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G Mariani

Publications and source records attributed to G Mariani.

At least 127 records · Page 7Linked to original sources
PubMed1998

[Locally advanced breast tumors. Role of magnetic resonance in the assessment of response to preoperative therapy and of neoplastic residue before the operation].

INTRODUCTION AND PURPOSE: Induction chemotherapy is the preoperative treatment for locally advanced breast carcinoma. The patients affected with this kind of tumor were previously considered inoperable. The sequential use of different cytotoxic drugs reduces the tumor mass effectively, thus allowing resection and improving patients prognosis. Tumor debulking is at times so significant that conservative treatment can even be considered. A reliable assessment of the response to drug therapy by conventional diagnostic procedures is usually hindered by chemotherapy-induced fibrosis. Magnetic resonance imaging (MRI) is a better tool for distinguishing fibrosis from still vascularized pathologic tissue and thus permits more accurate evaluation of tumor response to chemotherapy, namely tumor debulking and residual viability. MATERIAL AND METHODS: We selected 27 patients with breast cancer and submitted them to MRI both before and after chemotherapy. All examinations were performed with a high field system using 3D Flash sequences with optimized spatial and temporal resolution. RESULTS AND DISCUSSION: The morphologic and dynamic parameters of MRI were in agreement with pathologic findings. In case of persistent disease after chemotherapy, MRI demonstrated increased contrast agent uptake at restaging, with dynamic curves indicating early and intense uptake. In case of marked post-chemotherapy changes, the dynamic curves had a shorter and less steep trend. Finally, when no or very little (few microns) tumor tissue was left, MRI showed no uptake. CONCLUSIONS: Our initial experience indicates MRI as a valid too for monitoring chemotherapy response in breast cancer patients.

Adult↗
PubMed1998

Molecular and clinical aspects of factor VII deficiency.

Factor VII (FVII) plays an important role in the initiation of blood coagulation, forming a complex with tissue factor (TF) which activates FIX and FX and FVII zymogen. FVII deficiency displays considerable phenotypic and molecular heterogeneity and there are inconsistencies between the clinical picture observed and the underlying clotting and molecular defects. We have reviewed the data available in the literature on FVII-deficient patients. Clinically, cases range from asymptomatic to patients with severe haemorrhagic tendencies. Asymptomatic patients typically have FVII activity levels of >20% and are heterozygotes, double heterozygotes or homozygotes. Mild FVII-deficient patients, with FVII activity levels >2%, may be double heterozygotes or homozygotes for FVII gene missense mutations. Undetectable FVII levels in severely affected patients are often due to severe gene defects such as frameshifts or mutations affecting the splice sites. The analysis of structure-function relationships in FVII deficiency is difficult due to the complexity of the interactions involving FVII. Also, assays using different reagents may give different results with a given plasma sample, and are not very accurate at low levels of FVII which, although relatively low, may be clinically significant, adding complexity to the analysis of FVII deficiency. The sensitivity of our methods for phenotypic evaluation of FVII deficiency remains inadequate.

Factor VII Deficiency↗
PubMed1997

Tumor targeting potential of the monoclonal antibody BC-1 against oncofetal fibronectin in nude mice bearing human tumor implants.

BACKGROUND: The immunoglobulin G1 (IgG1) monoclonal antibody (MoAb) BC-1 detects human oncofetal fibronectin, which has extremely restricted distribution in normal adult tissues and is highly expressed in fetal and tumor tissues. METHODS: We studied the biodistribution of 125I-labeled MoAb BC-1 in nude mice bearing subcutaneous human tumor implants of U87MG high-grade astrocytoma and SKMel28 melanoma. 125I-BC-1 was injected either intraperitoneally (i.p.) or intravenously (i.v.), and biodistribution was measured up to 144 hours after injection. In animals bearing SKMel28 implants, tumor targeting was also evaluated by in vivo imaging of the whole mouse by using a dedicated device based on transmitted light excitation after i.v. injection of MoAb BC-1 conjugated with the infrared fluorophore, CY7-bis(N-hydroxy-succinimido)-ester. RESULTS: 125I-BC-1 showed favorable uptake in the human tumor implants, reaching a maximum of 5.27 +/- 0.48% ID/g in the U87MG astrocytoma (72 hours after i.p. injection). The highest uptake in the SKMel28 melanoma implants was 3.49 +/- 0.25% ID/g (24 hours after i.v. injection). Microautoradiography of tumor specimens obtained after administration of 125I-BC-1 clearly showed radioactivity uptake within the two tumors replicating the same pattern of distribution as that of the oncofetal fibronectin shown by immunohistochemistry with MoAb BC-1. Nonspecific uptake of 125I-BC-1 in the bone marrow and skeletal muscle was much lower than in the tumors. In vivo imaging with the fluorophore-labeled MoAb clearly visualized the tumor implants 72-120 hours after i.v. injection. CONCLUSIONS: The experimental results obtained in this study demonstrate the favorable tumor targeting potential in vivo of the radiolabeled MoAb BC-1, a useful marker of neo angiogenesis induced by cancer.

