Effects of radiolysis on yttrium-90-labeled Lym-1 antibody preparations

An Australian field isolate of Mycoplasma synoviae (MS), 89079/7NS, was exposed to the mutagen N-nitro-N'-methyl-N-nitrosoguanidine. Fifteen clones from the exposed culture were characterized for temperature sensitivity. Four clones labelled B, D, G, and H were temperature sensitive and were further characterized for their ability to colonize chickens and elicit an immune response. Serum antibody responses to MS were detected 3 wk after infection, by eyedrop, in 10 of 10 birds inoculated with 86079/7NS and clones B and G and in 9 of 10 birds inoculated with clone H. No MS antibody response was observed in any bird inoculated with clone D. MS was recovered from the upper trachea of 10 of 10 birds inoculated with clones B, G, and H at 2 wk after infection. No MS was isolated from birds inoculated with clone D. Clone H, designated MS-H, was selected as a potential vaccine candidate.     

Tumour-to-normal uptake ratio of 90Y microspheres in hepatic cancer assessed with 99Tcm macroaggregated albumin

The selective delivery of a high dose of radiation to malignant hepatic tumours by infusion of non-biodegradable yttrium-90 (90Y) microspheres via the hepatic artery while sparing the non-tumorous liver parenchyma depends on the tumour-to-normal uptake ratio (T/N) of the therapeutic radiopharmaceutical. Using intrahepatic arterial technetium-99m macroaggregated albumin (99Tcm-MAA), the effect of tumour type, tumour vascularity assessed by hepatic angiography (HAG), tumour size and the degree of extrahepatic shunting on the T/N was investigated in 377 patients with hepatocellular carcinoma (HCC) and 25 patients with colorectal liver metastases. HCC was shown to have a wider range of T/N (0.2-26.5) compared with liver metastases (2.3-7.2). HCC with vascularity grade 1 on HAG had significantly lower T/N but there was no significant difference in HCC with higher vascularity grades. This confirmed that vascularity on HAG does not predict T/N. Overall there was no correlation between T/N and tumour size. Large tumours (> 20 cm) had a significantly lower T/N, probably due to necrosis in the tumour centres. A decrease in mean T/N with increasing percentages of lung shunting was observed in HCC. Determination of T/N by simulation with 99Tcm-MAA is recommended before internal radiation therapy with 90Y microspheres.     

Continuous infusion chemotherapy as a radiation-enhancing agent for yttrium-90-radiolabeled monoclonal antibody therapy of a human tumor xenograft

The motivation behind the creation of the International Normalized Ratio (INR) was to improve interlaboratory comparison for patients on anticoagulation therapy. In principle, a laboratory that reports the prothrombin time (PT) as an INR can standardize its PT measurements to an international reference thromboplastin. Using probability theory, the authors derived the equation for the probability distribution of the INR based on the PT, the International Sensitivity Index (ISI), and the geometric mean PT of the reference population. With Monte Carlo and numeric integration techniques, the model is validated on data from three different laboratories. The model allows computation of confidence intervals for the INR as a function of PT, ISI, and reference mean. The probabilistic model illustrates that confidence in INR measurements degrades for higher INR values. This occurs primarily as a result of amplification of between-run measurement errors in the PT, which is inherent in the mathematical transformation from the PT to the INR. The probabilistic model can be used by any laboratory to study the reliability of its own INR for any measured PT. This framework provides better insight into the problems of monitoring oral anticoagulation.     

Magnetic resonance imaging features of pituitary yttrium-90 rod implantation

Intersellar implantation of yttrium-90 rods was a common treatment for a variety of pituitary tumours in the 1960s and 1970s. The magnetic resonance (MR) imaging features in three patients with implants (two for growth hormone-secreting and one for prolactin-secreting pituitary adenomas) are presented: the implants appeared as low signal cylinders with no image distortion, in contradistinction to CT where the implants generate beam hardening and back projection artefacts. Confident evaluation of the pituitary fossa for residential tumour and sequelae of therapy could be made on MR. It is the imaging technique of choice in the follow-up of patients treated with yttrium-90 implants.     

