Subcutaneous versus intravenous insulin therapy for glucose control in non-diabetic trauma patients. A randomized controlled trial.

WHAT IS KNOWN AND OBJECTIVE: Hyperglycaemia in trauma patients admitted to the intensive care unit (ICU) is associated with increased morbidity and mortality. Our pilot study is a prospective randomized controlled trial comparing the impact of two glucose control regimens on outcomes in non-diabetic trauma patients admitted with hyperglycaemia to the ICU. METHODS: Trauma patients with blood glucose levels (BGLs) ≥7·8 mm within the first 48 h of the hospital admission were randomized to receive intermittent SQ or continuous IV insulin to maintain BGLs between 4·4 and 6·1 mm. We excluded diabetics on the basis of history, or a glycosylated haemoglobin ≥6% on admission. We compared the effect of SQ vs. IV insulin therapy on the ICU length of stay (ILOS). RESULTS AND DISCUSSION: A total of 58 patients were included in the study. The SQ and IV groups were comparable in terms of age, gender, injury severity, revised trauma, Glasgow coma scores and type of trauma (blunt vs. penetrating). There was no significant difference between the two treatment groups in the ILOS (3 vs. 2 days, P = 0·084), hospital length of stay (8 vs. 6, P = 0·09), ventilator support days (6 vs. 3, P = 0·98), requirement for blood transfusion (P = 0·66), rates of infections (P = 0·70), acute kidney injury (P = 0·99) and mortality (P = 0·61). WHAT IS NEW AND CONCLUSION: There was no difference between SQ and IV insulin therapy in the ILOS in non-diabetic trauma patients.

Risks associated with magnetic resonance imaging and cervical collar in comatose, blunt trauma patients with negative comprehensive cervical spine computed tomography and no apparent spinal deficit.

INTRODUCTION: In blunt trauma, comatose patients (Glasgow Coma Scale score 3 to 8) with a negative comprehensive cervical spine (CS) computed tomography assessment and no apparent spinal deficit, CS clearance strategies (magnetic resonance imaging [MRI] and prolonged cervical collar use) are controversial. METHODS: We conducted a literature review to delineate risks for coma, CS instability, prolonged cervical collar use, and CS MRI. RESULTS: Based on our search of the literature, the numbers of functional survivor patients among those who had sustained blunt trauma were as follows: 350 per 1,000 comatose unstable patients (increased intracranial pressure [ICP], hypotension, hypoxia, or early ventilator-associated pneumonia); 150 per 1,000 comatose high-risk patients (age > 45 years or Glasgow Coma Scale score 3 to 5); and 600 per 1,000 comatose stable patients (not unstable or high risk). Risk probabilities for adverse events among unstable, high-risk, and stable patients were as follows: 2.5% for CS instability; 26.2% for increased intensive care unit complications with prolonged cervical collar use; 9.3% to 14.6% for secondary brain injury with MRI transportation; and 20.6% for aspiration during MRI scanning (supine position). Additional risk probabilities for adverse events among unstable patients were as follows: 35.8% for increased ICP with cervical collar; and 72.1% for increased ICP during MRI scan (supine position). CONCLUSION: Blunt trauma coma functional survivor (independent living) rates are alarming. When a comprehensive CS computed tomography evaluation is negative and there is no apparent spinal deficit, CS instability is unlikely (2.5%). Secondary brain injury from the cervical collar or MRI is more probable than CS instability and jeopardizes cerebral recovery. Brain injury severity, probability of CS instability, cervical collar risk, and MRI risk assessments are essential when deciding whether CS MRI is appropriate and for determining the timing of cervical collar removal.

Prolonged morphine treatment targets delta opioid receptors to neuronal plasma membranes and enhances delta-mediated antinociception.