Animals↗
PubMed1997

A pilot pharmacokinetic and immunoscintigraphic study with the technetium-99m-labeled monoclonal antibody BC-1 directed against oncofetal fibronectin in patients with brain tumors.

BACKGROUND: Preliminary experiments in an animal model have shown the favorable tumor targeting potential in vivo of radiolabeled BC-1, an immunoglobulin (Ig)G1 monoclonal antibody (MoAb) that recognizes the human fibronectin isoform (B+) containing the ED-B oncofetal domain. This antigen has extremely restricted distribution in normal adult tissues. Instead, it is highly expressed in fetal and tumor tissues, especially in high grade astrocytomas and malignant gliomas of the brain, in which the process of neoangiogenesis linked to tumor growth is particularly important. METHODS: This study was carried out with five patients who had malignant brain tumors (four gliomas and one malignant angioblastic meningioma). The BC-1 MoAb was labeled with technetium-99m (99mTc) by MDP transchelation. Planar and single photon emission computed tomography (SPECT) imaging was acquired at 4-6 and 20 hours after intravenous injection of about 450 MBq/0.2 mg 99mTc-BC-1 and was compared with the nonspecific indicator of blood-brain barrier disruption, 99mTc-diethylenetriamine pentaacetic acid (DTPA). Plasma pharmacokinetic analysis was based on serial blood sampling. All patients underwent potentially curative surgery at the end of the study. RESULTS: The plasma clearance curves were biexponential, with average T(1/2) values of 2-4 hours and 28-33 hours, respectively. 99mTc-BC-1 showed very low nonspecific uptake in the bone marrow, liver, and spleen. Planar and SPECT imaging with 99mTc-BC-1 visualized brain tumors in all patients, with a pattern of intratumor distribution that specifically identified areas of peripheral tumor growth more accurately than the nonspecific indicator, 99mTc-DTPA. Tumor uptake of 99mTc-BC-1 was correlated with the expression of the specific oncofetal fibronectin, as shown by immunohistochemistry on surgical samples. CONCLUSIONS: These results indicate the diagnostic potential of MoAb 99mTc-BC-1 for immunoscintigraphy in cancer patients, at least when neoangiogenesis induced by cancer is particularly important.

Adult↗
PubMed1997

Direct inhibitory effect of uremic toxins and polyamines on proliferation of VERO culture cells.

The dialysate fluid of uremic patients exhibits, in vitro, an inhibitory effect on cell growth, owing to urea, guanidino compounds, and substances named middle molecules. The polyamines are compounds which exhibit high levels in biological fluids during either normal development or disease such as psoriasis, uremia, and tumors. Dialysate and middle molecules show toxicity and degeneration of the organotype cultures, whereas the free polyamines and nonrecirculated dialysate do not have any toxic effect. The aim of this study is to analyze the effects of polyamines, nonrecirculated dialysate, and middle molecules of uremic patients in periodic hemodialysis on cultured VERO (fibroblast-like cells) growth. These cells show an inhibition of growth in middle molecules or 2 x 10(-4) M putrescine and a stimulation with nonrecirculated dialysate and 2 x 10(-8) M putrescine. The effect is different because the cultures with middle molecules begin growth again after 24 hr, whereas in the presence of 2 x 10(-4) M putrescine no further growth is observed. Cells maintained in middle molecules + 2 x 10(-8) M putrescine show an irreversible degeneration, attesting a toxic effect due to the low molarities of putrescine. The electron microscopy shows alteration of cytoplasmic, mitochondrial, and nuclear membranes, but no chromatin fragmentation with either middle molecules or 2 x 10(-4) M putrescine: this suggests that the cells do not die of apoptosis. In conclusion, during uremia the polyamines could cause toxic effects, even at low concentrations, on cells stressed by other toxic stimuli.

