion. We also found that doxorubicin augments IL-12-stimulated production of interferon-gamma in vivo. Our observations demonstrating potentiation of the antileukemic effects of the IL-12 and doxorubicin combination suggest that the combined use of these 2 agents could be beneficial in leukemia therapy.

G-CSF prevents the suppression of bone marrow hematopoiesis induced by IL-12 and augments its antitumor activity in a melanoma model in mice.

BACKGROUND: IL-12 has been successfully used in experimental tumor therapy. However, administration of this cytokine induces dose-dependent suppression of hematopoiesis that could potentially limit its use in clinical trials. We decided to examine whether the myelosuppressive activity of IL-12 could be corrected by the administration of G-CSF. MATERIALS AND METHODS: In the initial experiments the influence of IL-12 and/or G-CSF on bone marrow and spleen GM-CFC was evaluated. To examine whether C-CSF could influence the antitumor activity of IL-12 the combination therapy with these agents was carried out starting on day seven following inoculation of melanoma MmB16 cells into the footpads of B6D2F1 mice. To obtain insight into the mechanism of the observed augmented antitumor activity of the combination therapy with IL-12 and G-CSF, the influence of these cytokines on macrophage activity (cytotoxicity and nitric oxide release) was analyzed. RESULTS: In accord with our expectations, the application of G-CSF partially prevented the suppression of bone marrow myelopoiesis in IL-12 treated mice. Unexpectedly, G-CSF also showed potentiation of antitumor effects of IL-12 in this melanoma model. The augmented antitumor activity of combined IL-12/G-CSF immunotherapy could result from the enhanced stimulation of macrophage NO production and cytotoxicity. CONCLUSION: The simultaneous administration of IL-12 and G-CSF partially prevented suppression of bone marrow myelopoiesis in IL-12-treated mice. Moreover, treatment with these cytokines also results in potentiated antitumor effects in a murine melanoma model.

Granulocyte-macrophage colony-stimulating factor potentiates antitumor activity of interleukin-12 in melanoma model in mice.

To study the antitumor activity of the combination immunotherapy with interleukin-12 (IL-12) and granulocyte-macrophage colony-stimulating factor (GM-CSF), a murine MmB 16 melanoma tumor model was used. Seven days after inoculation of MmB 16 melanoma cells into the footpad of the right hind limb, mice were treated with IL-12 and/or GM-CSF administered intratumorally for 7 consecutive days. IL-12 used both at a high (1 microg) and at a low (0.01 microg) dose per day produced retardation of tumor growth, although neither treatment resulted in any significant prolongation of the survival of tumor-bearing mice. GM-CSF did not by itself exert antitumor activity in this model; however, it potentiated antitumor effects of IL-12. In particular, survival of tumor-bearing mice treated with IL-12 (0.01 microg per day) and GM-CSF was significantly prolonged compared with that in mice treated with either IL-12 or GM-CSF alone.