Opioid receptors are known to undergo complex regulatory changes in response to ligand exposure. In the present study, we examined the effect of morphine on the in vitro and in vivo density and trafficking of delta opioid receptors (deltaORs). Prolonged exposure (48 hr) of cortical neurons in culture to morphine (10 microm) resulted in a robust increase in the internalization of Fluo-deltorphin, a highly selective fluorescent deltaOR agonist. This effect was mu-mediated because it was entirely blocked by the selective mu opioid receptor antagonist d-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr-NH(2) and was reproduced using the selective mu agonist fentanyl citrate. Immunogold electron microscopy revealed a marked increase in the cell surface density of deltaORs in neurons exposed to morphine, indicating that the increase in Fluo-deltorphin internalization was caused by increased receptor availability. Prolonged morphine exposure had no effect on deltaOR protein levels, as assessed by immunocytochemistry and Western blotting, suggesting that the increase in bioavailable deltaORs was caused by recruitment of reserve receptors from intracellular stores and not from receptor neosynthesis. Complementary in vivo studies demonstrated that chronic treatment of adult rats with morphine (5-15 mg/kg, s.c., every 12 hr) similarly augmented targeting of deltaORs to neuronal plasma membranes in the dorsal horn of the spinal cord. Furthermore, this treatment markedly potentiated intrathecal d-[Ala(2)]deltorphin II-induced antinociception. Taken together, these results demonstrate that prolonged stimulation of neurons with morphine markedly increases recruitment of intracellular deltaORs to the cell surface, both in vitro and in vivo. We propose that this type of receptor subtype cross-mobilization may widen the transduction repertoire of G-protein-coupled receptors and offer new therapeutic strategies.

Palliation of pain associated with metastatic bone cancer using samarium-153 lexidronam: a double-blind placebo-controlled clinical trial.

PURPOSE: To evaluate the effectiveness and safety of samarium-153 (153Sm) lexidronam (EDTMP) in a double-blind, placebo-controlled study. PATIENTS AND METHODS: Patients with painful bone metastases secondary to a variety of primary malignancies were randomized to receive 153Sm-EDTMP 0.5 or 1.0 mCi/kg, or placebo. Treatment was unblinded for patients who did not respond by week 4, with those who had received placebo eligible to receive 1.0 mCi/kg of active drug in an open-label manner. Patient and physician evaluations were used to assess pain relief, as was concurrent change in opioid analgesia. RESULTS: One hundred eighteen patients were enrolled onto the study. Patients who received 1.0 mCi/kg of active drug had significant reductions in pain during each of the first 4 weeks in both patient-rated and physician-rated evaluations. Pain relief was observed in 62% to 72% of those who received the 1.O-mCi/kg dose during the first 4 weeks, with marked or complete relief noted in 31% by week 4. Persistence of pain relief was seen through week 16 in 43% of patients who received 1.0 mCi/kg, of active drug. A significant correlation (P = .01) was observed between reductions in opioid analgesic use and pain scores only for those patients who received 1.0 mCi/kg 153Sm-EDTMP. Bone marrow suppression was mild, reversible, and not associated with grade 4 toxicity. CONCLUSION: A single dose of 1.0 mCi/kg of 153Sm-EDTMP provided relief from pain associated with bone metastases. Pain relief was observed within 1 week of administration and persisted until at least week 16 in the majority of patients who responded.

Dobutamine-atropine stress echocardiography and dipyridamole sestamibi scintigraphy for the detection of coronary artery disease: limitations and concordance.

