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.

Impact of three-phase bone scintigraphy on the diagnosis and treatment of complex regional pain syndrome type I or reflex sympathetic dystrophy.

OBJECTIVE: To determine the impact of three-phase bone scintigraphy (TPBS) on the diagnosis and management of complex regional pain syndrome type I (CRPSI) or reflex sympathetic dystrophy (RSD). SUBJECTS AND METHODS: Twenty consecutive patients with a recent clinical evidence of CRPSI were referred for TPBS as part of their routine management plan. All patients underwent neurological examinations with special attention to the evaluation of clinical features of vasomotor, sudomotor, motor and sensory dysfunction. Patients were followed prospectively. When both the clinical and TPBS results supported the diagnosis of CRPSI, patients were started on treatment. RESULTS: Of the 20 patients, TPBS supported the diagnosis of RSD in 9 who were treated with steroids and physiotherapy. Complete follow-up was available for 7 of them and all had a satisfactory response to treatment. For the remaining 11 patients RSD was diagnosed clinically but not confirmed by TPBS. On follow-up there was no evidence that TPBS failed to identify RSD in these 11 patients. CONCLUSION: The results indicate that TPBS confirmed the clinical diagnosis of RSD, and, more importantly, had a significant impact on its management.

Renography within 1 hour of renal transplantation: technical feasibility and clinical utility.

OBJECTIVE: Renographies obtained within 1 h of renal transplantation were studied prospectively to evaluate their technical feasibility and potential clinical impact on successful treatment of immediate posttransplantation complications such as arterial or venous thrombosis, which require prompt diagnosis and management. SUBJECTS AND METHODS: During December 1996 to December 1998, 127 renal transplants were performed. Ninety-four patients had complete renographic studies within 1 h of surgery. It was not possible to perform renography on 26 patients who were not sent to the Department of Nuclear Medicine within 1 h of transplant and 7 other patients who could not undergo a complete renogram because of their postoperative condition. RESULTS: There was no complication attributed to transporting patients to the Department of Nuclear Medicine for these studies so soon after surgery. Of the 94 renographies obtained immediately following transplant surgery 46 were abnormal. However, when compared with the usual policy of obtaining baseline renograms between 12 and 72 h after surgery, treatment was changed for only 2 patients. Radionuclide renography within 1 h of transplant surgery was technically feasible. CONCLUSION: Based on the results of this study the clinical utility of obtaining renography within 1 h posttransplant was minimal and hence we recommended that it should not be performed routinely but could be used on an individual basis when imminent intervention is highly likely.

Technical errors in planar bone scanning.

Optimal technique for planar bone scanning improves image quality, which in turn improves diagnostic efficacy. Because planar bone scanning is one of the most frequently performed nuclear medicine examinations, maintaining high standards for this examination is a daily concern for most nuclear medicine departments. Although some problems such as patient motion are frequently encountered, the degraded images produced by many other deviations from optimal technique are rarely seen in clinical practice and therefore may be difficult to recognize. The objectives of this article are to list optimal techniques for 3-phase and whole-body bone scanning, to describe and illustrate a selection of deviations from these optimal techniques for planar bone scanning, and to explain how to minimize or avoid such technical errors.

Nonosseous abnormalities on bone scans.

Although bone scanning is a test primarily concerned with skeletal abnormalities, important nonosseous findings are occasionally present on the images. To gauge the significance of such nonosseous uptake and, in particular, to determine whether these findings contain useful diagnostic information, the technical and medical staff in nuclear medicine must recognize the various patterns of nonbony uptake and understand their causes. The objectives of this article are to demonstrate the appearances of nonosseous uptake on bone scans, to categorize the forms of soft-tissue uptake, to emphasize technical artifacts leading to soft-tissue uptake, and to highlight the clinical significance of pathologic soft-tissue uptake.

Dextrose solutions yield radiochemical impurities: the "sweet" scans.

