Indication of doxorubicin cardiotoxicity by impairment of 131I-pIPPA utilization

The present study was designed to evaluate if doxorubicin (D) can impair myocardial fatty acid utilization. To this end we studied the myocardial utilization of ¹³¹I-pIPPA in untreated (Co, n=6) and D (20 mg/kg intraperitoneal) treated rats. D was given 24 h (24 D, n=6) and 48 hours (48 D, n=6) before tracer administration. One min after i.v. ¹³¹I-pIPPA (50 μCi) injection, the hearts were rapidly removed, frozen in liquid nitrogen, weighed, and counted. Following lipid extraction of homogenized heart extracts 131 I radioactivity distribution was analyzed by thin-layer chromatography (TLC). In additional rat experiments, high energy phosphates (12 rats/group) and carnitine (20 rats/group) were determined enzymatically in heart extracts. The mean pIPPA uptake in rat heart (%dose/g) was 2.49 in Co, 1.74 in 24 D, and 2.36 in 48 D rats. Usually five peaks were separated by TLC, that with a mean Rf value of 0.92 corresponding to ¹³¹I-pIPPA, the remaining four representing catabolites of pIPPA metabolism. The mean relative amount of unmetabolized ¹³¹I-pIPPA as compared to the sum of ¹³¹I-pIPPA catabolites was less in Co than in 24 D or 48 D rats (P<0.05) (\(\bar x\): 46.5% vs 72.4% vs 59.4%, respectively). The mean carnitine content of heart extracts was higher in Co (0.55 μM/g) than in D treated rats (24 D, 0.42 μM/g; 48 D, 0.46 μM/g) P<0.05). The total amount of higher energy phosphates was not different between the groups. However the mean ATP/AMP ratio was higher in Co (35.9) than in 24 D (22.3) or 48 D (27.1) rats (P<0.05). We conclude that D therapy is accompanied by a partial reversible impairment in myocardial pIPPA utilization, possibly mediated by carnitine deficiency. Thus, ¹³¹I-pIPPA might be useful in patients on D therapy to evaluate eventual D-induced effects on myocardial fatty acid utilization.

     

Dynamic 123I-HDA myocardial scintigraphy after aortocoronary bypass grafting

In an attempt to evaluate the dynamics of fatty acid metabolism after aortocoronary bypass grafting (ACBG), ten patients were investigated after ACBG by ¹²³I-HDA myocardial scintigraphy. Tracer kinetics were followed for 90 min and compared to those of 36 nongrafted patients with different underlying heart diseases, including healthy volunteers. Regional analysis and monoexponential curve fitting were used to evaluate t _1/2 (half-life of the early period of tracer elimination); biexponential curve analysis was used to calculate Ca/Cb, the ratio of a fast and a slow component of tracer elimination. Rest and stress MUGA-RNV served as discriminating parameters to discern between patient groups with normal and abnormal ventricular function. Group I (normal controls) encompassed ten patients with normal ventricular function, including three after ACBG, and group II seven patients after ACBG and with abnormal ventricular function. Group III had coronary artery disease (CAD) documented by angiography, and group IV by prior myocardial infarction (MI). Group V included patients with cardiomyopathy (CMP). Regional analysis of group II revealed no significant differences to control regions (Gr I) for t _1/2 or Ca/Cb, but showed for Ca/Cb a nonsignificant shift toward group III values. However, group II differed significantly from group III and V. Three patients with normal ventricular function after ACBG showed elimination values that were all well within the range of completely normal individuals. Thus our data support the assumption that a normal function is indicative of a normal metabolism. Following myocardial fatty acid metabolism during rest might be a helpful noninvasive tool for etiologic differentiation of disturbed ventricular function.