OBJECTIVES: We sought to compare dobutamine-atropine stress echocardiography (DASE) and dipyridamole Technetium 99-m (Tc-99m) sestamibi single photon emission computed tomography (SPECT) scintigraphy (DMIBI) for detecting coronary artery disease (CAD). BACKGROUND: Both DASE and DMIBI are effective for evaluating patients for CAD, but their concordance and limitations have not been directly compared. METHODS: To investigate these aims, patients underwent multistage DASE, DMIBI and coronary angiography within three months. Dobutamine-atropine stress echocardiography and stress-rest DMIBI were performed according to standard techniques and analyzed for their accuracy in predicting the extent of CAD. Segments were assigned to vascular territories according to standard models. Angiography was performed using the Judkin's technique. RESULTS: The 183 patients (mean age: 60 +/- 11 years, including 50 women) consisted of 64 patients with no coronary disease and 61 with single-, 40 with two- and 18 with three-vessel coronary disease. Dobutamine-atropine stress echocardiography and DMIBI were similarly sensitive (87%, 104/119 and 80%, 95/119, respectively) for the detection of CAD, but DASE was more specific (91%, 58/64 vs. 73%, 47/64, p < 0.01). Sensitivity was similar for the detection of CAD in patients with single-vessel disease (84%, 51/61 vs. 74%, 45/61, respectively) and multivessel disease (91%, 53/58 vs. 86%, 50/58, respectively). Multiple wall motion abnormalities and perfusion defects were similarly sensitive for multivessel disease (72%, 42/58 vs. 66%, 38/53, respectively), but, again, DASE was more specific than DMIBI (95%, 119/125 vs. 76%, 95/125, respectively, p < 0.01). Dobutamine-atropine stress echocardiography and DMIBI were moderately concordant for the detection and extent of CAD (Kappa 0.47, p < 0.0001) but were only fairly (Kappa 0.35, p < 0.001) concordant for the type of abnormalities (normal, fixed, ischemia or mixed). CONCLUSIONS: Dobutamine-atropine stress echocardiography and DMIBI were comparable tests for the detection of CAD. Both were very sensitive for the detection of CAD and moderately sensitive for the extent of disease. The only advantage of DASE was greater specificity, especially for multivessel disease. Dobutamine-atropine stress echocardiography may be advantageous in patients with lower probabilities of CAD.

Long-term intravenous antibiotic therapy in chronic osteomyelitis.

Because the optimal treatment of chronic osteomyelitis is not well established, we studied the efficacy of prolonged (three months or more) outpatient intravenous antibiotic therapy via a Hickman catheter. Seventeen patients were entered into our protocol (13 with chronic osteomyelitis, three with chronic septic arthritis, and one with subacute osteomyelitis). Pseudomonas aeruginosa was the most common bone isolate, followed by Staphylococcus aureus. Most patients had polymicrobial isolates. Patients were followed up with clinical examinations, serial measurements of erythrocyte sedimentation rate, and scans using technetium Tc 99m medronate and gallium citrate Ga 67. Of the ten patients with chronic osteomyelitis who completed therapy, eight were considered cured. After further follow-up, three of the cured patients had recurrences requiring additional therapy.

Hemopoiesis in cellulose ester membrane: characterization of the epilayer responsible for recognition and lodgement of hemopoietic cells.

Following intraperitoneal (i.p.) insertion of cellulose ester membranes in the mouse, the membranes develop a cellular coat that after sublethal irradiation and i.p. infusion of marrow cells supports the growth of hemopoietic colonies. The uppermost layer of this cellular coat (the epilayer) becomes extremely attenuated and develops numerous microvilli that interact with infused cells to trap and lodge them. This phenomenon is analogous to specific lodging of hemopoietic stem cells in the marrow after bone marrow transplantation. The mechanism of this interaction is not clear, but attention has recently focused on specific interaction of sugar residues of membrane glycoproteins. We have characterized the free surface of this epilayer with various lectins, glycosylated ferritins, and antifactor VIII antibody. There is strong binding of the three lectins Ricinis communis agglutinin (RCA II), phytohemagglutinin (PHA), and wheat germ agglutinin (WGA), but not Ulex europeaus agglutinin, concanavalin A, the tested glycosylated ferritins, or antifactor VIII antibody. The highest density of binding is on microvilli. Since marrow sinus endothelium also strongly binds RCA II, PHA, and WGA, it is possible that the sugar residues of membrane glycoproteins specifically binding these lectins are responsible for cellular and molecular recognition and transport across the epilayer.

Comparison of single-photon emission computed tomography with [123I]iodoamphetamine and xenon-enhanced computed tomography for assessing regional cerebral blood flow.

