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Positive gallium-67 citrate uptake in a patient with polyostotic fibrous dysplasia.

Fibrous dysplasia is an uncommon bone condition with characteristic radiologic features. It is well known that there is increased uptake of Tc-99m hydroxymethylene diphosphonate (HMDP) and methylene diphosphonate (MDP) in fibrous dysplasia. There are no reports of uptake of Ga-67 citrate by fibrous dysplasia. A case is reported in which positive Ga-67 uptake was seen in a patient with polyostotic fibrous dysplasia.

Fibrous Dysplasia of Bone↗

MR imaging of septic sacroiliitis.

Septic sacroiliitis is difficult to diagnose, causing delayed treatment and increased morbidity. The traditional imaging techniques for diagnosis have been CT and nuclear medicine. Our purpose was to determine the ability of MR imaging to detect septic sacroiliitis, to evaluate the features of septic sacroiliitis with MR, and to compare the relative detection rate of MR, CT, and nuclear medicine. All patients with a discharge diagnosis of septic sacroiliitis who were evaluated by MR imaging of the pelvis were retrospectively evaluated. Five patients were collected with six septic sacroiliac joints, which were also evaluated with CT, 99mTc-methylene diphosphonate bone scans, and 67Ga-citrate scans. Abnormalities consistent with sacroiliitis were seen in all sacroiliac joints both prospectively (impression from the initial report) and retrospectively on MR. In addition to the nonspecific MR findings of inflammation and/or fluid in the sacroiliac joint space, bone marrow of the sacrum and/or ilium, and iliopsoas muscle, fluid/inflammation was uniquely identified tracking posterior to the iliopsoas muscle in each of these patients with septic sacroiliitis. Even in retrospect, a definite diagnosis of sacroiliitis could be made in only five of six joints by 67Ga-citrate scans, three of six joints by CT scans, and one of six joints by 99mTc-methylene diphosphonate bone scans. These results suggest MR imaging may be a sensitive modality in the early diagnosis of septic sacroiliitis.

Adult↗

67Ga uptake at sites of heterotopic calcification: a report of three cases.

Heterotopic calcification occurs commonly in spinal cord injured patients and following joint trauma or surgery. 99Tcm-methylene diphosphonate is useful in the detection of these lesions, many of which are subclinical. Three patients are presented with heterotopic calcification, one with severe hypoxic encephalopathy and two following major trauma. Intense 67Ga uptake within areas of heterotopic calcification was noted in all three patients. Two of the patients also underwent 99Tcm-methylene diphosphonate bone scanning and showed uptake of the bone agent corresponding to the areas of 67Ga uptake. In predisposed patients, heterotopic calcification should be considered in the differential diagnosis of a focal area of 67Ga uptake.

Adult↗

Different patterns of lymphoscintigraphic findings in patients with intestinal lymphangiectasia.

Technetium-99m antimony sulfide colloid lymphoscintigraphy conveniently demonstrates intestinal leakage of lymph in patients with intestinal lymphangiectasia. However, we found no intestinal radioactivity in some patients. We evaluated lymphoscintigraphic findings and compared them with clinical data. Technetium-99m antimony colloid lymphoscintigraphy was performed in 12 patients (age, 8.9+/-6.4 years; male:female=8:4) with histologically proven intestinal lymphangiectasia. After subcutaneous injection of 103.6 MBq of technetium-99m antimony colloid into the webs of both feet, sequential abdominal images were obtained up to 24 h post-injection. Four patients underwent technetium-99m methylene diphosphonate bone scintigraphy. Patients were divided into two groups according to the presence or absence of intestinal radioactivity. Five showed intestinal activity (Group 1), but seven did not (Group 2). No Group 1 patient had a history of ascites, while all Group 2 patients had ascites as the initial manifestation. Serum total protein and albumin levels were significantly lower in Group 1 patients than in Group 2 patients. In three Group 1 patients, technetium-99m methylene diphosphonate bone scintigraphy revealed intestinal radioactivity, while in one Group 2 patient this was not found. We observed two types of lymphoscintigraphic pattern in patients with intestinal lymphangiectasia. To clarify the exact pathophysiology, further study is required.

