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PubMed1978

Erythropoietin assay: present status of methods, pitfalls, and results in polycythemic disorders.

Mammalian erythropoiesis is regulated primarily by the hormone erythropoietin (ESP). Studies of ESF have provided information about its biochemistry and its role in regulating hemoglobin synthesis. Such studies rely on assays for erythropoietic activity in biological fluid. The assay which has proven most valuable and is used most widely is based upon the incorporation of radioactive iron into newly-formed red cells of polycythemic mice. While this assay has gained wide acceptance, it is expensive, cumbersome, imprecise, and insensitive, capable of reliably detecting no less than 50 milliunits of erythropoietin. Improvements in assay techniques will require new methodology relying primarily on immunologic recognition for the determination of hormone activity. Currently under development and in experimental use are radioimmunoassays and a hemagglutination inhibition assay. While work has progressed in these areas, these assays are not of proven value at present and meaningful physiological correlations have not emerged from their use. Alternatively, assays for hormone activity using suspensions of hematopoietic cells and the measurement of incorporation of radioactive isotopes into hemoglobin have provided both improvement in sensitivity and precision. The disadvantage of these types of assays is that they are sensitive to factors other than ESF and may give misleading information, depending on whether the factors present stimulate or inhibit cellular proliferation and hemoglobin synthesis. While such techniques may provide a temporary solution to some problems associated with assaying ESF for purification or physiological studies, they are not the best answer to the overall problem of hormone detection and characterization. The most important contribution to this field will be the availability of large amounts of highly purified and well-characterized ESF.

DNA↗
PubMed1979

In vitro dissolution of Synthos ceramics in an acellular physiological environment.

"Synthos" (beta-tricalcium phosphate) implants in bone are resorbed and replaced with endogenous bone. This investigation was conducted to study by continuous flow and static system techniques, whether or not resorption of synthos occurs by passive dissolution at 37 degrees C. Calcium and phosphates were released in a time dependent manner from synthos in calcium and phosphate free Tris-Hcl buffer (pH 7.4). Scanning electron micrographs (SEM) of buffer exposed ceramics indicated breakdown of grain structure. In contrast, levels of human plasma calcium and phosphate were not altered by ceramics. Significant amounts of 32p were absorbed by the ceramics in the first hour and 45Ca in the second hour of exposure to plasma containing the radioactive isotopes. Exposure of ceramics to plasma did not alter the levels of plasm isotopes significantly for the remaining duration of the experiment. However, breakdown of grain structure was evident in SEM's of ceramics exposed to plasma. It appears that in an acellular physiological environment, dissolution of synthos is diffusion dependent and is limited to a localized surface exchange phenonmenon.

Blood↗
PubMed1998

Stereotactic brachytherapy for a cystic metastatic brain tumor in the midbrain. Case report.

The authors report a rare case of a cystic metastasis in the midbrain that was successfully treated by brachytherapy following stereotactic biopsy and aspiration of the intratumoral cyst. Stereotactic aspiration of cystic lesions can lead to clinical improvement and brachytherapy prevents cyst recurrence. A 46-year-old man was referred to the authors' institution with a 2-month history of a left hemisensory disturbance and a 1-month history of progressive hemiparesis. Magnetic resonance (MR) imaging revealed a ring-enhancing cystic mass in the midbrain. On the basis of this imaging study, a differential diagnosis that included brainstem abscess, glioma, and metastatic tumor was made. Magnetic resonance imaging-guided stereotactic biopsy and aspiration of the intratumoral cyst were performed, yielding 5 ml of yellowish-white fluid. Histological examination provided a diagnosis of adenocarcinoma. During the surgery, a catheter through which brachytherapy would be delivered was inserted at a predetermined target. The patient's left hemiparesis and sensory disturbance were markedly improved and brachytherapy was begun 2 days postoperatively. Three radioactive isotopes composed of iridium-192 were implanted to irradiate the tumor tissue. The total dose at the tumor periphery was 30 Gy, which was administered over 100 hours. External-beam radiotherapy (20 Gy) was added after completion of the brachytherapy. At discharge from the hospital, the patient was alert and all his neurological symptoms had resolved. Follow-up MR imaging revealed stabilization of the cyst and no recurrence of the tumor. The patient is alive and well 18 months following the brachytherapy. This case suggests that brachytherapy can delay cyst recurrence, suppress tumor growth, and prolong survival in patients with cystic brainstem metastasis.