Regional CBF (rCBF) images obtained from xenon-enhanced computed tomography (XeCT) and single-photon emission computed tomography (SPECT) with N-isopropyl-p-[123I]iodoamphetamine (IMP) done with a rotating gamma-camera were compared in nine patients. Both XeCT and SPECT/IMP demonstrated flow abnormalities at all sites of infarction identified by CT, while detecting reduced rCBF in areas normal by CT in eight of the nine patients. All areas that were abnormal on XeCT were abnormal on the comparable SPECT/IMP images. The major advantages of XeCT are its greater resolution and potential for noninvasive quantitation of rCBF, while the major advantage of SPECT/IMP is its visualization of the entire brain on transverse, coronal, and sagittal sections.

Nutritional factors in diabetics with and without retinopathy.

We used 3-d food-record-keeping techniques to examine nutritional factors in diabetic patients with and without retinopathy. Patients without retinopathy had significantly higher daily intakes of total carbohydrate, water-soluble dietary fibers, insoluble dietary fibers, and glucose than did patients with retinopathy. Also, patients without retinopathy took a significantly lower proportion of their total daily calories as protein.

Alzheimer disease: lack of effect of lecithin treatment for 3 months.

Eleven outpatients with Alzheimer disease of moderate severity completed a double-blind placebo-controlled crossover trial of lecithin. Each patient received 10 gm three times daily of a placebo for 3 months. Plasma choline levels rose threefold and remained at that level throughout the lecithin administration period. A significant difference between mean baseline scores and treatment scores was found on tests of new learning ability, indicating a practice effect in these tests. However, there were no differences between mean placebo and lecithin scores on any of the psychological test measures.

Regulation of endogenous acetylcholine release from mammalian brain slices by opiate receptors: hippocampus, striatum and cerebral cortex of guinea-pig and rat.

The effects of opiate agonists on acetylcholine release from hippocampal, striatal and cerebral cortical slices were tested; tissue from rat was compared to that from guinea-pig. The results show that opiate receptors in each of these areas can alter the evoked release of acetylcholine from nerve terminals; however, there are species and tissue differences with respect to the apparent subtype of opiate receptor effective. In the hippocampus and striatum of the two species studied, opiates caused a dose-dependent decrease in evoked acetylcholine release from tissue slices but in the guinea-pig kappa-selective agonists were effective, and mu or delta agonists were not, whereas in the rat, mu-, but not delta- or kappa-selective drugs were effective. Opiates also altered acetylcholine release from the frontal, parietal and occipital cortex of both of these species. In all three regions of the guinea-pig cortex, kappa and delta agonists were active and in the parietal cortex mu agonists were also active; rat cortical slices showed similar results except that delta agonists were not effective. The inhibitory effects of the opiate agonists were effectively antagonized by the non-selective opiate antagonist naloxone and by the calcium channel agonists, BAY K 8644 or YC-170. In addition, the effects of the opiate drugs tested in this study on acetylcholine release were confined to evoked release, that is, spontaneous acetylcholine release was not affected. The results suggest that in guinea-pig and rat brain, opiate receptors regulate acetylcholine release, and that, although the subtypes of opiate receptors involved in this effect are different in the two species and in different tissues from the same species, the effect results from a common mechanism that involves alterations of calcium influx into the nerve terminals during depolarization.

Hemicholinium impairs septo-hippocampal facilitatory action.

Intraventricular injections of hemicholinium-3 led to a sharp reduction in hippocampal acetylcholine content (by 79% on the average). This was associated with the following changes in population spikes evoked in area CA1 by commissural stimulation: (1) a tendency to progressive increase, over 1-2 hours; (2) in a few cases (3 out of 12), a striking depression of the normal strong facilitation produced by brief tetanic stimulation of the medial septum (typically 10 pulses at 50-100 Hz); (3) a much more consistent tendency towards fading of the septal facilitatory effect during repeated applications of such brief septal tetani (in 10 cases out of 12); as well as, (4) diminished facilitation by sustained, lower frequency septal tetanic stimulation (20-50 Hz). The reduced efficiency of septal action--especially during repetitive stimulation--was not accompanied by a consistent reduction of the facilitation produced by local applications of acetylcholine; it is, therefore, best explained by the diminished availability of acetylcholine, and so provides further evidence that septo-hippocampal facilitation is mediated by a cholinergic mechanism.