Estimation of shunt flow in coronary-pulmonary fistula by lung perfusion scintigraphy with technetium-99m macroaggregated albumin

The shunt flow from the coronary artery to pulmonary arteries was evaluated in 6 patients with coronary-pulmonary fistula by lung perfusion scintigraphy with technetium-99m macroaggregated albumin. In 2 patients, whose degree of visualization of pulmonary arteries by coronary angiography was relatively high, lung perfusion scintigrams demonstrated the defects at the distal of coronary-pulmonary fistulas.     

Experimental study of internal radiation with yttrium-90 microspheres in the treatment of mouse transplanted hepatoma

The effect of yttrium-90 microspheres in the treatment of mouse transplanted hepatoma H22 was studied. Seventy BALB/C mice with hepatoma H22 were randomly divided into 7 groups (A, B, C, D, E, F, G) and treated respectively with 37, 18.5, 14.8, 11.1, 7.4, 3.7 and 0 MBq/cm3 internal radiation by intratumoral injection of Y-90 microspheres. Dose-dependent therapeutic effects were observed. In group A and B, the tumor growth was markedly retarded and eventually un-palpable. Histological examinations showed complete necrosis of the tumor. In groups C,D, E,F, the tumor growth was also inhibited. However, patchy necrosis could be seen amid apparently normal tumor cells. Only isolated, spotty foci of necrosis were present in the untreated control tumors. The results indicate that a tumor of 1 cm diameter can be effectively treated by internal radiation with 18.5MBq Y-90 microspheres injected into the tumor.     

Preparation of cross-linked human serum albumin labelled with 125I for studies of reticuloendothelial system function

A method is described to prepare a new test substance for reticuloendothelial system (RES) function studies. Glutaraldehyde was used for the cross-linking of human serum albumin. The polymeric product was fractionated by repeated chromatography on Sepharose 6B. Cross-linked material with a particle size of approximately 18 nm, as evidenced by electron microscopy, was pooled and labelled with 125I. The surface charge of the albumin polymers, determined by agarose gel electrophoresis, was not significantly changed compared with that of the original albumin monomer. Cross-linking takes place almost entirely between the epsilon-amino groups of lysine in the albumin molecules, as confirmed by amino acid analysis. Preliminary biological tests on mice indicate that the cross-linked polymers are phagocytosed mainly by RE cells of the liver and spleen. The disappearance rate was similar to that of other RE test substances. Intravenous administration of more than 50 times the usual dose caused no deaths, indicating a very low toxicity. Trace amounts of glutaraldehyde were not detectable by gas chromatography. Judging from these experiments, this new preparation of cross-linked albumin fulfils many of the criteria stated for an ideal RES test substance.     

Technetium-99m-DTPA-galactosyl human serum albumin liver scintigraphy evaluation of regional CT/MRI attenuation/signal intensity differences

Terbinafine is an allylamine antifungal agent widely used to treat dermatophyte onychomycosis and dermatomycoses. We report 10 severe cutaneous adverse reactions associated with terbinafine therapy which required discontinuation of the antifungal agent: erythema multiforme (five patients), erythroderma (one), severe urticaria (one), pityriasis rosea (one) and worsening of pre-existing psoriasis (two patients). The spectrum of cutaneous adverse effects associated with terbinafine therapy is reviewed. Patients should be counselled about discontinuing terbinafine at the onset of a cutaneous eruption and about seeking medical advice about further management.     