     

Prognostic value of myocardial MIBG scintigraphy findings in patients with cardiomyopathy--importance of background correction for quantification of MIBG activity

OBJECTIVE: To assess the prognostic value of I-123 metaiodobenzylguanidine (MIBG) scintigraphy findings, and establish the most appropriate method for calculating myocardial MIBG activity in patients with left ventricular dysfunction due to cardiomyopathy (CM). METHODS: Predictors of cardiac death related to progressive heart failure (HF) were examined in 150 patients with CM (80 patients with idiopathic CM and 70 patients with ischemic CM). All patients underwent MIBG scintigraphy at rest and other hemodynamic studies when their clinical status was stable. MIBG scintigrams were obtained 15 minutes and 4 hours after the injection of the isotope. The parameters for quantification of myocardial MIBG activity were heart/mediastinal activity ratio (H/M) and myocardial washout rate (WR). The WR was calculated with and without background (BG) correction. RESULTS: The WR showed better correlation with plasma norepinephrine and left ventricular ejection fraction after BG correction. During a mean follow-up period of 33 +/- 9 (7 to 54) months, 12 patients died due to HF; 7 patients due to progressive HF and 5 patients due to sudden cardiac death. Cox regression analysis indicated, the H/M and the WR with and withoutBG correction, were significant predictors of cardiac death (Wald chi-squared value: H/M [ 15 min] = 9.7, H/M [4 hr] = 19.5, WR with BG correction = 29.9, WR without BG correction = 12.6). WR prognostic value was better after BG correction, and a high WR with BG correction was the only independent predictor of cardiac death (relative risk [RR] = 1.174, p < 0.0001). CONCLUSIONS: Accelerated WR is a powerful predictor of the patient's prognosis and BG correction is essential for calculating WR.     

No difference in plantar flexion maximal exercise power output between men and women

Background

Maximal oxygen consumption \( \dot{V}O_{{2{\text{MAX}}}} \) can be lower in women compared to men during traditional, systemic exercise even when corrected for differences in fat free mass (FFM). One potential source for lower \( \dot{V}{\text{O}}_{{2{\text{MAX}}}} \) might be inherent differences in muscle in men and women. Exercising isolated muscle such as plantar flexion provides the opportunity to study muscle function independent of systemic O₂ delivery limitations. It was hypothesized that women would have lower plantar flexion power output (PO) than men even when corrected to calf FFM.

Methods

Maximum \( \dot{V}{\text{O}}_{2} \) and PO were measured during graded treadmill exercise and PO during plantar flexion exercise in men and women.

Results

During maximal treadmill exercise, men had greater absolute \( \dot{V}{\text{O}}_{2} \) and PO. When expressed relative to FFM, there was no difference in PO at maximum between sexes, but \( \dot{V}{\text{O}}_{{2{\text{MAX}}}} \) was still greater in men. During maximal plantar flexion exercise, men demonstrated greater absolute PO, but this difference between sexes was eliminated when PO was expressed relative to calf FFM.

Conclusion

Healthy women do not demonstrate inherently lower muscle PO. Lower maximal \( \dot{V}{\text{O}}_{2} \) per FFM measured during treadmill exercise in women than men appears due to factors other than differences in muscle aerobic capacity.

     

