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PubMed2005

Prognosis of hypercalcemia in aerodigestive tract cancers: study of 136 recent cases.

Recent data issuing the prognostic impact of hypercalcemia on outcome of aerodigestive tract cancers are spare. To assess the prognosis and the survival of head and neck cancer patients with hypercalcemia, we reviewed 136 recent successive cases, including also oesophageal and lung cancers. Data were collected from a retrospective database (July 2002-January 2004). Hypercalcemia was defined by calcemia level above 2.55 mmol/l. Univariate analysis for prognosis was performed with Mann-Whitney test (continuous variables) and Odd Ratio with 95% confidence interval (categorical variables). The primary locations were : oropharynx and oral cavity (79, 58%), hypopharynx (13, 9.5%), larynx (10, 7.3%), oesophagus (17, 12.5%) and lung (17, 12.5%). There were 23 females and 123 males, with a median age of 53 (18-86). The incidence of bone metastasis was low: 20/136, 14.5%. At cancer diagnosis, 32 hypercalcemia were observed. With a median follow-up of 88 days (2-553), we observed 98 deaths (overall mortality=72%). The median overall survival was 35 days (2-553+). The pejorative prognostic factors were: male gender (OR=2.64 CI 95% 1.07-6.82), age inferior to 50 (OR=2.67 CI 95% 1.23-5.8), presence of distant metastasis (OR=4.45 CI 95% 1.8-11.01), elevation of alkaline phosphatases (OR=7 CI 95% 2.73-17.9) and need of hospitalization for intravenous hydratation (OR=5.11 CI 95% 1.99-13.17). We observed 39 recurrences of hypercalcemia. The predictive factors for recurrence of hypercalcemia were: age superior to 50 (OR=4.61 CI 95% 2.02-10.52), male gender (OR=38.22 CI 95% 12.2-89), calcemia level superior to 2.7 mmol/l (OR=3.08 CI 95% 1.42-6.64) and absence of diphosphonates (bisphosphonates: OR=2.16 CI 95% 1.01-4.63). Despite use of diphosphonates (infusions of pamidronate), hypercalcemia is associated with very poor prognosis. Tumour location and level of calcemia had no prognostic value.

Adolescent↗
PubMed2006

Quantitative analysis of planar bone scintigraphy in patients with unilateral condylar hyperplasia.

OBJECTIVE: This study compares quantitative analysis of planar bone scintigrams with visual interpretation in patients having unilateral condylar hyperplasia (UCH) and normal control subjects. The possibility of using a bony structure in a region near the condyle as an objective measurement of bone activity is assessed. STUDY DESIGN: Planar bone scintigrams from 20 subjects suspected of having active UCH were analyzed both qualitatively and quantitatively. Bone activity was assessed in both condyles as well as in reference sites in the cervical spine and the skull. Percentile activities for both condyle regions and ratios using condyle activity versus reference regions were assessed. RESULTS: All UCH patients had unilateral increased activity on qualitative visual interpretation of the bone scan. The mean percentile activities of the affected and unaffected condyles in the UCH group were significantly different at 55.3% and 44.7%, respectively (P < .001). No significant difference was found in the control group, with the ratios between left and right condyle being 49.5% and 50.5%, respectively (P = .46). In the ratios between the region of interest (ROI) in the condyles versus the ROIs selected for the cervical spine and the skull, a significant difference was noticed in the UCH group; however, there was a considerable overlap between condyle and reference ROI ratios. Symmetrical uptake of diphosphonate reliably excluded continued asymmetrical growth of the condyles. CONCLUSIONS: Quantitative analysis of planar scintigrams in unilateral condylar hyperplasia patients was not found to be superior to qualitative visual interpretation of the scans. Because of a considerable overlap in condyle/reference ROI ratios, quantified ratios did not seem to be clinically helpful in the differentiation of a hyperplastic condyle from a normal condyle. In the case of unilateral increased condylar uptake of diphosphonate, clinical assessment is mandatory.