Iodothyronine content of human thyroid albumin

Stable thyroid hormones (T4 and T3)1) have been demonstrated in pure albumin isolated from normal human thyroid tissue iodinated in vivo. Five samples of albumin were separated from other thyroid proteins by acrylamide gel electrophoresis. After pronase hydrolysis, the content of Thyroid hormones was measured chemically (T4 + T3) as well as by competitive radioactive measurement (T4) and radioimmunoassay (T3). The purity of the albumin and validity of these measurements were confirmed by different techniques. The synthesis of thyroid hormones is not therefore a property unique to Tg and may occur in albumin. However the amount of iodothyronines in the albumin (average 0.004 residue per molecule) is much less than that found in Tg (0.5 residue per molecule). In the albumin as in Tg the number of hormone residues per molecule is proportional to the number of atoms of iodine. At an equivalent iodine concentration, the albumin seems capable of forming the thyroid hormones as well as Tg. The difference between these two proteins, in their capacity to synthesize thyroid hormones, seems to depend on their capacity for iodination. This difference of iodination does not seem to be linked with the number of tyrosyl residues, but might be related to the position of these residues.     

90W-Ni-Mn合金的制备与性能研究

采用液相烧结工艺制备90W-Ni-Mn合金,研究锰含量对合金相对密度和抗拉强度的影响,并通过扫描电镜(SEM)观察试样断口形貌,利用金相显微镜观察样品显微组织.结果表明,随着锰含量增加,合金的相对密度和抗拉强度均降低,在1280℃保温2 h得到的90W-8Ni-2Mn合金相对密度达97.32%,抗拉强度为702.50 MPa;合金的整体密度和抗拉强度较低,主要是由于锰的化学活性很高,烧结过程中在相界面上易生成Mn的氧化物中间相,导致合金的孔隙度较大,从而降低合金的密度和抗拉强度.     

Assessment of regional sympathetic nerve activity in vasospastic angina: analysis of iodine 123-labeled metaiodobenzylguanidine scintigraphy

Injury of the normal central nervous system is a major concern in the radiotherapy of brain tumors, but the pathogenesis of injury remains poorly understood. Modulation of the production of growth factors is associated with ischemia and traumatic injury in the central nervous system. Ionizing radiation has been shown to induce basic fibroblast growth factor in endothelial cells and in cells of a human breast carcinoma cell line. The inducibility of basic fibroblast growth factor after irradiation and its potential role in the recovery response of the central nervous system led us to investigate the effects of radiation on the expression of this growth factor in primary cultures of normal rat type 1 astrocytes. Astrocyte monolayers were exposed to ionizing radiation (1 to 10 Gy). Northern blot analysis revealed that doses of 2 to 10 Gy markedly reduced the expression of basic fibroblast growth factor as early as 1 h after irradiation, and that it remained below levels in unirradiated cells for at least 24 h. The effect was not associated with astrocyte cytotoxicity, and it appears to have some specificity for basic fibroblast growth factor since the levels of mRNA coding for ciliary neurotrophic factor and glial fibrillary acidic protein were not affected.     

The affinity of human serum albumin for [3H]-digitoxin is dependent on albumin concentration

Binding of [3H]-digitoxin to human serum albumin and human serum was investigated in order to characterize the relationship between binding and albumin concentration. Binding was determined by equilibrium dialysis at 37 degrees, 24 hr was required to reach equilibrium. Volume shift and protein dilution were avoided by adding dextran 70 to the buffer compartment. [3H]-Digitoxin binding both to purified albumin and to normal serum was markedly pH-dependent, the bound/unbound ratio being highly significantly (P < 0.001) inversely correlated to pH in the range 6-8.5. When albumin concentration was increased within the physiological range, the ratio bound/unbound [3H]-digitoxin increased much less than expected from predictions using the law of mass action. Binding saturation experiments revealed that the equilibrium dissociation constant for [3H]-digitoxin was increased at higher albumin concentrations without any decrease in the number of binding sites per albumin molecule. In conclusion, the results strongly indicate that binding estimates in therapeutic monitoring of digitoxin in patients with elevated or reduced albumin concentration should not be based on the law of mass action but on empiric relationships between albumin concentration and binding.     