Biopsy↗
PubMed2001

Sentinel lymph node biopsy in breast cancer.

Sentinel lymph node biopsy techniques have evolved in a short period of time to become a highly accurate method for the pathologic staging of clinically node-negative breast cancers. Multiple single and multi-institutional studies have confirmed a high accuracy of pathologic staging (95-100%) with reasonable false-negative rates (0-15%). The use of vital blue dyes, radioactive isotopes, or a combination of the two are the most commonly employed techniques used for this procedure. Currently, two large prospective randomized Phase III clinical trials supported by the National Cancer Institute are underway, which will define the effectiveness of these techniques as compared to standard axillary dissection in regards to regional disease control and patient survival.

Journal Article↗
PubMed2006

The paradox of histone deacetylase inhibitor-mediated modulation of cellular responses to radiation.

Given the widespread use of radiotherapy in cancer, there has been a longstanding interest in the development of chemical compounds that can modify cellular responses to ionizing radiation. Additionally, recent terrorism threats suggesting attacks with 'dirty bombs' containing combinations of radioactive isotopes with conventional explosives, has increased the interest in compounds that can protect from radiation injury. Histone deacetylase inhibitors represent a new class of compounds that can modulate the effects of radiation. Research with histone deacetylase inhibitors has largely focussed on the consequences of their ability to alter gene transcription via histone acetylation and on their properties as anti-cancer agents. They have been shown to cause cell cycle and growth arrest, differentiation and in certain cases apoptosis in cell cultures and in vivo. In addition to their intrinsic anti-cancer properties, numerous studies have demonstrated that histone deacetylase inhibitors can modulate cellular responses to other toxicity-inducing modalities including ionizing radiation. The consensus is that histone deacetylase inhibitors markedly enhance the sensitivity of cells to radiation by altering numerous molecular pathways. Intriguingly, a report has also shown that histone deacetylase inhibitors can reduce radiation induced acute and late skin damage using a well-established animal model of cutaneous radiation syndrome. Hence, there is an emerging interest in potential use of histone deacetylase inhibitors as radiation sensitizers or protectors. This review focuses on the different mechanisms by which histone deacetylase inhibitors modify cellular responses to ionizing radiation.

Animals↗
PubMed2005

[Research on time-course differential imaging by bone scintigraphy].

The temporal image subtraction technique was applied to bone scintigraphy, using Photoshop (commercially available image processing software) and Morpher (public domain warping software). For the temporal subtraction images, 81 subtraction images (19 cases) were prepared by a method used to subtract the previous images from the current ones. Registration of the current and previous images was performed by manual operation using Photoshop, and warping was done using the warping function of Morpher. In addition, difference images prepared after correcting the distributions of radioactive isotopes of the current and previous images using the count of the pelvic region were also examined. Compared with manual operation, alignment of images by warping improved registration and reduced the generation of pseudo-images of subtraction images. The rate of identification of abnormal accumulation-enhanced regions and subjective evaluation by doctors was improved for warping more than for manual operation. Furthermore, abnormal hot regions, which are difficult to find in film images, could be found in three subtraction images. In addition, it was confirmed that abnormal hot regions become more visible in many cases by preparing subtraction images after correcting the count between images using the count of the pelvic region. Thus, it is suggested that the temporal image subtraction technique in bone scintigraphy enables more accurate observation of enhancement of or changes in abnormal hot regions, which will support diagnostic reading. It is considered that enhancement of or changes in abnormal hot regions will be more accurately understood through further detailed discussion in the future.

Bone and Bones↗
PubMed1983

Biosynthesis of the antitumor antibiotic CC-1065 by Streptomyces zelensis.

The biosynthesis of the antitumor antibiotic, CC-1065, has been investigated by radioactive isotope techniques, in combination with chemical degradation of CC-1065. Tyrosine, dopa, serine and methionine (S-CH3 group) have been shown to be precursors of CC-1065. Tyrosine is proposed to be a precursor of all three benzodipyrrole subunits, while dopa is only apparently incorporated into subunits B and C. Serine is postulated to contribute three 2C units, with loss of C-1, to all three subunits of CC-1065. The S-CH3 group of methionine probably contributes four C-1 units to CC-1065 of which one is incorporated with considerable loss of tritium, most probably into the cyclopropane ring of subunit A.