Dynamics of large dense-cored vesicles in synaptic boutons of the cat superior cervical ganglion.

We have shown previously that stimulation of the cat cervical sympathetic trunk for 2 h at 40 Hz depletes the large dense-cored vesicle store in synaptic boutons of the superior cervical ganglion and that post-depletion recovery of the store takes several days. In the present study, we examine the properties of the depletion and recovery mechanisms. Invaginations of the plasmalemma suggestive of the exocytosis of dense cores were seen frequently in boutons from stimulated ganglia. The depletion process is calcium dependent: in ganglia perfused with calcium-free Krebs solution no depletion was produced by 40 Hz preganglionic stimulation. The depletion process is rapid: during continuous stimulation of the cervical sympathetic trunk with 40 Hz, depletion observed by the end of 2 h was similar to depletion by the end of the initial 5 min of stimulation. The depletion process is frequently dependent: when the cervical sympathetic trunk was stimulated with a constant number of stimuli, no depletion occurred at the frequency of 2 or 10 Hz, while the frequencies of 20 and 40 Hz produced depletion, which was greater at 40 Hz. Recovery of the large dense-cored vesicle store during the initial 24 h after 10 min of 40 Hz stimulation was faster, and of approximately the same magnitude, than during the succeeding five days. Recovery of the store after stimulus-evoked depletion was prevented by application of colchicine to the cervical sympathetic trunk, which suggests dependence of recovery on fast axonal transport. Large dense-cored vesicles accumulated in the colchicine-treated segment of cervical sympathetic trunk axons. In conclusion, these observations suggest that the stimulus-evoked depletion of large dense-cored vesicle stores in synaptic boutons of the cat superior cervical ganglion is the result of calcium-dependent exocytosis of the large dense-cored vesicle core and that the post-stimulus recovery is critically dependent on microtubule-mediated axonal transport.

Epidermal growth factor affects both glia and cholinergic neurons in septal cell cultures.

The effects of epidermal growth factor on high density primary cultures of fetal (embryonic day 17) rat septal cells were examined. Under serum-free conditions, the continuous exposure of these cultures to epidermal growth factor for seven days significantly decreased choline acetyltransferase (EC 2.3.1.6) activity in a dose-dependent manner. Maximal decreases were observed from 1 to 10 ng/ml epidermal growth factor. This effect was completely abolished by the addition of anti-epidermal growth factor antibodies. The epidermal growth factor-mediated decrease in choline acetyltransferase activity was culture-time dependent, being first detectable after five days of factor application and may likely represent an inhibition of the spontaneous increase in enzyme activity that occurs with time in culture. Concomitant with changes in enzyme activity, epidermal growth factor produced a significant and proportional decrease in the number of acetylcholinesterase-positive neurons. This decrease in acetylcholinesterase-positive cells did not reflect a decrease in cholinergic cell survival as nerve growth factor could restore the number of acetylcholinesterase-positive neurons in epidermal growth factor-treated cultures to control levels. Furthermore, in these high-density cultures, epidermal growth factor did not affect general neuronal survival, while it did produce an increase in the number and intensity of glial fibrillary acidic protein-immunoreactive astroglia as well as in the number of macrophage-like cells. The proliferative response of these non-neuronal cells to epidermal growth factor, as assessed by [3H]thymidine incorporation, was evident after three days of epidermal growth factor application, persisted thereafter, and could be antagonized by the inclusion of the antimitotic 5-fluorodeoxyuridine. Furthermore, 5-fluorodeoxyuridine completely blocked the epidermal growth factor-mediated decrease in choline acetyltransferase activity. However, when epidermal growth factor was tested in pure glial cultures, it only directly induced proliferation of astrocytes. These results suggest that the proliferative response of either one or both of these glial cell types in the mixed cultures may be indirectly affecting cholinergic cell expression.