Adolescent↗

Altered lower limb vascular perfusion in patients with sciatica secondary to disc herniation.

STUDY DESIGN: The present study attempts to document deep vascular abnormalities of the lower extremity in cases of sciatica secondary to discal herniation using Tc-99m methylene diphosphonate angiography. OBJECTIVES: Vascular abnormalities are studied compared with the contralateral extremity and normal control subjects. An attempt is made to determine the clinical usefulness of the current technique. SUMMARY OF BACKGROUND DATA. Thermography has occasionally evidenced a decreased cutaneous temperature in patients with sciatica. There have been no studies to date looking at the total vascular flow in this condition, mainly constituted by the muscular perfusion. METHODS: Thirty patients with sciatica secondary to discal herniation, 16 patients with chronic low back pain referred to the thigh, and 31 control subjects were examined by isotopic angiography of the posterior aspect of the thigh after intravenous injection of Tc-99m methylene diphosphonate. The affected side was compared with the nonpainful side, and the difference was expressed as a percentage. Control subjects were used as reference values. RESULTS: Abnormality in vascularization of the lower extremity was found in 24 (80%) of patients with sciatica and in 11 (68.7%) of the patients with low back pain. The median blood flow difference was, respectively, -12.5% and +4% in these two groups versus +2.9% in the control group. The differences between the sciatica group and the other groups were statistically significant. No correlation was found with the clinical parameters studied. CONCLUSION: Vascular perfusion abnormalities observed in patients with sciatica secondary to disc herniation may be more important than previously considered and possibly result from alteration in sympathetic vascular autoregulation.

Aged↗

Single photon emission computed tomography in otosclerosis: diagnostic accuracy and correlation with age, sex, and sensorineural involvement.

OBJECTIVE: To evaluate the accuracy of single photon emission computed tomography (SPECT) in detecting otospongiotic foci of the labyrinthine capsule in otosclerotic patients and to correlate the metabolic patterns detected by SPECT with age, sex, and sensorineural hearing loss. PATIENTS AND METHODS: Thirty-six patients with surgically confirmed otosclerosis and a control group of 12 subjects with normal hearing; each subject underwent SPECT study of the skull with (99m)technetium-diphosphonate ((99m)Tc-medronate). Statistical analysis of the results was performed by use of the Mann-Whitney U test. RESULTS: SPECT seemed to be very sensitive in differentiating otospongiotic bone from normal bone; in the affected group, only 2 of 72 ears yielded false-negative results (sensitivity 97.2%). Moreover, in the otosclerotic patients, the mean petrosa uptake value was higher than in the control group, a difference that was statistically significant (p < 0.0001). MAIN OUTCOME MEASURES: Regarding uptake in relation to patient age, an inverse relationship was observed between increased metabolic activity and age: the mean uptake index in the younger patients was significantly higher than that in the older patients (p < 0.0001). By contrast, no statistically significant differences were found between men and women (p = 0.1519). Comparison of SPECT alterations with bone conduction thresholds revealed a statistically significant correlation (p = 0.0002 and p = 0.0010) between increased metabolic bone activity and sensorineural involvement only in the younger group of otosclerotic patients. CONCLUSIONS: Diphosphonate bone SPECT is the only functional method that allows in vivo evaluation of disease activity, and it was highly sensitive in detecting otosclerosis. SPECT can be considered useful in the diagnosis of otosclerosis that is difficult to recognize, such as cochlear otosclerosis and far-advanced otosclerosis, and it could also find a place in evaluating the efficacy of medical therapy for otosclerosis.

Adult↗

Bone scan appearance in aggressive osteogenic sarcoma with pleural, lung, bone, and soft-tissue metastases.