Animals↗
PubMed1997

Absorption and distribution kinetics of the major Parietaria judaica allergen (Par j 1) administered by noninjectable routes in healthy human beings.

BACKGROUND AND OBJECTIVE: The clinical effectiveness of noninjectable routes for specific immunotherapy has been demonstrated in many studies, but no data are available on the kinetics of allergens administered by these routes. Therefore we studied the kinetics of the radiolabeled purified major Parietaria judaica allergen (Par j 1) after sublingual, oral, and intranasal administration to healthy human beings. METHODS: After tracer administration (10 to 12.5 microg of Par j 1 labeled with iodine 123) to nonallergic volunteers, scintigraphic images were recorded at various times. Blood samples were also obtained at serial intervals to evaluate the absorption and distribution of radioactivity in plasma and to identify circulating radioactive species by molecular exclusion gel chromatography. RESULTS: When the sublingual route was used, no circulating radioactivity was detected until the tracer was kept under the tongue. The labeled allergen was rapidly degraded and absorbed in the gastrointestinal tract after swallowing. Plasma radioactivity peaked at about 1.5 to 3 hours and was mostly represented by free radioiodine and small radiolabeled peptides. Some activity not caused by free 123I remained associated with the oral mucosa up to 18 to 20 hours after administration. When the oral route was used, the results were similar to those observed after swallowing the sublingually administered allergen but without any persistence of the tracer in the mouth. When the intranasal route was used, the pattern of plasma radioactivity mimicked that of the sublingual and oral routes, with absorption of activity from the radiolabeled allergen occurring in the gastrointestinal tract after transport to the pharynx by mucociliary clearance. A relevant fraction of the tracer was retained on the nasal mucosa up to 48 hours after administration. CONCLUSION: The data in this study provide the first experimental basis for exploring the in vivo kinetics of allergen administered through noninjectable routes for specific immunotherapy in human beings.

Abdomen↗
PubMed1997

Contribution of factor VII genotype to activated FVII levels. Differences in genotype frequencies between northern and southern European populations.

The relationship between coagulation factor VII (FVII) levels in plasma and FVII genotypes, determined by three polymorphisms (5'F7, IVS7, and 353R/Q), were studied in 500 control subjects enrolled in European multicenter study. The selection of particular FVII genotypes and the analysis of variance clearly indicated the independent contribution of a single 5'F7 insertion (A2) or 353Q (M2) allele to lowering plasma levels of activated FVII (FVIIa) (by a mean 25%). The M2 allele alone was found to make a major contribution to the genetically determined component of the FVIIa levels. Genotypes associated with low FVII levels were significantly rarer in the northern part of Europe (Oslo) than in the southern part (Rome, Murcia). The contribution made by the FVII genotype to the total variance of FVIIa levels was higher (30%) than that made to either FVII activity (25%) or FVII antigen (12%). Subjects with different FVII genotypes showed up to fivefold differences in mean FVIIa values, thus allowing attribution of a substantial part of the considerable interindividual variation to genetic variation, which may be of assistance in the interpretation of FVIIa levels on an individual basis. When FVII levels were adjusted by age and by triglyceride levels, the contribution of FVII genotypes to the FVII phenotypic variance was virtually unchanged. Taken together, these data indicate that in healthy control subjects the FVII genotype is a major predictor of plasma FVIIa levels and would support further study on the role of FVII genetic components in the development of cardiovascular disease.

Adult↗
PubMed1997

[The role of T2*-weighted gradient-echo magnetic resonance sequences in the study of suspected dorsal-lumbosacral vertebral metastases].