Antibiotics, Antineoplastic↗
PubMed1976

[Experimental administration of a fatal dose of antiglomerular antibodies].

The administration of a sufficient dose of heterologous antibodies against renal glomeruli in rats produces symptoms of respiratory insufficiency and pulmonary oedema causing death of the animals. Under these experimental conditions the basic pathogenic mechanism appears to be binding of the injected antibodies on the basement membrane structures of pulmonary capillaries resulting in their damage. Such changes are followed by widespread haemorrhagic exsudative changes in the lungs. Localization of the injected antiglomerular antibodies has been studied with the aid of immunohistochemical methods and in addition, by a method using antibodies labelled with radioactive isotopes of iodine, the so-called "paired administration technique". After the administration of a lethal dose of antiglomerular antibodies, they later appeared to be predominantly localized in the lungs. This fact correlates well with the idea of the effect of the antibodies upon pulmonary parenchyma in the present experiment. A remarkable finding was a rather high localization of the injected antibodies in the liver parenchyma which could be explained either by a cross reaction between the antibodies and the antigens of hepatic vascular spaces, or by a shock reaction associated with heart failure and circulatory disturbances.

Animals↗
PubMed1999

[Brachytherapy in choroidal melanoma].

BACKGROUND AND PURPOSE: Brachyterapy in the management of intraocular tumors was introduced in the Department of Ophthalmology in Cracow in the late sixties, soon after it was applied by Stallard. For many years, similar to other oncological centers, we used 60Co and in 1994 we started with 106Ru and at the end of 1997 with 125J. The aim of this paper is to present our experiences with 106Ru and 125J brachytheray in posterior uveal melanoma. MATERIAL AND METHODS: Our studies comprised 164 patients with choroidal melanoma, treated in the years 1995-1997 with 106Ru and 19 patients treated between December 1997 nad April 1998 with 125J plaque brachytherapy. There were 93 women and 90 men, aged 18-86. Tumor thickness was beneath 6 mm in 85 cases, 6-9 mm in 63 and above 9 mm in 35. In 121 eyes anterior margin of the tumor was located in equatorial region or posterior to it, 62 the tumor situated anterior to the equator attached to the ciliary body. The usual dosage was 60-100 Gy to the tumor apex; in 33 eyes transpupillary thermotherapy (TTT) with diode laser was added. The follow-up ranges from 3 months to 3 years after 106Ru plaque brachytherapy and 1-3 months after 125J. RESULTS: Criteria of the treatment efficacy were decrease of tumor thickness at least 10%, increase of its density and vessel obliterations. Among 164 patients treated with 106Ru improvement was achieved in 84 (51.2%) of cases, stabilization in 50 (30.5%) and negative results in 30 (18.3%). Enucleation was performed in 16 (9.7%) cases. Among 19 patients treated with 125J preliminary evaluation indicates positive reaction for treatment in 14 cases. CONCLUSIONS: Our studies confirm the opinion that brachytherapy is a method of choice in the management of many cases of posterior uveal melanoma. There are significant relationships between the results of treatment and the size of tumor and its location. The adequate choice of the kind of radioactive isotope in the plaque is very important.

Adolescent↗
PubMed1999

[A preliminary study on the genetic susceptibility of asthma in a Chinese population].