A 40-year-old woman presented with a known case of osteogenic sarcoma of the right leg and underwent below-the-knee amputation. The preoperative workup was negative for distant metastases, and the patient was followed regularly. Two years later she developed dyspnea and chest pain. Computed tomography revealed diffuse left lung metastases with pleural involvement and nodular metastases in the right lung. Tc-99m methylene diphosphonate whole-body bone scanning revealed the amputated right leg with a clean stump but with widespread metastases in the right thigh involving soft tissue and bone, and the pelvis, left femur, and skull. In addition, diffuse left lung metastases involving both parietal pleura and lung parenchyma were seen. Tc-99m methylene diphosphonate uptake has been observed in the soft tissue and lungs in patients with osteogenic sarcoma but is rarely observed in practice with this degree of aggressiveness.

Adult↗

Effects of phosphate-modified adenine nucleotide analogues on insulin secretion from perfused rat pancreas.

1 The effects of three methylene analogues of adenosine 5'-triphosphate (ATP) or 5'-diphosphate (ADP) have been studied on insulin secretion from the isolated perfused pancreas of the rat: 5'-adenylmethylene diphosphonate or beta, gamma-methylene ATP, adenosine 5'-alpha, beta-methylene triphosphate or alpha, beta-methylene ATP and adenosine 5'-alpha, beta-methylene diphosphonate or alpha, beta-methylene ADP. 2 beta, gamma-Methylene ATP did not elicit any increase of insulin release: alpha, beta-methylene ATP and alpha, beta-methylene ADP induced a biphasic stimulation of insulin secretion; this effect was dose-related between 1.65 and 165 mumol/l. Relative potency ATP/alpha, beta-methylene ATP was 1.2 and ATP/alpha, beta-methylene ADP was 0.31. 3 Our results point to the importance of the steric and electronic characteristics of the polyphosphate chain of the analogues of ATP and ADP in inducing an insulin secretory effect. They support the hypothesis of a purine receptor for ATP and ADP.

Adenine Nucleotides↗

The cross-linking and structure modification of the collagen matrix in the design of cardiovascular prosthesis.

Glutaraldehyde cross-linking of native or reconstituted collagen fibrils and tissues rich in collagen significantly reduces biodegradation. Other aldehydes are less efficient than glutaraldehyde in generating chemically, biologically, and thermally stable cross-links. Implants of collagenous materials cross-linked with glutaraldehyde are subject long-term to calcification, biodegradation, and low-grade immune reactions. We have attempted to overcome these problems by enhancing cross-linking through (a) bridging of activated carboxyl groups with diamines and (b) using glutaraldehyde to cross-link the epsilon-NH2 groups in collagen and the unreacted amines introduced by aliphatic dismines. This cross-linking reduces tissue degradation and nearly eliminates humoral antibody induction. Covalent binding of diphosphonates, specifically 3-amino-1-hydroxypopane-1, 1-diphosphonic acid (3-APD), and to a lesser extent chondroitin sulfate to collagen or to the cross-ling-enhanced collagen network reduces its potential for calcification. Platelet aggregation also is reduced by glutaraldehyde cross-linking and nearly eliminated by the covalent binding of chondroitin sulfate to collagen. The cytotoxicity of residual glutaraldehyde can be minimized by chemical neutralization and thorough rough rinsing.

Adenosine Diphosphate↗

Rectus abdominis rhabdomyolysis after sit ups: unexpected detection by bone scan.

Uptake of technetium-99m methylene diphosphonate by the rectus abdominis muscle was unexpectedly found in a 29 year old man who had started to perform 30 to 40 sit ups a day for five days before the bone scan. After a week of rest, serum creatine kinase activity was still abnormal but muscle uptake of technetium-99m methylene diphosphonate had ceased. This specific muscle injury after short term sit ups as well as the resolution of the phenomenon within a week are of interest.

Adult↗

Re-186(Sn) HEDP for treatment of multiple metastatic foci in bone: human biodistribution and dosimetric studies.