The release of acetylcholine and of catecholamine from the cat's adrenal gland.

The cat's adrenal gland was perfused in situ with Krebs solution containing eserine; the amount of acetylcholine and of catecholamine released was measured. Splanchnic nerve stimulation (5 Hz for 2 min) increased the release of acetylcholine and catecholamine; the molar ratio of evoked release of catecholamine to acetylcholine was 122 +/- 8. It is suggested that this amplification is achieved because a chromaffin cell granule contains more mediator than does the acetylcholine quantum that releases it. The release per impulse of catecholamine during splanchnic nerve stimulation at 30 Hz was less than that released by stimulation at 1 or 5 Hz. This depression is attributed to a presynaptic failure, because the release of acetylcholine was similarly frequency dependent. The release of catecholamine was linearly related to the release of acetylcholine over the range tested, indicating that the input-output relationship at the splanchnic-adrenal medullary junction is linear. During continuous stimulation of the splanchnic nerve (5 Hz), catecholamine release declined to a level that was 32 +/- 2% of the initial output. This fatigue is attributed primarily to a postsynaptic depression, because the release of acetylcholine was maintained at 71 +/- 6% of its initial level. The presence of eserine in the perfusate was necessary for the release of acetylcholine to be detected, but in the presence of eserine catecholamine release was 90 +/- 10% that in the drug's absence. It is concluded that released acetylcholine is hydrolysed at some distance from its site of release and action. Glands perfused with raised K+ released acetylcholine and catecholamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin-like growth factor-I inhibits endogenous acetylcholine release from the rat hippocampal formation: possible involvement of GABA in mediating the effects.

Evidence suggests that insulin-like growth factor-I (IGF-I) plays an important role during brain development and in the maintenance of normal as well as activity-dependent functioning of the adult brain. Apart from its trophic effects, IGF-I has also been implicated in the regulation of brain neurotransmitter release thus indicating a neuromodulatory role for this growth factor in the central nervous system. Using in vitro slice preparations, we have earlier reported that IGF-I potently inhibits K(+)-evoked endogenous acetylcholine (ACh) release from the adult rat hippocampus and cortex but not from the striatum. The effects of IGF-I on hippocampal ACh release was sensitive to the Na(+) channel blocker tetrodotoxin, suggesting that IGF-I might act indirectly via the release of other transmitters/modulators. In the present study, we have characterized the possible involvement of GABA in IGF-I-mediated inhibition of ACh release and measured the effects of this growth factor on choline acetyltransferase (ChAT) activity and high-affinity choline uptake in the hippocampus of the adult rat brain. Prototypical agonists of GABA(A) and GABA(B) receptors (i.e. 10 microM muscimol and 10 microM baclofen) inhibited, whereas the antagonists of the respective receptors (i.e. 10 microM bicuculline and 10 microM phaclofen) potentiated K(+)-evoked ACh release from rat hippocampal slices. IGF-I (10 nM) inhibited K(+)- as well as veratridine-evoked ACh release from rat hippocampal slices and the effect is possibly mediated via the activation of a typical IGF-I receptor and the subsequent phosphorylation of the insulin receptor substrate-1 (IRS-1). The inhibitory effects of IGF-I on hippocampal ACh release were not additive to those of either muscimol or baclofen, but were attenuated by GABA antagonists, bicuculline and phaclofen. Additionally, in contrast to ACh release, IGF-I did not alter either the activity of the enzyme ChAT or the uptake of choline in the hippocampus. These results, taken together, indicate that IGF-I, under acute conditions, can decrease hippocampal ACh release by acting on the typical IGF-I/IRS receptor complex while having no direct effect on ChAT activity or the uptake of choline. Furthermore, the evidence that effects of IGF-I could be modulated, at least in part, by GABA antagonists suggest that the release of GABA and the activation of its receptors may possibly be involved in mediating the inhibitory effects of IGF-I on hippocampal ACh release.

Probe amplifier system based on chimeric cycling oligonucleotides.