Adult↗
PubMed1992

Radiopharmaceuticals for palliation of metastatic osseous lesions: biologic and physical background.

The intimate admixing of bone matrix and bone marrow is a central point in devising therapy of metastatic lesions. Since specific modalities are not yet available for destroying the malignant cells, treatment is usually palliative. The use of stable gallium (Ga-nitrate) and of a diphosphonate (aminohydroxypropylidine diphosphonate disodium) as osteoclast inhibitors is discussed. The marrow, as well as the matrix, can be affected by external radiation. This is also true with bone-seeking radiopharmaceuticals. There is no ideal radiopharmaceutical available for treating metastases in bone, but the characteristics of several presently available (or proposed) are discussed, and possible use of tumor radiation sensitizers or bone marrow protectors is mentioned. Difficulties are also encountered in calculating accurate dosimetry. Clinical experience is needed to determine a reasonable optimal dose with any particular radiopharmaceutical for relief of pain with low bone marrow toxicity.

Bone Neoplasms↗
PubMed1997

Oncologic imaging: interactions of nuclear medicine with CT and MRI using the bone scan as a model.

There are many radionuclides currently used in oncologic imaging including technetium 99m diphosphonates, gallium 67, thallium 201, technetium 99m sestamibi, and others. The specific interactions of each of these agents with computed tomography (CT) and magnetic resonance imaging (MRI) are extensive. The radionuclide bone scan using 99mTc diphosphonate is the most frequently performed nuclear medicine examination in oncologic imaging. The bone scan can be used as a model to generalize the interactions of nuclear medicine with CT and MRI. The applications for the bone scan and many other nuclear medicine procedures in oncologic imaging include evaluating for metastases, assessing the response to therapy, and guiding radiation therapy planning. Bone scan findings that are equivocal for metastases can be evaluated with other imaging modalities. Areas of abnormal uptake in the axial skeleton can be evaluated with CT or MRI, whereas those in the appendicular skeleton can be evaluated with plain radiographs, followed by CT or MRI if necessary. The bone scan is valuable in oncologic imaging because of its high sensitivity for lesion detection, its ease in whole body imaging, and its low cost. The major disadvantage of the bone scan is that it lacks fine anatomic detail, which is of particular importance in the cancer patient with local back pain, radiculopathy, or myelopathy. Because local back pain with or without radiculopathy is the earliest symptom of spinal cord compression in 90% of patients, an MRI is the study of choice because of its exquisite depiction of anatomy. A myelogram followed by a postmyelogram CT can be performed if there are contraindications to an MRI. The basic principle of high sensitivity for lesion detection and ease in whole body imaging provided by nuclear medicine and fine anatomic detail provided by CT and MRI can be applied also to the use of other radionuclides in oncologic imaging.

Bone Neoplasms↗
PubMed1978

The value of radionuclide scanning in early diagnosis of intestinal infarction.

Small focal areas of intestinal infarction were produced experimentally in mice by two techniques: (1) intussusception and (2) suture strangulation of a loop of jejunum. The radionuclide technetium 99m diphosphonate (99mTc-diphosphonate) was subsequently administered intravenously, and abdominal scans were obtained. The scans demonstrated focal infarcted lesions accurately, and every positive scan was associated with an area of infarction, as demonstrated by pathologic examination. However, negative scans did not definitely exclude an area of infarction: in the intussusception study there were five false negative scans in 25 animals, and in the loop ligation study there were two false negative scans in 28 animals. The technique may have clinical application in such intestinal diseases as necrotizing enterocolitis in infancy in which early diagnosis of small areas of necrosis is currently difficult by clinical and radiologic methods.

Animals↗
PubMed1987

Total bone uptake in management of metastatic carcinoma of the prostate.