Investigation of the biodistribution of subtherapeutic amounts of a new, chromatographically purified rhenium-186(tin) hydroxyethylidene diphosphonate radiopharmaceutical have been completed in five patients with metastatic carcinoma to bone. The new agent localizes in metastatic foci in bone in the same manner as do standard technetium-99m diphosphonate bone-scanning agents and appears able to deliver therapeutic radiation doses of thousands of rads (tens of grays) to these metastatic foci while limiting the total red marrow dose to less than 75 rad (0.75 Gy). The simultaneous treatment of multiple metastatic foci in bone appears feasible with this new agent.

Adult↗

Sites and mechanisms of localization of technetium-99m phosphorus radiopharmaceuticals in acute myocardial infarcts and other tissues.

This study was performed to elucidate the localization at the cellular level of technetium-99m phosphorus ((99m)Tc-P) radiopharmaceuticals in acute myocardial infarcts and the mechanisms responsible for (99m)Tc-P uptake in acute myocardial infarcts and other tissues. In 20 dogs with proximal left anterior descending coronary arterial ligation for 1-3 days, elevated calcium levels were measured at all sites of increased (99m)Tc-P uptake (acute myocardial infarcts, necrotic thoracotomy muscle, lactating breast, and normal bone); however, a consistent linear relationship between (99m)Tc-P and calcium levels was not observed. A strong correlation (r = 0.95 and 0.99, n = 2 dogs) was demonstrated between levels of (3)H-diphosphonate and (99m)Tc-P in infarcted myocardium. Autoradiographic studies with (3)H-diphosphonate revealed extensive labeling in the infarct periphery which contained necrotic muscle cells with features of severe calcium overloading, including widespread hypercontraction as well as more selective formation of mitochondrial calcific deposits. Autoradiography also demonstrated labeling of a small population of damaged border zone muscle cells which exhibited prominent accumulation of lipid droplets and focal, early mitochondrial calcification. Cell fractionation studies revealed major localization of both (99m)Tc-P and calcium in the soluble supernate and membrane-debris fractions of infarcted myocardium and less than 2% of total (99m)Tc-P and calcium in the mitochondrial fractions; however, electron microscopic examination showed that mitochondria with calcific deposits were not preserved in the mitochondrial fractions. In vitro studies evaluating the role of serum protein binding on tissue uptake of (99m)Tc-P agents demonstrated that, in spite of significant complexing with serum proteins, serum (99m)Tc-P activity retained the ability to adsorp to calcium hydroxyapatite and amorphous calcium phosphate. In vivo studies showed that concentration of human serum albumin (labeled with iodine-131) in infarcted myocardium reached a maximum of only 3.8 times normal after a circulation time of 96 h, whereas (99m)Tc-P uptake was at least 10 times normal after a circulation time as short as 1 h. It is concluded that: (a) (99m)Tc-P uptake in acutely infarcted myocardium, and possibly other types of soft tissue damage, is limited to necrotic and severely injured cells; (b) concentration of (99m)Tc-P results from selective adsorption of (99m)Tc-P with various forms of tissue calcium stores, including amorphous calcium phosphate, crystalline hydroxyapatite, and calcium complexed with myofibrils and other macromolecules, possibly supplemented by calcium-independent complexing with organic macromolecules; and (c) lack of a linear relationship between (99m)Tc-P and tissue calcium levels mainly results from local differences in composition and physicochemical properties of tissue calcium stores and from local variations in levels of blood flow for delivery of (99m)Tc-P agents.

Animals↗

Systemic radionuclide therapy in pain palliation.