Impact of single and multiple sets of resistance exercise in type 1 diabetes

To examine glycemic and glucoregulatory responses to resistance exercise (RE) sessions of different volume in type 1 diabetes (T1DM). Eight T1DM (seven males: one female; age: 38 ± 6 years, HbA_1C: 8.7 ± 1.0%/71 ± 11 mmol/mol) attended the research facility fasted and on four separate occasions, having taken their usual basal insulin, but omitted morning rapid‐acting insulin. Participants completed a 1SET (14 min), 2SET (28 min), 3SET (42 min) RE session (eight exercises × 10 repetitions) at 67 ± 3% one‐repetition‐maximum followed by 60‐min recovery, or a resting trial (CON). Venous blood samples were taken before and after exercise. Data (mean ± SEM) were analyzed using repeated‐measures analysis of variance (P ≤ 0.05). RE did not induce hypoglycemia (BG < 4 mmol/L). During recovery, blood glucose (BG) concentrations remained above pre‐exercise after 1SET (15–60 min, P < 0.05) and 2SET (0–60 min, P < 0.05) but comparable (P > 0.05) with pre‐exercise after 3SET. BG_{IAUC(area‐under‐curve)} (mmol/L/60 min) was greater after 1SET and 2SET vs CON (1SET 103.6 ± 36.9 and 2SET 128.7 ± 26.1 vs CON ?24.3 ± 15.2, P < 0.05), but similar between 3SET and CON (3SET 40.7 ± 59.3, P > 0.05). Under all trials, plasma creatine kinase levels at 24 h post‐exercise were similar (P > 0.05) to pre‐exercise. RE does not induce acute hypoglycemia or damage muscle. BG progressively rose after one and two sets of RE. However, inclusion of a third set attenuated exercise‐induced hyperglycemia and returned BG to that of a non‐exercise trial.     

Radioiodination of nicotine with specific activity high enough for mapping nicotinic acetylcholine receptors

A novel radiochemical method is presented to synthesize 5-[¹²³I/¹²⁵I/¹³¹I]-dl-nicotine by radioiodination of 5-bromonicotine. Radioiodination of the precursur 5-dl-bromonicotine was achieved using a copper (I)-assisted nucleophilic exchange reaction in the presence of reducing agent. The reaction conditions were optimized by varying pH, concentration of Sn(II) salt, ascorbic acid, Cu(I)chloride and reaction temperature. After purification by high-performance liquid chromatography the radiochemical purity of the product exceeded 98%, with a radiochemical yield of 55% and a specific activity ≥5 GBq/µmol. Specific binding of the iodinated nicotine was demonstrated in rat brain by autoradiography. The radioactivity from the specific structures was displaced by an excess of non-radioactive nicotine (10^?3 M) withK _D andB _max of 13.1±7.8 nM and 22±2.7 fmol/mg protein and unspecific binding of about 40%. The in vivo distribution of 5-[¹³¹I]iodonicotine was determined in 20 female Wistar rats at various time intervals of 15 s to 90 min post injection (p.i.) by well counting and autoradiography. Brain activity peaked within 0.5 min p.i., and then showed a biexponential washout. Initially, activity within the cerebral cortex exceeded that of the cerebellum by a factor of 1.5–2.0. It was also increased in the striatum and thalamus. However, as soon as 15 min p.i. activity was almost homogeneously distributed. In conclusion, synthesis of 5-iodo-dl-nicotine (labelled with¹³¹I,¹²⁵I or¹²³I, respectively) with appropriately high specific activity for receptor studies was achieved and specific binding to nicotine receptors in rat brain was demonstrated; following intravenous injection, however, there is considerable unspecific binding, obviously due to highly flow-dependent tissue retention.     

Localization of IBF as a D-2 dopamine receptor imaging agent in nonhuman primates

Preliminary study of iodine-123 labeled IBF, (S)-5-iodo-7-N-[(1-ethyl-2-pyrrolidinyl)methyl] carboxamido-2, 3-dihydrobenzofuran, has demonstrated the potential of using this agent to evaluate the status of the CNS D-2 dopamine receptor in humans. To further characterize this ligand and evaluate single-photon emission tomography (SPET) quantitation, a detailed biodistribution study in monkeys (Macaca fascicularis) with ¹²³I- and ¹²⁵I-IBF was performed. The dual tracer was simultaneously injected for in vivo imaging, biodistribution, and ex vivo autoradiography in the same monkey. After the injection, SPET data (10 min/frame × 15) were collected with a triple-head gamma camera. Dynamic imaging data indicated that IBF localized in basal ganglia (BG) with a half life of 90-120 min. Other regions, i.e., cerebellum (CB) and cortex (CX), showed very low uptake. At 2.2 h after the injection, the monkey was sacrificed. Organ distribution data indicated that, as expected, there was a significant uptake in basal ganglia (0.029% ID/g), and the BG/CB and BG/CX ratios were 17.8 and 14.2 respectively. Lower ratios were obtained from SPET image analysis (BG/CB=3.5 at 2.5h). The eye uptake was observed with SPET, but was only quantified on autoradiograms with significant uptake (0.017% ID/g). Autoradiography of the eye demonstrated that predominant uptake was localized in the ciliary body and the choroid. The selective retention and high BG/CB ratio of ¹²³I-IBF make it a useful agent for in vivo D-2 dopamine receptor imaging with SPET. Correspondence to: H.F. Kung     