INTRODUCTION: Magnetic resonance (MR) imaging showed high reliability in detecting spine metastases with spin-echo (SE) sequences, T1-weighted sequences being generally more sensitive than T/-weighted ones. We investigated the value of T2*-weighted gradient-echo (GE) sequences in studying spine metastases. MATERIALS AND METHODS: Twenty patients with established diagnosis of primary carcinoma and clinically suspected thoracic and/or lumbosacral spine metastases underwent .5-T MR imaging and 99mTc-HDP bone scan. The disagreement of GET2*- versus SET2-weighted images as well as versus bone scan and the disagreement of total MR results versus bone scan results were evaluated by McNemar test. The agreement of GET2*- versus SET1-weighted images was evaluated by Cohen's kappa. RESULTS: Of a total of 111 MR signal abnormalities consistent with metastasis, 109 (98.2%) were T2*-hyperintense, whereas only 50 (45.1%) were T2-hyperintense (p < .0001) and 51 (45.9%) were detected with bone scan (p < .0001). Of a total of 121 MR and/or bone scan findings consistent with metastasis, 111 (91.7%) were MR positive, with high disagreement with 61 (50.4%) positive at bone scan (p < .00001). T2*-hyperintensity associated with T1-hypointensity (with or without T2-hyperintensity) was the most frequent pattern (104/111), 93.7%). CONCLUSIONS: T2*-weighted GE sequences seem to be more effective than T2-weighted SE sequences and as effective as T1-weighted SE sequences. MR imaging confirms its ability in detecting abnormalities consistent with spine metastases.

Adult↗
PubMed1996

Expression of growth factor receptors in unilineage differentiation culture of purified hematopoietic progenitors.

We have evaluated the expression of growth factor receptors (GFRs) on early hematopoietic progenitor cells (HPCs) purified from human adult peripheral blood and induced in liquid suspension culture to unilineage differentiation/maturation through the erythroid (E), granulocytic (G), megakaryocytic (Mk), or monocytic (Mo) lineage. The receptors for basic fibroblast GF (bFGF), erythropoietin (Epo), thrombopoietin (Tpo), and macrophage colony-stimulating factor (MCSF) have been only assayed at mRNA level; the majority of GFRs have been evaluated by both mRNA and protein analyses: the expression patterns were consistent at both levels. In quiescent HPCs the receptors for early-acting [flt3 ligand (FL), c-kit ligand (KL), bFGF, interleukin-6 (IL-6)] and multilineage [IL-3, granulocyte-macrophage CSF (GM-CSF)] HGFs are expressed at significant levels but with different patterns, eg, kit and flt3 are detected on a majority and minority of HPCs, respectively, whereas IL-3Rs and GM-CSFRs are present on almost all HPCs. In the four differentiation pathways, expression of early-acting receptors shows a progressive decrease, more rapidly for bFGFR-1 and flt3 than for c-kit; furthermore, c-kit is more slowly downmodulated in the E and Mk than the G and Mo lineages. As a partial exception, IL-6Rs are still detected through the early or late stages of maturation in the Mk and Mo lineages, respectively. IL-3R expression is progressively and rapidly downmodulated in both E and Mk pathways, whereas it moderately decreases in the Mo lineage and is sustained in the G series. The expression of GM-CSFR is gradually downmodulated in all differentiation pathways, ie, the receptor density markedly decreases but late erythroblasts are still partially GM-CSFR+ and terminal G, Mk and Mo cells are essentially GM-CSFR+. Expression of receptors for late-acting cytokines is lineage-specific. Thus, EpoR, G-CSFR, TpoR, and M-CSFR exhibit a gradual induction followed by a sustained expression in the E, G, MK, and Mo lineages, respectively. In the other differentiation pathways the expression of these receptors is either absent or initially low and there-after suppressed. These observations are compatible with the following multi-step model. (1) The early-acting GFRs are expressed on quiescent HPCs with different patterns, whereas the multilineage GFRs are present on > or = 90% to 95% HPCs. (2) Multilineage GFs, potentiated by early-acting HGFs, trigger HPCs into cycling. HPC proliferation/differentiation is followed by declining expression of the early-acting GFRs and in part of multilineage GFRs (see above). (3) Multilineage GFs trigger the expression of the unilineage GFRs (see Testa U, et al: Blood 81:1442, 1993). Interaction of each unilineage GF with its receptor leads to sustained expression of the receptor (possibly via transcription factors activating the receptor promoter) and thus mediates differentiation/maturation through the pertinent lineage.