Effusion cytology of hepatocellular carcinoma with in situ hybridisation for human albumin

While the cytological features of hepatocellular carcinoma on fine needle aspiration cytology are well described, cases of hepatocellular carcinoma with malignant cells in ascitic fluid and their characteristics are not. A patient is described with cirrhosis resulting from chronic hepatitis B virus infection, ascites, and hepatocellular carcinoma diagnosed by effusion cytology. The malignant cells in the effusion were shown to be positive for alpha fetoprotein using immunocytochemistry, and for human albumin using in situ hybridisation, confirming the diagnosis of hepatocellular carcinoma. Further investigations in a terminally ill patient were thus avoided.     

Fractionation of normal human bone marrow on albumin gradients

An investigation involving seven successive was undertaken on several groups of 10 to 14 volunteers, in order to evaluate any drug interaction between the three active components of Optalidon, namely amidopyrine (A), butalbital (B), and caffeine (C). Each component was investigated after oral administration, alone and in combination either with one of the others (i.e. A+B, B+C, C+A) or with both of the others in Optalidon (A+B+C). The plasma concentration and urinary excretion were recorded for each component as a function of time. For amidopyrine, two metabolites, amino-4-antipyrine and acetamino-4-antipyrine, were also measured in the urine. Based on a pharmacokinetic model, the following conclusions can be drawn: a) There is no change in bioavailability due to the combination of the three components in Optalidon in respect to their single administration. Within each study, there is no significant difference between the elimination rate constants, areas under the plasma concentration/time curve and percentage excreted in urine for the three components administered alone or in any combination with the other components of Optalidon. b) Concerning the absorption half-life, there is no change for amidopyrine. Only caffeine and butalbital show a statistically significant interaction in respect to this parameter and, as a consequence, differences in the time and value of the maximal plasma concentration in Optalidon. However, these differences are scarcely of anyl clinical relevance.     

Solvation of human serum albumin in aqueous alkylurea solutions

In order to list the negative emergency laparotomies, the records of 24,494 laparotomies performed from 1950 to 1989 were examined. 211 negative laparotomies were performed over this 40 years period: 49 for abdominal trauma, 42 for supposed intestinal obstruction, 44 for supposed peritonitis or visceral infection, 46 for presumed early post-operative abdominal complications and 30 for gastrointestinal bleeding. Over these 4 decades, the emergency laparotomy rate and negative laparotomy rate remained stable despite changes in the diagnostic tools, in the age of the patients and the frequency of their diseases.     

A regional programme to collect plasma for preparation of human immunoglobulin anti-rabies

We identified over 100 recipients of rabies vaccine (human diploid cell vaccine) and recruited them as plasma donors. Some were plasmapheresed at static centres, others by mobile teams. The operation of these teams is described in detail. No plasma was sent to the Fractionation Centre until the date of vaccination had been checked. Assay results showed that the majority of plasma collected between four and 20 weeks after the second dose of vaccine contained 6 or more IU/ml.     

Review of the regulations on quality control of human albumin

PURPOSE: To assess medical students' perceptions of the ethical environment across four years of medical school. METHOD: In the spring of 1996, the authors distributed a questionnaire to all four classes at the Wake Forest University School of Medicine. The students provided demographic information and information about their exposures to or participation in unethical situations. Results were analyzed using multiple analysis of variance, univariate analysis of variance, Pearson correlation, and cross-tabulations. RESULTS: The response rate was 71%. The students reported that exposures to unethical behavior started early and continued to increase with each year in school. For example, 35% of the first-year students reported observing unethical conduct by residents or attending physicians. This percentage rose to 90% of the fourth-year students. The authors found no significant relationship between demographic variables other than the year in school and the ethical dilemma variables. CONCLUSION: Medical students face perceived ethical dilemmas beginning as early as the first year of medical school. Thus ethics instruction must begin in the freshman year. In addition, there must be changes to the environment in which clinical education is conducted to enhance the positive enculturation of students into the medical profession.