OBJECTIVE: If additional chemicals are inadvertently introduced in the preparation of radiopharmaceutical kits, radiochemical impurities may be formed. We report our experience with erroneously diluting (99m)Tc-pertechnetate eluate with 5% dextrose solution rather than normal saline during the preparation of (99m)Tc-tetrofosmin, (99m)Tc-methylene diphosphonate (MDP), (99m)Tc-stannous colloid, and (99m)Tc-mebrofenin. METHODS: Scintigrams for 3 of the 4 radiochemicals unintentionally prepared with 5% dextrose were found to have an altered biodistribution. Therefore, radiopharmacy procedures for the day were reviewed, and instant thin-layer chromatography (ITLC) was performed. RESULTS: Scintigrams showed an altered biodistribution consistent with an impurity. Review of procedures that day uncovered the error of using 5% dextrose to dilute the (99m)Tc eluate. The altered biodistribution on (99m)Tc-stannous colloid, (99m)Tc-MDP, and (99m)Tc-mebrofenin scintigrams consisted of cardiac blood-pool activity (possibly as a result of slow clearance of (99m)Tc-dextrose), soft-tissue background activity (possibly as a result of interstitial distribution of (99m)Tc-dextrose), renal and bladder activity (possibly as a result of renal elimination of (99m)Tc-dextrose), and gallbladder activity (possibly as a result of hepatobiliary excretion of (99m)Tc-dextrose). Both scintigrams and ITLC showed no evidence of impurities for the (99m)Tc-tetrofosmin prepared using 5% dextrose. CONCLUSION: Unintended preparation of radiochemicals with 5% dextrose rather than normal saline often results in the production of impurities, possibly (99m)Tc-dextrose. Because some but not all commercial radiochemical kits prepared with 5% dextrose will suffer this fate, nuclear medicine physicians reviewing the day's images will be confronted with a confusing combination of expected and grossly abnormal findings.

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.

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.

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.

Nitric oxide synthase as a marker in colorectal carcinoma.

Elevated inducible nitric oxide synthase (iNOS) activity has been found in 60 per cent of colon adenomas and 20 to 50 per cent of adenocarcinomas. We postulated that high levels of iNOS may increase the invasive and metastatic potential of colon carcinoma and could be indicative of survival potential. Data were reviewed for 52 patients with colorectal carcinoma diagnosed in 1991 and 1992. Specimens were stained for iNOS and catalogued as low-activity staining (LAS) or high-activity staining (HAS) on the basis of visual evaluation by three pathologists. Thirty patients were LAS and 22 HAS. Age, sex, preoperative carcinoembryonic antigen, tumor and nodal status, and American Joint Committee on Cancer staging were not different between groups. Forty-six per cent of the HAS group remained alive after 5 years versus 71 per cent in the LAS group. Survival was significantly lower and metastatic status significantly higher in the HAS group. Results indicated that iNOS activity may be a prognostic indicator of long-term survival potential after treatment for colon cancer. In addition results suggested that metastasis was greater in colon carcinoma specimens that maintain an activated iNOS and that these cells clinically react more aggressively. Conclusions are tempered by the fact that results were based on a limited sample size.

Colonoscopy in octogenarians and older patients.