Adult↗
PubMed1996

Increased fetal loss in women with heritable thrombophilia.

BACKGROUND: A successful outcome of pregnancy requires an efficient uteroplacental vascular system. Since this system may be compromised by disorders of haemostasis associated with a prothrombotic state, we postulated that maternal thrombophilia might be a risk factor for fetal loss. We studied the relation between heritable thrombophilic defects and fetal loss in a cohort of women with factor V Leiden or deficiency of antithrombin, protein C, or protein S. METHODS: We studied 1384 women enrolled in the European Prospective Cohort on Thrombophilia (EPCOT). Of 843 women with thrombophilia 571 had 1524 pregnancies; of 541 control women 395 had 1019 pregnancies. The controls were partners of male members of the EPCOT cohort or acquaintances of cases. We analysed the frequencies of miscarriage (fetal loss at or before 28 weeks of gestation) and stillbirth (fetal loss after 28 weeks of gestation) jointly and separately. FINDINGS: The risk of fetal loss was increased in women with thrombophilia (168/571 vs 93/395; odds ratio 1.35 [95% Cl 1.01-1.82]). The odds ratio was higher for stillbirth than for miscarriage (3.6 [1.4-9.4] vs 1.27 [0.94-1.71]). The highest odds ratio for stillbirth was in women with combined defects (14.3 [2.4-86.0]) compared with 5.2 (1.5-18.1) in antithrombin deficiency, 2.3 (0.6-8.3) in protein-C deficiency, 3.3 (1.0-11.3) in protein-S deficiency, and 2.0 (0.5-7.7) with factor V Leiden. The corresponding odds ratios for miscarriage in these subgroups were 0.8 (0.2-3.6), 1.7 (1.0-2.8), 1.4 (0.9-2.2), 1.2 (0.7-1.9), and 0.9 (0.5-1.5). Significantly more pregnancy terminations had been done in women with thrombophilia than in controls (odds ratio 2.9 [1.8-4.8]); this discrepancy was apparent in nine of 11 participating centres and for all thrombophilia subgroups. INTERPRETATION: Women with familial thrombophilia, especially those with combined defects or antithrombin deficiency, have an increased risk of fetal loss, particularly stillbirth. Our findings have important implications for therapy and provide a rationale for clinical trials of thromboprophylaxis for affected women with recurrent fetal loss.

Abortion, Spontaneous↗
PubMed1996

Antiphospholipid-protein antibodies are not an uncommon feature in retinal venous occlusions.

The Primary Antiphospholipid Protein Syndrome (PAPS) is characterised by venous and/or arterial thromboses and recurrent foetal loss, in the presence of the Lupus Anticoagulant (LA), elevated antibodies to cardiolipin (ACA) or both. This investigation evaluates the relation between the PAPS and Retinal Vein Occlusion (RVO). Forty-eight consecutive patients with RVO were screened for ACA and LA. PAPS was present in 16 (33%) of the patients. Our results suggest that testing Antiphospholipid-Protein Antibodies (APA) may be useful in these patients, together with the assessment of other vascular risk factors.

Adult↗
PubMed1996

Scintigraphic findings on 99mTc-MDP, 99mTc-sestamibi and 99mTc-HMPAO images in Gaucher's disease.