Amplification systems are required as part of DNA probe technology, since traditional non-amplified oligonucleotide hybridization using nonradioactive detection methods have detection limits of approximately 10(8) molecules. We present a probe amplifier technology suitable for use in large-scale automated clinical diagnostic systems. It is fast, sensitive and performs at a constant temperature. The system functions by allowing a single target molecule to act as a catalyst in converting a large number of probe molecules to a unique detectable form. We refer to this catalytic amplification process as the "cycling probe reaction." The basis of the system is an oligomer probe construction consisting of a DNA-RNA-DNA sequence.

Current imaging strategies for colorectal cancer.

Endoscopy and barium enema examinations are used to identify the primary site of disease in patients with clinical suspicion of colorectal cancer. Once colorectal cancer has been confirmed by imaging studies and biopsy, preoperative evaluation is directed toward accurate disease staging. Most currently available imaging techniques are inaccurate for detecting transmural extension, perienteric spread of tumors and distant lymph node involvement. Although both computed tomography (CT) and magnetic resonance imaging (MRI) have an unacceptably low sensitivity for accurate staging, CT is clearly superior to MRI for detecting extrahepatic metastases. Transrectal ultrasonography, however, is a promising new method for detecting perirectal spread of disease. The diagnostic efficacy of MRI and intravenous dynamic hepatic CT for detecting liver metastases is approximately equal. CT during arterial portography is recommended before resection of solitary liver metastases. Chest radiography is also part of the routine preoperative evaluation. Bone scans are rarely performed in patients without the skeletal pain suggestive of bone metastases. During the years following surgery for colorectal cancer, many patients undergo special imaging studies to identify local tumor recurrence, secondary tumor growth elsewhere within the large bowel and both regional and distant spread of disease. Thus, for the patient with a sharply increasing carcinoembryonic antigen level, CT of the abdomen and liver is the current recommendation. Immunoscintigraphy is a new imaging modality that addresses some of the limitations of current diagnostic procedures for colorectal cancer. This procedure gives whole body information on disease extent, especially in the extrahepatic abdomen and pelvis, and can therefore contribute to patient management decisions.

Bone scintigraphy: Part 2. Orthopedic bone scanning.

Bone scanning provides a functional assessment of skeletal pathology not available with conventional radiography or special radiographic techniques such as CT and MRI. Bone scanning detects osteoblastic activity associated with many forms of orthopedic skeletal disease. Several of the more common orthopedic applications of bone scanning have been described above, while equally important topics such as prothesis loosening, avascular necrosis, and the reflex sympathetic dystrophy syndrome were not considered. Thus, for a great range of benign skeletal pathology, bone scanning can provide the orthopedic surgeon with practical information concerning the cause of the patient's pain, the true significance of otherwise questionable radiographic findings, the extent of disease and the results of orthopedic surgical treatment.

Heterotopic ossification.

Heterotopic ossification (HO) is the presence of bone in soft tissue where bone normally does not exist. The acquired form of HO most frequently is seen with either musculoskeletal trauma, spinal cord injury, or central nervous system injury. For example, patients who have recently undergone total hip arthroplasty or have paraplegia after spinal cord injury are at risk for HO. The fever, swelling, erythema, and occasional joint tenderness seen in early HO can be difficult to distinguish from cellulitis, osteomyelitis, or thrombophlebitis. Bone scanning and other imaging tests frequently are used to distinguish between these diagnostic possibilities. As treatment or prophylaxis for HO, either a nonsteroidal antiinflammatory drug (such as indomethacin), a diphosphonate (such as ethane-1-hydroxy-1,1-diphosphate), or local radiation therapy is recommended. Before therapy begins, bone scanning may be requested to confirm the diagnosis of HO. In addition, surgical resection of HO is used to preserve joint mobility; however, HO is likely to recur and possibly progress if resection is undertaken before the lesion has become mature. With a view toward avoiding recurrent HO and other operative complications, serial quantitative bone scans are used as an aid to time surgical intervention.