The status of patients with skeletal metastases from prostatic carcinoma was determined from a quantitative uptake and retention measurement of the bone scanning radiopharmaceutical 99mtechnetium-methylene diphosphonate. Whole body counts were performed 5 minutes and 24 hours after intravenous administration of 99mtechnetium-methylene diphosphonate, and were expressed as the percentage uptake by the skeleton at 24 hours. Skeletal uptake determinations were done in 29 patients with prostatic cancer (17 with osseous metastases) who were evaluated at 3 to 6-month intervals. Group 1 consisted of patients who responded to therapy and achieved remission, group 2 included patients with relapse or progressive disease, group 3 consisted of those with metastases who were in remission for longer than 6 months and group 4 included those without evidence of any bony metastases. The baseline mean +/- standard deviation 24-hour skeletal uptake values were 46.1 +/- 12.0 per cent in group 1, 34.3 +/- 13.9 per cent in group 2, 27.0 +/- 5.9 per cent in group 3 and 28.9 +/- 5.5 per cent in group 4. At 3 to 6 months the values in group 1 (responders) decreased by 18 per cent, while those in group 2 (relapse or progression) increased by 19 per cent and those in group 3 (remission) increased by 1.5 per cent. The quantitative 24-hour skeletal uptake test was performed easily, reproducible and at least as useful as concurrent chemical blood tests and subjective bone scan interpretations.

Acid Phosphatase↗
PubMed2000

Endotoxin-induced aggravation of preservation-reperfusion injury of rat liver and its modulation.

BACKGROUND/AIMS: In clinical transplantation, exposure of donors to gut-derived endotoxin occurs frequently and may adversely affect liver transplantation therapy. The aim of this study was to investigate: 1) whether brief exposure of rats to endotoxin before liver procurement aggravates the early phase of reperfusion injury of hepatic explants; and if so 2) whether Kupffer cell activation is a contributing factor to liver injury; and 3) whether heparin and pentoxifylline could minimize this effect. METHODS: Male Wistar rats were injected with 0.2-4.0 mg/kg of Escherichia coli lipopolysaccharide 2 h prior to liver harvest. After preservation in University of Wisconsin cold-storage solution, the livers were reperfused using a blood-free perfusion model. To inactivate Kupffer cells, some rats were pretreated with gadolinium chloride or liposome-encapsulated dichloromethylene-diphosphonate before lipopolysaccharide administration. The other rats received lipopolysaccharide with heparin or pentoxifylline. RESULTS: In a dose-independent fashion, lipopolysaccharide impaired portal flow during graft reperfusion. In a dose-dependent way, lipopolysaccharide increased lactate dehydrogenase release into the perfusate and decreased bile flow and bromosulfophthalein excretion. Gadolinium chloride, liposomal dichloromethylene-diphosphonate, heparin, and pentoxifylline reduced lactate dehydrogenase release by 34%, 43%, 59%, and 64%, respectively, and improved functional parameters of the liver. A 52-fold increased neutrophil infiltration in the liver sinusoids after lipopolysaccharide exposure was not affected significantly by the drugs studied; however, heparin reduced markedly neutrophil activation. CONCLUSIONS: The results of this investigation provide direct evidence that aggravation of preservation-reperfusion injury of rat liver by endotoxin is mediated by Kupffer cell-dependent mechanism(s) and it can be minimized by heparin and pentoxifylline.

Adenosine↗
PubMed1988

Radionuclide exploration of dialysis amyloidosis: preliminary experience.

The noninvasive diagnosis of amyloid arthropathy in dialysis patients is still uncertain. Therefore, we investigated the potential diagnostic value of the 99mTc-methylene diphosphonate scan in seven long-term hemodialysis patients suffering from chronic joint pain who had biopsy-proven osteoarticular amyloidosis of the recently discovered beta 2-microglobulin (beta 2-M) type. In six, but in none of five control patients on short-term hemodialysis, increased tracer uptake was found at the site of one or several articular and/or periarticular regions. Increased uptake at a given joint was often, but not always, associated with joint pain. It appeared to precede radiologically visible changes. In conclusion, the 99mTc-methylene diphosphonate scan may be of help in the early diagnosis of dialysis amyloidosis.

Adult↗
PubMedDate not supplied

Bioconjugatable porphyrins bearing a compact swallowtail motif for water solubility.