Several radiopharmaceuticals were investigated to determine their efficacy and toxicity in the palliation of painful bone metastases. Data on the influence of rhenium-188 hydroxyethylidene diphosphonate (188Re-HEDP), rhenium-186 hydroxyethylidene diphosphonate (186Re-HEDP), and strontium-89 (89Sr) on pain symptoms, quality of life, and bone-marrow function were obtained in 64 patients with breast and prostate cancer. Thirty-one patients were treated with 188Re-HEDP (3194 +/- 387 MBq), 15 patients with 186Re-HEDP (1358 +/- 158 MBq), and 18 patients with 89Sr (152 +/- 19 MBq). The 188Re-HEDP group included six breast cancer patients and 25 prostate cancer patients; the 186Re-HEDP group included three breast cancer patients and 12 prostate cancer patients; and the 89Sr group included three breast cancer patients and 15 prostate cancer patients. All subjects participated in an interview using a standardized sets of questions before and after the 12-week term of therapy. Blood counts were taken weekly for six weeks and after 12 weeks. Results showed that 77 percent of patients reported pain relief after treatment with 188Re-HEDP, 67 percent after treatment with 186Re-HEDP, and 72 percent after treatment with 89Sr. Sixteen percent of patients treated with 188Re-HEDP, 13 percent treated with 186Re-HEDP, and 17 percent treated with 89Sr were able to discontinue their analgesics and were pain-free. Patients described an improvement on Karnofsky performance status (KPS) from 73 +/- 7 percent to 85 +/- 8 percent 12 weeks after 188Re-HEDP (p < 0. 05), from 72 +/- 13 percent to 79 +/- 12 percent after 186Re-HEDP (p = 0.251), and from 62 +/- 14 percent to 69 +/- 16 percent after 89Sr (p = 0.415). Only three patients undergoing 188Re-HEDP therapy, one undergoing 186Re-HEDP therapy, and three undergoing 89Sr therapy had thrombocytopenia (platelet count below 100 x 10(3)/microl) following treatment. The maximum nadir of platelet and leukocyte counts was observed between the second and fifth week after treatment for all radionuclides and was reversible within 12 weeks. The nadir was earlier for 188Re-HEDP with a shorter physical half-life compared with 89Sr. There were no significant differences in bone marrow toxicity (p = 0.123-0.421). Results of this study indicate that all evaluated radiopharmaceuticals were effective in pain palliation without induction of severe side effects. The increase in KPS after 188Re-HEDP was the only statistically significant finding (p = 0.001).

Aged↗

Technetium-99m ciprofloxacin imaging in the diagnosis of postsurgical bony infection and evaluation of the response to antibiotic therapy: A case report.

The use of radiolabelled antibiotics is fast emerging as a promising diagnostic test for the detection of infective lesions, because of their specific binding to the bacterial component. Ciprofloxacin is a broad-spectrum antibiotic that has been used as a radiolabelled antibiotic in both the diagnosis of infections in rabbits and in clinical trials on humans. The diagnosis of skeletal microbial infections remains a challenge, especially in orthopaedic patients with implants. We present a case report of a patient with undiagnosed and unrelenting pain in the lower third of the left leg, which had persisted for 6 months. A novel scintigraphy, which was developed in-house using a 99mTC ciprofloxacin single vial kit, was used for diagnosing the active bacterial infection. A 99mTC methylene diphosphonate bone scan was also performed to locate precisely the site of the lesion. Gradually increasing concentrations of both the radiotracers confirmed the presence of active bacterial infection in the distal third of the left tibia. Follow-up scanning after antibiotic therapy showed the disappearance of the pooling of 99mTC ciprofloxacin, indicating a good response. Therefore, 99mTC ciprofloxacin has good diagnostic and prognostic applications in deep-seated covert skeletal microbial infections. However, the persistence of a focal concentration detected by the 99mTC methylene diphosphonate scan was attributed to the inflammatory and not the infective pathology.

Adult↗

Potential inhibitors of rat tooth alkaline phosphatase studied by means of different histochemical techniques.