OBJECTIVE: To study the asthma genetic susceptibility by way of ccandidate region so as to accumulate data on the related loci in Chinese population and determine whether genetic susceptibility to asthma is linked to the chromosome region. METHODS: One hundred ninety-two samples from 32 families were collected from Zhaoan county in Fujian province. Two Rsa I polymorphic sites within uncoded region of the high-affinity IgE receptor beta chain gene (Fc(epsilon) RI-beta) located on chromosome 11q13 were detected by PCR/Rsa I restriction endonuclease digestion. The polymorphic markers D5S436 and D5S393 within chromosome 5q31-33 were amplified by PCR incorporated with radioactive isotope. The asthma family samples were compared with unrelated samples randomly selected from general population. RESULTS: Genotypes containing A allele within intron 2 polymorphic site of Fc(epsilon) RI-beta gene were associated with asthma (P<0.05,OR = 2.039). Significant difference in the level of total serum IgE was noted among three genotypes of intron 2 polymorphic site of Fc(epsilon) RI-beta gene (P<0.05). The association between A allele and elevated total serum IgE was also significant (P<0.05, RR = 1.361). No relationship between exon 7 polymorphic site of Fc epsilonRI-beta gene and asthma was shown. By sib-pair analysis, significant evidence for linkage to asthma was observed with D5S436 (P<0.05) but not with D5S393. No significant linkage to total serum IgE was identified with both of these markers. CONCLUSION: The above-accumulated data suggested that both Fc epsilonRI-beta gene and chromosome 5q31-33 could be very attractive candidate gene and region for further studies in Chinese population, and to confirm these preliminary results, more markers within these regions merit testing in additional population samples.

Adolescent↗
PubMed1975

[A quantitative method for the measurement of the marginal space using Ca45].

A survey of the most known methods of testing for marginal fit is followed by the description of the determination of marginal leakage by means of autoradiography. 45Ca was used as a radioactive isotope. The most favourable times of penetration and exposure are indicated. Provided that certain standards are respected, the magnified autoradiograms may be measured and the values obtained can be used for comparisons. The applicability and the error range of the method were tested in 2 series of Super-Syntrex fillings.

Autoradiography↗
PubMedDate not supplied

Radioimmunoguided surgery.

Although clinical staging of neoplastic diseases has long remained the only approach to prognosis and treatment, parameters for stage determination, such as tumor size (T) and lymph-node involvement (N), do not always provide effective indication of optimal treatment. Molecular medicine has also provided useful indications as to an alternative and/or integration to clinical staging. Despite the numerous possibilities afforded by pre-operative staging techniques, failures in defining the real spread of neoplasias into surrounding structures have remained a very important diagnostic problem. The labeling of monoclonal antibodies binding with neoplastic target cells by way of radioactive isotopes introduced the techniques known as immunoscintigraphy and SPECT, which then evolved into radioimmunoguided surgery. Fourty patients suffering from colorectal cancer whose age ranged between 42-82 years were singled out for this study. Before undergoing surgery, they were administered pancoloscopy and macrobiopsies, AP-LL chest x-rays, hepatobiliary ECT, echoendoscopy, abdomen and pelvis CT with nephrostographic phase, and total body bone scintigraphy. They were treated with 125I-B72.3 and 125I-FO23C5 (5% and 95% of patients, respectively). Thyrosuppression was achieved by Lugol solution (15 drops x 3/die) from the 6th day before infusion and until the day of surgical operation. Radioimmunoguided surgery (RIGS) has also been tested on staging and second-look of ovarian tumors. Five years after surgical operation the survival rate of Dukes A patients (15%) was confirmed to amount to 100%, whereas for Dukes B patients (50%) having undergone RIGS-guided exeresis on single unrecognized metastases (2 patients) and on unrecognized n+ (5 patients) the survival rate was found to be 85% after 5 years; 2 patients deceased due to relapse; 1 patient deceased due to e.p.a. Finally, for Dukes C patients; (35%) having undergone RIGS-guided exeresis on unrecognized liver micrometastases (1 patient), on single isolated metastases (2 patients) and in the occurrence of multicentric lymph-node positivity (9 patients), the survival rate after 5 years was found to amount to 64%; 5 patients deceased due to relapse. Out of 19 patients without pre-operative evidence of ovarian tumor as opposed to just 1 patient suspected of pelvic recurrence, after intra-operative surgical radicalization (45%), 1 patient was diagnosed fibrosis (suspicious lesion on CT) and 1 other patient peritoneal MTS (negative CT) by means of RIGS. RIGS has made it possible: to localize primary and/or metastatic lesions; to determine tumor-free margins, loco-regional disease spread; to differentiate suspicious foci on inspection and palpation (biotopic sampling); to detect invisible and impalpable tumor foci (occult sites); to verify radical exeresis; to evaluate lymphatic drainage stations; to enable guided exeresis of liver metastases.

Adult↗
PubMed1999

Intracoronary brachytherapy: the beginning of the end of restenosis?