A broad range of applications requires access to water-soluble, bioconjugatable porphyrins. Branched alkyl groups attached at the branching site to the porphyrin meso position are known to impart high organic solubility. Such "swallowtail" motifs bearing a polar group (hydroxy, dihydroxyphosphoryl, dihydroxyphosphoryloxy) at the terminus of each branch have now been incorporated at a meso site in trans-AB-porphyrins. The incorporation of the swallowtail motif relies on rational synthetic methods whereby a 1,9-bis(N-propylimino)dipyrromethane (bearing a bioconjugatable tether at the 5-position) is condensed with a dipyrromethane (bearing a protected 1,5-dihydroxypent-3-yl unit at the 5-position). The two hydroxy groups in the swallowtail motif of each of the resulting zinc porphyrins can be transformed to the corresponding diphosphate or diphosphonate product. A 4-(carboxymethyloxy)phenyl group provides the bioconjugatable tether. The six such porphyrins reported here are highly water-soluble (> or =20 mM at room temperature in water at pH 7) as determined by visual inspection, UV-vis absorption spectroscopy, or 1H NMR spectroscopy. Covalent attachment was carried out in aqueous solution with the unprotected porphyrin diphosphonate and a monoclonal antibody against the T-cell receptor CD3epsilon. The resulting conjugate performed comparably to a commercially available fluorescein isothiocyanate-labeled antibody with Jurkat cells in flow cytometry and fluorescence microscopy assays. Taken together, this work enables preparation of useful quantities of water-soluble, bioconjugatable porphyrins in a compact architecture for applications in the life sciences.

Flow Cytometry↗
PubMed1995

Mechanism of an ATP-dependent carboxylase, dethiobiotin synthetase, based on crystallographic studies of complexes with substrates and a reaction intermediate.

The crystal structures of six complexes of homodimeric Escherichia coli dethiobiotin synthetase with a variety of substrates, substrate analogs, and products have been determined to high resolution. These include (1) the binary complex of dethiobiotin synthetase and the N7-carbamate of 7,8-diaminononanoic acid, (2) the binary complex of enzyme and the alternate substrate, 3-(1-aminoethyl)-nonanedioic acid, (3) the binary complex of enzyme with the product ADP, (4) the quaternary complex of enzyme, ADP, the N7-carbamate of 7,8-diaminononanoic acid, and Ca2+, (5) the ternary complex of enzyme, the ATP analog adenylyl (beta, gamma-methylene)diphosphonate, and the N7-carbamate of 7,8-diaminononanoic acid, and (6) the quaternary complex of enzyme, the ATP analog adenylyl (beta, gamma-methylene)diphosphonate, 7,8-diaminononanoic acid, and Mn2+. One molecule of each substrate binds to one monomer of the enzyme. ADP and the ATP analogue bind to the classical mononucleotide binding fold with the phosphate groups close to the phosphate binding loop Gly8--Thr16 between beta-strand beta 1 and the N-terminus of alpha-helix alpha 1. The adenine ring is bound in a pocket between beta-strands beta 6 and beta 7. In the quaternary complex with Mn2+, the metal binding site is found in the vicinity of the beta- and gamma-phosphate groups. Two oxygen atoms from the phosphates and oxygen atoms from the side chains of Asp54, Thr16, and Glu115 are ligands to the Mn2+ ion in the quaternary complex. In the complex with ADP and the N7-carbamate of 7,8-diaminononanoic acid prepared in the presence of Ca2+ ions, a different metal binding site is found. The Ca2+ ion is coordinated to an oxygen atom of the alpha-phosphate group of the nucleotide, the side chain of Asp54, and solvent molecules. The 7,8-diaminononanoic acid substrate molecule interacts with residues from both subunits, making the dimer the minimal functional unit. The diamino group binds between the loops after beta 2 and beta 4, and the terminal carboxyl group at the hydrophobic tail of the substrate interacts with the amino terminus of helix alpha 5 and with the side chain of Tyr187 in helix alpha 6 of the second subunit at the monomer-monomer interface. Strong additional electron density close to the N7 nitrogen atom of the 7,8-diaminononanoic acid substrate in some complexes indicates that, even in the absence of added bicarbonate in the crystallization mixture, the carbamylated intermediate is formed in the crystal.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Diphosphate↗
PubMed1996

Structural Variability of the Vanadium-Organodiphosphonate System: Hydrothermal Syntheses and Structural Characterizations of One-Dimensional, Two-Dimensional, and Three-Dimensional Phases.