Gaucher s disease is an autosomal recessive lysosomal storage disease characterized by the specific deficiency of glucocerebrosidase that leads to accumulation of insoluble glucocerebroside in the reticuloendothelial system, particularly the bone marrow, liver, spleen and lymph nodes. Direct scintigraphic visualization of lipid deposits in Gaucher s disease has recently been described, based on the use of the lipid-soluble xenon-133. We report here on the use of the lipophilic cationic complex technetium-99m sestamibi (99mTc-MIBI), employed as an indicator of increased cellular density and metabolic activity, to evaluate Gaucher cell infiltrates in the bone marrow; 99mTc-hexametazime (99mTc-HMPAO) was also employed, as a pure indicator of lipidic infiltration in the bone marrow. A 67-year-old patient with known type 1 Gaucher s disease presented with a painful left hip and knee and difficulty in gait subsequent to traumatic fracture of the left femoral neck that had required implant of a fixation screw-plaque. Bone scan with 99mTc-methylene diphosphonate revealed reduced uptake at the distal metaphyseal-epiphyseal femoral region. In addition, whole-body maps and spot-view acquisitions of the thighs and legs were recorded at both 30 min and 2.5 h after the injection of 99mTc-MIBI: the scintigraphic pattern clearly showed increased uptake at several sites involved by Gaucher deposits in the bone marrow (both knees, with variable intensity in different areas), matching the bone changes detected by conventional x-ray. The target to non-target ratios slowly decreased with time, from an average value of 2.25 in the early scan to an average value of 2 in the delayed scan. The lipid-soluble agent 99mTc-HMPAO exhibited a superimposable scintigraphic pattern of accumulation at the involved sites, though with lower target to non-target ratios (1.27-1.48). The results obtained in this patient suggest a potential role of 99mTc-MIBI in the scintigraphic evaluation of Gaucher s lipid deposits in the bone marrow. If the results are confirmed in other patients, this radiopharmaceutical would offer clear advantages over 133Xe because of its wider availability and greater practicality (i.v. administration of 99mTc-MIBI versus inhalation of 133Xe, and use of a single gamma camera instead of two as with 133Xe).

Aged↗
PubMed1996

The role of nitric oxide in the treatment of neonatal pulmonary hypertension.

Nitric oxide production appears to be decreased in infants with persistent pulmonary hypertension (PPHN). Inhaled nitric oxide may improve oxygenation by two mechanisms: increased pulmonary blood flow and improved ventilation-perfusion matching. Nitric oxide inhalation has been tested in newborns with PPHN, congenital heart diseases, and bronchopulmonary dysplasia. We present a review of the articles concerning inhaled nitric oxide for infants with PPHN. Overall, 59% of the neonates had an initial improvement in oxygenation in response to nitric oxide inhalation. A sustained response was observed in 60% of the infants. Patients with extrapulmonary shunting, clear chest radiographs, and adequate lung volume seem to have a better response, whereas patients with congenital diaphragmatic hernia, severe sepsis, and alveolar capillary dysplasia are more likely to fail. To define the benefit-risk ratio, six prospective randomized trials are currently in progress.

Animals↗
PubMed1996

Ultrastructural and histochemical features of the ground substance in cyclosporin A-induced gingival overgrowth.

The overgrowth-affected gingiva of patients treated with cyclosporin A after kidney transplant was examined with ultrastructural and histochemical methods to evaluate the involvement of connective tissue. Gingival overgrowth has the same clinical signs as local edema. The ultrastructural study showed that the dimensional increase was largely due to increased production of amorphous ground substance by fibroblasts, possibly resulting from an increased release of histamine by mast cells. The histochemical data revealed that the affected tissues contained higher levels of glycosaminoglycans and that cyclosporin A induced comparably high levels of glycosaminoglycans in in vitro cultures of fibroblasts obtained from normal gingiva. The combination of ultrastructural and histochemical data, therefore, strongly suggests that the response of the connective tissue in gingival overgrowth cannot be ignored and may be the main cause of the observed pathological condition.

Alcian Blue↗
PubMed1996

Biochemical modulation by 5-fluorouracil and 1-folinic acid of tumor uptake of intra-arterial 5-[123I]iodo-2'deoxyuridine in patients with liver metastases from colorectal cancer.