Dipyridamole combined with symptom-limited exercise for myocardial perfusion scintigraphy: image characteristics and clinical role

Although dipyridamole can be used with myocardial scintigraphy to demonstrate reversible perfusion defects, combining exercise with the pharmacologic tool could improve image quality and information yield. The incidence of perfusion defects and the quality of thallium 201 images were reviewed in a series of 820 patients who had been assigned to a specific stress-test mode. Supine bicycle exercise alone was used (group 1) where no pharmacologic or physical factors (e.g., beta-blockers, arthritis) limited performance; otherwise, intravenous dipyridamole was followed by symptom-limited exercise (group II). Angiographic correlation was available in 57 patients in group I, and in 158 in group II; of these, 109 performed significant exercise ( 3 min at increasing workloads) following dipyridamole (group II A), whereas in 49 (group IIB) the exercise phase following dipyridamole was truncated. All test-mode groups were similar with respect to the incidence of ST segment depression during testing, patient throughput, and the sensitivity of perfusion defects. Chest pain and reversible defects were induced more frequently in group II than in group I. In group II A, splanchnic background activity was lower (P < 0.001) than in group II B, and the false-positive rate tended to be lower. Thus, combining exercise with dipyridamole in patients with non-cardiac limitations to exercise enabled the achievement of optimal results for perfusion scintigraphy.     

The metabolism of 15-p-[123I]-iodophenylpentadecanoic acid in a surgically induced canine model of regional ischemia

The purpose of this study was to examine the longitudinal effect of gradual coronary occlusion on regional myocardial metabolism of 15-p-¹²³I-iodophenyl pentadecanoic acid ([¹²³I]IPPA). Adult dogs were imaged using [¹²³I]IPPA and planar gamma imaging. A thoracotomy was performed and an ameroid constrictor of appropriate size permanently positioned on the left anterior descending coronary artery. The dogs were imaged after injection of 3–5 mCi [¹²³I]IPPA at various times over a 2-week period. With imaging on days 7 and 14, the dogs were paced at a rate of 185. Time-activity curves were generated and t_1/2 values calculated using monoexponential curve fitting. Results indicate a significant increase in t_1/2 between control and 14 days after surgery in the apical wall (29±7 to 53±18 min;P<0.05). Although there was also an increased t_1/2 in the lateral wall, this was not significant (27±8 to 78±99 min;P > 0.05). There was no significant change in t/12 in the septal wall (27±9 to 33±8 min;P>0.05). We conclude that [¹²³I]IPPA is a useful indicator ofThis work was supported by the British Columbia Heart Foundation     

Preoperative evaluation of hepatic functional reserve following hepatectomy by technetium-99m galactosyl human serum albumin liver scintigraphy and computed tomography