The hydrothermal chemistry of the CsVO(3)/methylenediphosphonate system was investigated. Variations in reaction temperatures, heating times, and stoichiometries of reactants resulted in the isolation of mononuclear, one-, two-, and three-dimensional species: Cs[VO(HO(3)PCH(2)PO(3)H)(2)(H(2)O)] (1), Cs[VO(HO(3)PCH(2)PO(3))] (2), Cs[(VO)(2)V (O(3)PCH(2)PO(3))(2)(H(2)O)(2)] (3), and [V(HO(3)PCH(2)PO(3))(H(2)O)] (4), respectively. The structure of the anion of 1 consists of isolated V(IV) octahedra. Phase 2 adopts a chain structure constructed from corner-sharing V(IV) octahedra, forming infinite {-V=OV=O-} linkages. The layer structure of 3 contains trinuclear units of corner-sharing {VO(6)} octahedra with the central V site in the III oxidation state and V(IV) centers at the extremities of the cluster. The diphosphonate ligands serve to link neighboring trinuclear motifs into a layer structure three octahedra in depth. The Cs(+) cations occupy cavities within the layers, rather than the more common interlamellar positions. The structure of 4 consists of isolated {V(III)O(6)} octahedra linked by diphosphonate groups into a three-dimensional framework. Crystal data: for 1, CH(6)O(7)P(2)V(0.5)Cs, monoclinic C2, a = 10.991(2) Å, b = 10.161(2) Å, c = 7.445(1) Å, beta = 92.97(3) degrees, Z = 4; for 2, CH(3)O(7)P(2)VCs, monoclinic C2, a = 10.212(2) Å, b = 10.556(2) Å, c = 14.699(3) Å, beta = 94.57(2) degrees, Z = 8; for 3, C(2)H(8)O(16)P(4)V(3)Cs, monoclinic C2/m, a = 9.724(2) Å, b = 8.136(2) Å, c = 10.268(2) Å, beta = 103.75(3) degrees, Z = 2; for 4, CH(5)O(7)P(2)V, monoclinic P2(1)()/n, a = 5.341(1) Å, b = 11.516(2) Å, c = 10.558(2) Å, beta = 99.89(1) degrees, Z = 4.

Journal Article↗
PubMed1975

Properties of inorganic pyrophosphatase of pig scapula cartilage.

The properties of a highly purified inorganic pyrophosphatase (pyrophosphate phosphohydrolase; EC 3.6.1.1) from pig scapula cartilage were studied. The enzyme had a molecular weight of 66 000 and a pH optimum of 7-8. It was markedly activated by magnesium, but not, or only to a much smaller degree, by other metal ions. PP1 was the only substrate found and had a Km value of 11 muM. The enzyme was not inhibited by phosphate and other inhibitors of alkaline phosphatase such as CN- minus, amino acids and theophylline; it was slightly inhibited by tartrate, formaldehyde and ammonium molybdate and strongly inhibited by F- minus, Ca2+ and other metal ions. The properties of the enzyme in the presence of concentrations of PP1 present in plasma (3.5 muM) were similar to those found at higher (2 mM) concentrations of PP1. The diphosphonates ethane-1-hydroxy-1,1-diphosphonate and dichloromethylenediphosphonate inhibited the enzyme in the presence of low PP1 concentrations. The characteristics of this enzyme are therefore similar to pyrophosphatases from other sources, such as from yeast and erythrocytes, and do not support a specific role of this enzyme in the calcification process.

Amino Acids↗
PubMed1975

Changes in the renal and extrarenal handling of phosphate induced by disodium etidronate (EHDP) in man.