In previous studies we demonstrated a high tumor-targeting value of the 123I-labeled thymidine analogue 5-iodo-2'-deoxyuridine (IUdR) infused intra-arterially in patients with liver metastases from colorectal cancer. In the present study we have explored the possibility of enhancing tumor uptake of [123I]IUdR, by biochemical modulation with 5-fluorouracil (5-FU) and 1-folinic acid (FA), a drug combination known to inhibit thymidylate synthetase in tumor cells. The investigation was carried out employing diagnostic imaging doses of [123I]IUdR, much lower than possible therapeutic levels. In the baseline study, [123I]IUdR was infused into the hepatic artery of patients with inoperable liver metastases from colorectal cancer, and a second infusion was performed one week later, after intra-arterial administration of 5-FU and FA. The effect was evaluated by comparing tumor uptake of [123I]IUdR in the second study with that of the baseline study. The average tumor uptake immediately after [123I]IUdR infusion was 9.1% ID in the baseline study, increasing to 14.9% ID after pretreatment with 5-FU and FA. The average enhancement in early tumor uptake of [123I]IUdR induced by biochemical modulation was 72%. This enhancement was sustained at 18 and 42 hours after infusion (stable uptake). The results encourage the pretreatment of patients with 5-FU and FA prior to radioiodinated IUdR administration and suggest its inclusion in therapeutic protocols employing IUdR labeled with 123I or 125I as a source of highly cytotoxic Auger electrons.

Aged↗
PubMed1996

Factor VII gene polymorphisms contribute about one third of the factor VII level variation in plasma.

To assess the role of genetic variation in determining factor VII (FVII) activity and antigen levels we studied a polymorphism located in the 5' region of the gene (5'F7), an intronic mutation (IVS7), and the 353Arg-Gln polymorphism. All the polymorphisms, which showed strong allelic association, analyzed separately or in combination by the one-way analysis of variance, were associated with significantly different FVII levels. The 5'F7 and 353Arg-Gln polymorphic systems, which have very similar allele frequencies, contributed to a similar extent to the total phenotypic variance, whereas the contribution of the IVS7 polymorphism was lower. Genetic variation at the FVII locus, evaluated on combined genotypes, accounted for up to 40% of the phenotype FVII variance. As also shown by the two-way analysis of variance, the use of two out of three markers is advisable, and since the 5'F7 polymorphism can be screened by a simple immunoassay, it should be preferred for population-based studies. No substantial differences between FVII activity and FVII antigen levels were found, thus suggesting that the variation was due to biosynthesis- or stability-mediated mechanisms. The genetic control of FVII levels described in this study plays an important role in determining plasma FVII level variability, which may influence the hemostatic balance.

Adolescent↗
PubMed1996

Tumor uptake and mitotic activity pattern of 5-[125I]iodo-2'- deoxyuridine after intravesical infusion in patients with bladder cancer.

UNLABELLED: In patients with bladder cancer, little is known about diffusion in the tumor mass of 5-iodo-2'-deoxyuridine (IUdR) administered intraluminally, although previous studies based on external scanning have shown promising tumor-targeting properties of IUdR instilled intravesically. This study compared the pattern of IUdR uptake by bladder cancer cells with the actual distribution of mitotic activity, as evaluated by incubation of ex vivo tumor specimens with tritiated thymidine. METHODS: The [125I]IUdR (2-13 MBq) was instilled over 1-3 hr in the bladder of four patients with bladder cancer scheduled for ablative surgery. Twenty-four hours later, surgical samples were assayed for radioactivity and processed for microautoradiography, while fresh tumor specimens were fragmented, incubated with [3H]thymidine and further processed for microautoradiography. The diffusion of labeled IUdR across the bladder wall was evaluated by blood sampling. RESULTS: Tumor incorporation of [125I]IUdR 24 hr after intravesical instillation was 0.002%-0.05% ID/g, while the average tumor-to-normal bladder ratio was about 20. Microautoradiography showed that [125I]IUdR incorporation was confined to tumor cells in the most superficial layers of the bladder, while incubation of the tumor fragments with [3H]thymidine demonstrated the presence of diffuse mitotic activity also in the deeper tumor mass. Diffusion of labeled IUdR in the general circulation was minimal. CONCLUSION: Poor diffusion in the tumor mass makes *IUdR unsuitable for intracavitary therapy of bladder cancer, but the role of such an approach in the postsurgical "sterilization" of cancer remnants floating in the bladder lumen after partial cystectomy should be explored.

Administration, Intravesical↗