It is extremely important to have a good grasp of the acceptable limit of hepatectomy before operation because postoperative liver failure can take a fatal course; however, baseline data on the limit of hepatectomy have not been clearly defined. We therefore evaluated and compared the predicted remnant liver function obtained by computed tomography(CT) and technetium-99m diethylenetriamine penta-acetic acid-galactosyl human serum albumin (^99mTc-GSA) liver scintigraphy in order to obtain precise data regarding remnant liver function before hepatectomy. We investigated 20 patients undergoing hepatectomy using the clearance rate of indocyanine green (KICG) as a parameter, and compared the predicted postoperative KICG obtained by CT and by transaxial single-photon emission tomographic (SPET) images acquired by ^99mTc GSA liver scintigraphy before hepatectomy. In GSA studies, based on time-activity curves for the heart and liver, we compared HH15 (heart activity at 15 min divided by heart activity at 3 min), LHL15 (liver activcity at 15 min divided by heart plus liver activity at 15 min) and K_L (obtained from the time-activity curve for the liver) in 103 patients. In 58 patients without increased serum bilirubin, K_L was compared with KICG. In four patients, occlusion of the right portal vein was performed with the aim of carrying out secondary hepatectomy, and changes in liver volume were compared between CT and ^99mTc GSA liver scintigraphy. The correlation coefficient between the postoperative KICG predicted by CT and the actual postoperative KICG was rather poor, at r = 0.569 (P<0.05); that between the postoperative KICG predicted by ^99mTc GSA liver scintigraphy and the actual postoperative KICG was good, at r = 0.788 (P<0.01); correlations between K_L and HH15 and between K_L and LHL15 in 103 patients were very good or good, at r = 0.906 (P<0.001) and r = 0.807 (P<0.001), respectively, and that between K_L and KICG in 58 patients was very good, at r = 0.916 (P<0.001). In all four cases of right portal vein occlusion, the remnant liver volume ratio was markedly increased after occlusion in GSA compared with CT, and the postoperative KICG predicted by GSA after occlusion was closer to the actual postoperative KICG than that predicted by CT. It is concluded that ^99mTc GSA liver scintigraphy is useful for predicting remnant liver function before hepatectomy and for evaluating changes in regional liver function after occlusion of the portal vein unilaterally. Received 20 March and in revised form 24 June 1998     

Measurement of effective renal plasma flow: a comparison of methods

We have compared two in vitro methods and three variations of kidney background (BG) subtraction within a gamma camera method (41 examinations, 31 patients) for determination of effective renal plasma flow (ERPF) using 131I orthoiodohippurate (OIH). Method I: plasma samples at 20 and 45 min after OIH injection, ERPF = dose X slope/intercept; Method II: 45-min plasma sample, ERPF = -51.1 + 8.21x + 0.019x2, x = dose/45-min plasma activity/I. Individual kidney and total ERPF were determined from gamma camera (GC) methods using renal uptake 1-2 min after injection. All methods were compared against Method I (previously validated against paraaminohippurate (PAH) clearances). Method II, which requires one blood sample is more accurate than GC methods. GC methods are insensitive to operator variability in placement of renal and BG regions of interest. They may be useful to follow changes in relative or total ERPF, but accurate depth correction of renal data is suggested. In vitro, blood sample-based methods are more accurate.     

Transcriptome analysis of reproductive-stage Arabidopsis plants exposed gamma-ray irradiation at various doses

Purpose: Gamma rays (GR) induce significant changes in the structure and expression of genes involved in the regulation of diverse biochemical and physiological processes. Arabidopsis plants exhibit different growth and development patterns in response to exposure to GR. The effects on gene expression of different radiation doses of GR (100 and 800?Gy) administered to Arabidopsis plants were examined at the reproductive stage.

Materials and methods: We irradiated 26-day-old plants with three replications [developmental stages 5.1–6.0, according to Boyes et al. (2001 Boyes DC, Zayed AM, Ascenzi R, McCaskill AJ, Hoffman NE, Davis KR, Gorlach J. 2001. Growth stage-based phenotypic analysis of Arabidopsis: A model for high throughput functional genomics in plants. Plant Cell. 13:1499–1510.[Crossref], [PubMed], [Web of Science ®] , [Google Scholar])] using a GR irradiator (60 Co, ca. 150 TBq capacity, Atomic Energy of Canada Limited, Ontario, Canada) at the Korea Atomic Energy Research Institute. Plants were treated with 100, 200, 300, 400, 800, 1200, 1600, or 2000?Gy, and the doses were made from varying the distance to the source.