Restenosis remains a major problem 20 years after the introduction of coronary angioplasty. Pharmacological therapy has generally been disappointing in reducing the incidence of neointimal hyperplasia. Intracoronary brachytherapy is the latest anti proliferative agent that is showing promise in the fight against restenosis. Radiation therapy has been used for decades in the treatment of benign proliferative disorders. Animal studies have consistently demonstrated the efficacy of radiation therapy in inhibiting neointimal hyperplasia. Clinical trials, using different radioactive isotopes and radiation sources, are now showing dramatic reduction in neointimal hyperplasia and restenosis rates following balloon angioplasty and stenting. Intracoronary brachytherapy is beginning to show promise as one of the truly effective agent against neointimal hyperplasia and restenosis.

Animals↗
PubMed1976

Tetracyclines, doxycycline and calcified tissues.

The use of radioactive isotope techniques has led to a thorough re-assessment of our knowledge of bone histology. It is known that tetracyclines faithfully follow the pattern of calcium metabolism in the body. Fluorescence microscopy, after double labeling with tetracyclines and alizarin red S, is very useful for collection of qualitative and quantitative data on compact and spongy bone remodeling. Two illustrations are presented which demonstrate how oxytetracycline and doxycycline administered in therapeutic doses to growing dogs, become deposited in the dentine. The significance of these findings is discussed.

Animals↗
PubMedDate not supplied

[New administration routes for immunotherapy].

Specific immunotherapy represents the turning point of the treatment of allergic illnesses and this, together with avoiding the allergen, currently constitutes the only etiologic treatment available. When conditions are optimum, which include showing the etiologic importance of the allergen, the availability of quality allergenic extracts and the correct monitoring of the patient, immunotherapy with subcutaneous injections is a safe and efficient treatment. As in any other treatment, subcutaneous immunotherapy is not exempt from possible adverse reactions related to its administration, although when the recommended guidelines are followed, these reactions tend to be predominantly local, of little intensity and easy to control. Over the last 15 years, especially in Europe, there has been an increased interest in the use of local applications, not injections, in immunotherapy and we are looking, above all, to increase the safety and the patients acceptance. The alternative applications to injected immunotherapy that have been studied and used to date are: oral, sublingual, nasal and bronchial. In the World Health Organisation position papers (WHO), from the European Academy of Allergies and Clinical Immunology (EAACI) and the European Society of Paediatric Allergy and Clinical Immunology (ESPACI), bronchial immunotherapy is not recommended, due to the fact that its efficiency is not sufficiently documented and the there is a risk involved with severe side effects of an asthmatic nature. Nasal immunotherapy is not considered to be suitable for clinical use on children and oral immunotherapy is not considered to be suitable for clinical use on children and oral immunotherapy is not recommended, except as part of controlled studies, due to the risk of side effects and insufficient documentation that guarantees the efficiency. Currently, in clinical practice, it apears that a progressive interest has been detected in sublingual immunotherapy and in our country this is being used more and more, which means that the current level of our knowledge on this terapeutical method should be reviewed. In order to consider sublingual immunotherapy as a valid alternative, taking the bassis of its action mechanisms as a starting point, a greater safety in its administration should be checked, its clinical efficiency demonstrated and this efficiency should at least be comparable to that obtained using subcutaneous immunotherapy. The action mechanism of sublingual immunotherapy is unknown. Experiments using allergenic extracts marked with radioactive isotopes administered sublingually do not indicate any absorption through the oral mucous, which is reassuring in the sense that no systematic adverse reactions are feared, but on the other hand we are faced with serious doubts concerning the basis for this type of immunotherapy administration. Sublingual immunotherapy, especially when the treatment is exclusively sublingual (where the dose is subsequently spat out), is a safe treatment according to what can be deduced from the clinical tests and the pharmacovigilance studies published, although the sublingual means of administration with a subsequent ingestion of the dose can give rise to adverse systematic reactions, such as urticaria and asthma. From the experience gained since this method has been used, to date there have been no reported serious systematic reactions that are life threatening. The analysis of the results of the double-blind control clinical tests published to date, lead us to the same conclusion as the WHO, the EAACI and the ESPACI position papers, in the sense that there is not sufficient evidence available to recommend the use of sublingual immunotherapy on children, except when it is part of a controlled study. (ABSTRACT TRUNCATED)

Administration, Intranasal↗
PubMed2000

Spread of epidural blockade in the anaesthetised pig using technetium99 and sensory-evoked potentials.