1. The diphosphonate, disodium etidronate (disodium ethane-1-hydroxy-1, 1-diphosphonate; (EHDP), is known to increase plasma inorganic phosphate in man. The present study examines the mechanism of this effect. 2. When EHDP was given by mouth at a dose of 80 mumol (20 mg) kg-minus 1day-minus 1, plasma phosphate was significantly increased 24 h after the first dose but did not reach its maximum value for 2-3 weeks. When the drug was stopped, plasma phosphate returned to pretreatment values within 3 weeks. 3. Urinary excretion rate of phosphate was not greatly changed during treatment with EHDP despite the large increase in plasma phosphate, suggesting an alteration in renal handling. This was examined directly by infusing phosphate and inulin in six patients off and on EDPH. 4. EHDP had no effect on glomerular filtration rate (GFR) but produced a large increase in the maximum rate of renal tubular reabsorption of phosphate (TmP). The ratio Tm,P/GFR increased from a mean value of 1.15 mmol/1 to 2.10 mmol/1 on EHDP. This increase accounted for the hyperphosphataemia. 5. The same amount of phosphate infused at the same rate produced a greater rise in plasma phosphate when patients were on EHDP than when they were not, indicating a reduced net rate of entry of phosphate into tissues other than kidney. 6. Fasting total plasma calcium concentration and urine calcium excretion rate were not significantly altered by EHDP but the ability of infused phosphate to decrease plasma calcium was diminished. 7. It is suggested that EHDP alters phosphate transport in kidney and other tissues by a mechanism which is probably independent of the known hormonal influences on phosphate metabolism.

Administration, Oral↗
PubMed1973

Effect of thiostrepton on recycling of Escherichia coli initiation factor 2.

The recycling of initiation factor 2, which requires both GTP and the 50S subunit and involves GTP hydrolysis, appears to be blocked by thiostrepton. However, this antibiotic has little or no effect on the AUG-directed ribosomal binding promoted by initiation factor 2 of fMet-tRNA under conditions that do not permit optimal recycling of the factor. Evidence is presented suggesting that the 50S ribosomal proteins L7 or L12, which are required for the function of the chain elongation factors Tu and G and the accompanying hydrolysis of GTP, are also involved in recycling of initiation factor 2. Although both 5'-guanylylmethylene diphosphonate and thiostrepton seem to block recycling of initiation factor 2, fMet-tRNA bound to the ribosomes in the presence of GTP and thiostrepton can react with puromycin, whereas that bound in the presence of 5'-guanylylmethylene diphosphonate and the antibiotic cannot. It is proposed that initiation factor 2 may interact with two nonidentical ribosomal sites during polypeptide chain initiation.

Anti-Bacterial Agents↗
PubMed1982

Gut-mediated hypercalcemia in rabbits bearing VX2 carcinoma: new mechanism for tumor-induced hypercalcemia.

The VX2 carcinoma-bearing rabbit is an animal model for tumor-induced hypercalcemia, thought to be due to increased bone destruction effected by prostaglandin E2. The present experiments suggest that the pathophysiology of the hypercalcemia differs from that previously proposed. Tumor was transplanted intramuscularly into 2.5- to 3-kg male New Zealand White rabbits, which were conditioned to a 1.5% calcium diet and treated with daily subcutaneous injections of dichloromethane diphosphonate (10 mg . kg-1 . day-1), a potent inhibitor of bone resorption, or 0.9% NaCl (2 ml . kg-1 . day -1). The diphosphonate had no significant effect on plasma Ca2+ in either group. After day 31, half the animals of each group were fed a calcium-free diet. This normalized the plasma Ca2+ in each VX2-bearing rabbit within 3 to 4 days but had little effect in control rabbits. In a second series of experiments, VX2-bearing rabbits maintained on standard rabbit chow were treated for 11 days with parenteral indomethacin (30--60 mg/day) or 0.9% NaCl. Although indomethacin normalized the markedly elevated urinary excretion of prostaglandin E2, both treatment groups became severely hypercalcemic. Dietary calcium restriction promptly restored to normal the plasma Ca2+ concentration. In a third series of experiments, rabbits were fed standard rabbit chow and treated with oral indomethacin (40 mg/day) while control-rabbits were pair fed in identical chow. Transplantation of VX2 tumor into both groups caused hypercalcemia. We conclude that the hypercalcemia produced by this tumor strain is indomethacin resistant and dependent on an increase in gastrointestinal calcium absorption, not on skeletal calcium mobilization.