INTRODUCTION: Colonoscopy in the elderly has been considered by many to be risky because of mechanical bowel preparation and dehydration, electrolyte disturbances, conscious sedation, and hypoxic complications. We hypothesized that colonoscopy in octogenarians and older patients is a safe procedure. MATERIALS AND METHODS: A retrospective review of 803 patients who underwent colonoscopy from January 1997 to October 1997 was performed. The patients were grouped by age: group A (17-49 years) had 166 patients (20%); group B (50-79 years) had 534 patients (67%); and group C (80 years and older) had 103 patients (13%). Results were considered significant at p value less than 0.05 unless otherwise noted. RESULTS: Blood in the stool (84%) and history of colonic vascular disease (5.8%) were the most common indication in group C (84%). Colonoscopy was used in group A (18%) more often than in the other groups to rule out inflammatory bowel disease. History of colon polyps was a more common indication in group B (20%) than in the other groups. Group A had a significantly higher incidence of normal examinations (84%) and diagnosis of inflammatory bowel disease (14%). Group B had a higher incidence of polyps than the other groups. Group C had the highest incidence of vascular disease (15%). Diverticular disease and carcinoma were more common in groups B (37%) and C (52%). The amount of sedation in the groups did not significantly differ. Completion of the colonoscopy to the cecum or anastomotic sites did not differ among the groups (p > 0.05), nor did complication rates among groups (p > 0.05). CONCLUSIONS: Colonoscopy is safe in octogenarians and older patients. Age does not, by itself, confer an increased risk to the procedure.

Traumatic carotid artery dissection: a significant incidental finding.

Blunt traumatic carotid artery dissection remains controversial in terms of diagnostic screening, reported incidence, and management. Treatment options include observation, anticoagulation and endovascular stenting, and aggressive surgical repair of the carotid artery injury. Blunt traumatic carotid artery dissections were reviewed through a retrospective study of trauma registry records. Seven patients were identified from 3342 patients over 3 years. Six patients were identified incidentally during magnetic resonance imaging (MRI) cervical spine/brain screening and one patient during angiographic evaluation for possible penetrating neck injury without MRI/magnetic resonance angiography (MRA). A total of 189 patients underwent MRI screening over this 3-year period, demonstrating a relative incidence of 3.7 per cent, contrasting with the reported incidence of 0.08 to 0.4 per cent for all trauma patients. All seven patients suffered severe head injuries (mean Glasgow Coma Score = 4.7) requiring mean intensive care unit and hospital stays of 15.6 and 23.7 days, respectively. None of the patients showed evidence of stroke with CT scanning on presentation. None of the patients demonstrated clinical focal neurologic signs or symptoms indicating carotid injury or stroke. Six patients survived their acute trauma and were discharged to rehabilitation after initiation of observation (one patient) or anticoagulation (five patients). All six patients showed neurological improvement without deterioration clinically or radiographically. In conclusion we propose early aggressive screening through MRI/MRA of severely injured patients to detect occult carotid artery dissections. Conservative medical treatment for this occult injury has been effective in this series of patients.

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.

Biodistribution of 99Tcm-labelled 5-thio-D-glucose.

We studied the biodistribution and tumour localization of 99Tcm-labelled-5-thio-D-glucose (99Tcm-TG). 5-Thio-D-glucose was labelled with 99Tcm by direct stannous ion reduction. The biodistribution of 99Tcm-TG was investigated in normal rabbits and in mice bearing experimental tumours. In rabbits, the plasma and clearance of 99Tcm-TG was 14.5 +/- 2.0 and 11.3 +/- 3.0 ml.min-1 respectively. Urinary excretion at 1 h was 53 +/- 5%. 99Tcm-TG was injected intravenously in mice bearing MC26 colon carcinoma and tissue samples were analysed by gamma scintillation counting at various times. Uptake of 99Tcm-TG in tumour at 1 and 3 h was 1.6 +/- 0.3% and 1.2 +/- 0.3%; the tumour to muscle ratios were 2.7:1 and 4:1 respectively. The autoradiographic biodistribution of 99Tcm-TG in MX-1 human breast xenografted nude mice showed more persistent tumour uptake of 99Tcm-TG than 14C-2-deoxyglucose (14C-DG). 99Tcm-TG accumulated in the centre of the tumours; 14C-DG was decreased in this central region probably because of zones of infarction on necrosis. The discordance between the tumour uptake of 99Tcm-TG and 14C-DG indicates that 99Tcm-TG does not act like a glucose analog, suggesting 99Tcm-TG avidity for zones of infarction or necrosis. The further study of 99Tcm-TG in tumours and ischaemic injury is warranted.