Our objective was to determine the extension and duration of a stable segmental thoracic or lumbar epidural blockade by lidocaine in the 20 to 25-kg pig. Fourteen anaesthetised pigs were investigated. The radioactive isotope technetium99 (Tc99) was added to lidocaine to evaluate the spread in the epidural space. One ml of this solution was administered via an epidural catheter either at the Th(6-7) or L6-S1 level. Sensory-evoked potentials (SEPs) were measured following peripheral nerve stimulation, to determine duration and sensory extension of the epidural blockade. The thoracic anatomical mean spread was 14.2 vertebrae. The end points of the spread were C3-C7 and Th8-Th13 and the lumbar anatomical mean spread was 10.2 vertebrae. The end points were Th10-Th12 and L6-S1. It was possible to abolish the SEPs with 2 and 4% lidocaine. A smaller volume of lidocaine was needed if a second dose was administered within 20 min. With 4% lidocaine it was possible to abolish the SEPs for more than 180 min. The use of 1 ml of 4% lidocaine repeated after 20 and 60 min at the Th(6-7) or L6-S1 level achieved a stable thoracic or lumbar epidural blockade.

Anesthesia, Epidural↗
PubMed2001

Water and electrolyte homeostasis and kidney function of desert-dwelling marsupial wallabies in Western Australia.

Prolonged drought, necessitating conservation of water, is one of the major environmental challenges faced by many Australian marsupials. Radioactive isotopes of water and sodium were used to assess the ability of two species of marsupial wallabies to maintain water and electrolyte balance during periods of extreme water deprivation in the arid Pilbara region of Western Australia. The spectacled hare-wallaby, Lagorchestes conspicillatus, has the lowest mass-specific rate of water turnover at 27.5 ml.kg(-0.82).day(-1) yet reported for any mammal and was two to three orders of magnitude lower than that of the Rothschild's rock-wallaby, Petrogale rothschildi. Studies of renal function show that the hare-wallaby conserves water by producing a highly concentrated urine under the influence of lysine vasopressin (LVP), the anti-diuretic hormone (ADH) in macropodid marsupials. In contrast, rock-wallabies show unusual renal responses to water deprivation, with no change in LVP levels and a limited response to water deprivation involving a reduction in renal plasma flow and glomerular filtration rate, with no significant change in tubular function. Both species are able to maintain water and electrolyte homeostasis during periods of drought, highlighting the efficacy of their differing adaptive solutions to the problem of water scarcity, although the hare-wallaby is superior to the rock-wallaby in this respect. Rock-wallabies appear to rely primarily on behavioural rather than physiological responses for their survival in the Pilbara and appear to be more vulnerable to extinction in the event of significant habitat modification. The secure nature of their rock habitat, however, means that they have suffered less than hare-wallabies in the recent past.

Animals↗
PubMed1997

Taurine influx in cultured rat cardiomyocytes and changes after CVB3 infection.

Monolayer culture of spontaneously contracting rat heart cells was obtained from newborn SD rats and seeded into culture plates. 100TCID50 of coxsackie virus B3(CVB3) (Nancy strain) was added as the infected group. The dynamics of taurine transport across membrane of normal heart cells and changes after infection were examined by using radioactive isotope tracing techniques. The results demonstrated that: (1) two uptake systems of taurine with different affinities and capacities were present in the plasma membrane of cultured rat cardiomyocytes, the Km of high and low affinity were 9.5 x 10(-5) mol/L and 1.3 x 10(-2) mol/L, respectively; (2) taurine transport across membrane was sodium-dependent with a positive linear relationship between amount of taurine influx and extracellular concentration of sodium; in addition, it was also regulated by osmolarity; (3) beta-alanine, a carboxylic analog of taurine, could inhibit the uptake of taurine in dose-dependently; (4) taurine influx was decreased in cultured rat cardiomyocytes after infected with CVB3. (5) the Inhibition ratio of taurine transport was enhanced as the infected time prolonged. This experiment provides a basis for further investigation of kinetic test of taurine transport and more study should be carried out to learn the effect of taurine in viral myocarditis.

Animals↗