Animals↗
PubMed1998

Marrow-derived activated macrophages are required during the effector phase of experimental autoimmune uveoretinitis in rats.

PURPOSE: Experimental autoimmune uveoretinitis (EAU), an established model for human endogenous (autoimmune) posterior uveitis, is a CD4+ T cell-mediated disease inducible in Lewis rats by intradermal inoculation with retinal antigens. Immunohistochemical studies have previously documented the lymphocyte profiles during various stages of the disease process. The purpose of the present study was to investigate the role of macrophages in EAU. METHODS: EAU was induced in Lewis rats, and the effect of macrophage depletion, using the drug dichlorodimethylene diphosphonate (Cl2MDP) encapsulated in liposomes and administered intravenously, was assessed based on the clinical and histological profile of the disease. RESULTS: The results have shown that in control animals macrophages occur early, feature prominently throughout the course of the disease and display considerable heterogeneity: marrow-derived ED1+ cells and ED3+ cells are the major infiltrating cells, with many cells also expressing ED7 and ED8. In contrast, few cells expressed the ED2 antigen during EAU, even though ED2+ "resident" macrophages occur in the normal choroid. Macrophage depletion, using intravenously injected dichloromethylene diphosphonate (Cl2MDP) enclosed in liposomes, caused a delay in the onset and a reduction in the severity of EAU when administered during the "effector" stage of the disease, i.e. 9-11 days after inoculation with retinal antigen. The delay in disease onset was greater when liposomes were mannosylated and was accompanied by a reduction in the overall inflammatory cell infiltrate into the eye and reduced tissue damage. In addition, there was a reduction in the level of expression of MHC Class II antigen and CR3 (ED7) antigen, a marker of macrophage activation, in Cl2MDP-treated animals compared to controls. CONCLUSION: These results suggest that blood-borne, activated macrophages are major effectors of tissue damage during EAU.

Animals↗
PubMed1988

Serum osteocalcin concentration in patients with prostatic cancer.

Fifty-four subjects were studied: 36 advanced prostatic adenocarcinoma patients in stage D and 18 normal age-matched male controls. Serum alkaline phosphatase, serum acid phosphatase, plasma osteocalcin, 24-h urinary hydroxyproline excretion, and 24-h whole-body retention of [99mTc]-methylene diphosphonate were measured in all subjects before and 3, 6, and 9 weeks after the start of treatment. Skeletal metastases were identified by radiography and/or [99mTc]-methylene diphosphonate bone scan. The results confirm that acid phosphatase is a significant marker in prostatic cancer; serum alkaline phosphatase may be useful in the evaluation and monitoring of bone metastases but it is not always specific; urinary excretion of hydroxyproline is an index of osteoclastic activity; serum osteocalcin may be considered more specific in the evaluation and monitoring of osteoblastic bone metastases in prostatic cancer.

1-Carboxyglutamic Acid↗
PubMed1978

Bone scan in sickle cell crisis.

99mTc-diphosphonate bone scans of 13 patients in acute sickle crisis were analyzed. Twelve of the 13 patients had abnormal scans, with increased activity in joints and skull being a common finding. One patient with splenic calcification and two patients without splenic calcification had splenic uptake of diphosphonate. Most of the abnormal scans showed hot areas, with cold areas seen only in four cases. There was no correlation between the site of pain clinically and the abnormal areas on scanning. The pathophysiology of the abnormal uptake of radioactivity and the role of bone scanning on sickle cell disease are discussed.

Acute Disease↗