Two histochemical methods for demonstration of alkaline phosphatase activity, a lead pyrophosphate- anda naphtholphosphate technique, were compared. Since different results may be due to methodological differences as well as different enzyme activities, the enzymatic hydrolysis of the naphtholphosphate was visualized both by means of an azo-dye coupler and by lead-capturing of the liberated phosphate ion. Various potential inhibitors of alkaline phosphatase activity (diphosphonate, D-penicillamine, and sodium fluoride) were also tested. The use of diphosphonate and D-penicillamine resulted in inhibited or reduced staining, which could mainly be explained by an interference by these compounds with components in the incubation media rather than with the enzyme itself. The addition of sodium fluoride had no effect on the naphtholphosphate staining pattern irrespective of capturing method, whereas the odontoblastic pyrophosphate splitting alkaline phosphatase appeared to be sensitive to sodium fluoride, suggesting the presence of two alkaline phosphatases in odontoblasts.

Alkaline Phosphatase↗

Review article-Bone scanning.

The discovery of a number of phosphate complexes labelled with 99-Tc-m that localize in bone has aroused wide-spread interest in bone scanning. The physiological properties of these and other clinically useful bone-seeking radiopharmaceuticals are compared, and their physical properties assessed in relation to the characteristics and limitations of avilable detector systems. A hypothesis is put forward to explain the behaviour of the technetium-labelled agents. It is concluded that although there are differences in biochemical behaviour between these agents, strontium and fluorine, all three may, under suitable conditions, give similar clinical information. The radiation dose received by the patients is least with the usual dose of 99-Tc-m and the blood clearance of the diphosphonate and pyrophosphate preparations is faster than that of strontium, although slower than fluorine. The psi-ray energy of technetium permits a much greater efficiency of detection than of fluorine. These factors, toghether with the general availability of 99-Tc-m and its relatively low cost make the technetium diphosphonate or pyrophosphate preparations the agents of choice for most skeletal radioisotope imaging. However, there are as yet insufficient follow-up studies to be able to assess the incidence of either false-negative or false-positive findings with these agents.

Adolescent↗

Myositis ossificans progressiva. Clinical features of eight patients and their response to treatment.

The clinical features of eight patients with myositis ossificans progressiva are described and the effects of treatment with the diphosphonate EHDP, together with surgical removal of ectopic bone, are assessed. Early correct diagnosis remains unusual, mainly because the significance of the short great toes is unrecognised, and because myositis may be mistaken for bruising, sarcoma or mumps. The diphosphonate disodium etidronate (EDHP) was given to all patients in an attempt to suppress calcification of new lesions; in five of them ectopic bone was removed during the treatment. EHDP sometimes delayed the mineralisation of newly formed bone matrix after surgical removal but this delay could not be predicted. The variable effect of EHDP may depend particularly on the amount absorbed and on the activity of new bone formation.

Adolescent↗

Ribbing disease (multiple diaphyseal sclerosis): imaging and differential diagnosis.

OBJECTIVE: This study describes the clinical presentation and the course of Ribbing disease in six patients and illustrates imaging features on plain radiography, conventional and computed tomography, and 99mTc-methylene diphosphonate bone scans. MATERIALS AND METHODS: Between 1982 and 1990, six female patients presented with painful bony lesions that were believed to be Ribbing disease. Ten bones were affected: both tibiae in three patients, a unilateral tibia in one, both femora in one, and a unilateral femur in one. Plain radiographs and either conventional or computed tomography were available for all patients and 99mTc-methylene diphosphonate bone scans, for five patients. All patients underwent open biopsy and/or surgical decompression. RESULTS: The diagnosis was reached in all patients through a combination of clinical findings (lack of systemic signs of infection or laboratory values suggesting metabolic bone disease), imaging, histologic evaluation, and specimen cultures. Radiographs and tomographic studies showed benign-appearing endosteal and periosteal cortical thickening. Intense uptake of radionuclide tracer was confined to the shaft of all involved bones. All pathologic specimens revealed nonspecific changes that included a slow increase in the mass of cortical and endosteal bone. These specimens also assisted in excluding neoplastic or infectious causes for the new bone formation. CONCLUSION: Ribbing disease is a rare disorder that, on imaging studies, may simulate stress fracture, chronic infection, bone-forming neoplasia, or a systemic metabolic or endocrine disorder. Clinical and imaging features may suggest the correct diagnosis.

Adult↗