Results: We conducted a high-throughput screening analysis and detected 883?GR-responsive genes that showed significant changes; these were involved in several putative metabolic pathways related to biotic stress. Additionally, five overrepresented cis-regulatory elements were identified in the 1-kb upstream regions of GR-responsive genes by using motif enrichment analysis. We also detected three GR-responsive genes associated with stamen development and confirmed their co-regulation with functionally interacting genes.

Conclusions: This finding suggests that a network-based analysis is a viable approach to identify significant GR-responsive genes associated with the reproductive stage of Arabidopsis. Our results provide further insights into the complex biological systems involved in the response to different doses of GR in plants.     

The use of 123I-labeled heptadecanoic acid (HDA) as metabolic tracer: Preliminary report

The feasibility of using ¹²³I-heptadecanoic acid (HDA) as a metabolic tracer was studied. Different administration routes of HDA were compared. An intracoronary bolus injection was given to calves (n=3), and an intravenous injection was given to patients (n=4). In addition, we examined the influence of 4-h halothane anesthesia in calves and in patients the impact of an insulin (1.5 IU/kg)+ glucose (1.5 g/kg) infusion on the myocardial kinetics of HDA. Data were accumulated with a scintillation probe in calves (t=50 min) and a gamma camera in patients (t=70 min). In calves after an intracoronary bolus injection of HDA the myocardial time-activity curve could be described by two exponentials. The mean elimination halftime of the initial phase (t _a 1/2) was 7.3 min and that of the second phase (t _b 1/2) was 35 min. The ratio of the size of the initial and second component at t _o was 0.93. Halothane anesthesia prolonged the elimination half-times and reduced the component ratio. The biphasic behavior of the myocardial time-activity curve was maintained in patients after intravenous administration of HDA under basal conditions (initial t _a 1/2=8.4 min). However, during infusion of insulin+glucose the decline in the myocardial activity was prolonged and monoexponential. This data shows that insulin glucose, interfering with fatty acid metabolism, influences the myocardial washout of HDA, and thus support its use as a metabolic tracer.     

Resting muscle sympathetic nerve activity,cardiac metaiodobenzylguanidine uptake,and exercise tolerance in patients with left ventricular dysfunction

Background  Sympathetic nerve overactivity and reduced exercise tolerance are characteristic features of patients with heart failure. However, to what extent sympathetic nerve overactivity contributes to limiting exercise tolerance has not been clearly defined. Methods  Myocardial iodine 123-metaiodobenzylguanidine (MIBG) scintigraphy, muscle sympathetic nerve activity (MSNA), and cardiopulmonary exercise testing were performed within 3 days in 30 patients with left ventricular dysfunction (LVD). Cardiac sympathetic nerve activity was estimated using H/M ratio and washout rate (WR) of 123I-MIBG imaging. MSNA was recorded by microneurography. Results  The patients with peak VO₂ < 20 mL/minute/kg (group II, n = 15) had significantly higher MSNA and WR, and lower H/M ratio than those with peak VO₂ ≧ 20 mL/minute/kg (group I, n = 15) (P < .05). Peak VO₂ had negative correlations with MSNA and WR (r = 0.58, 0.56), and positive correlations with early H/M ratio and delayed H/M ratio (r = 0.71, 0.75) in group II. Moreover, MSNA had negative correlations with early H/M ratio and delayed H/M ratio (r = 0.78, 0.66), and a positive correlation with WR (r = 0.79) in group II. However, similar relations were not found in group I. Conclusions  A link between cardiac and peripheral sympathetic nerve activities contributed to limiting exercise tolerance in patients with LVD patients and reduced exercise tolerance. See related editorial, doi:     

Simulated games activity vs continuous running exercise: A novel comparison of the glycemic and metabolic responses in T1DM patients

To compare the glycemic and metabolic responses to simulated intermittent games activity and continuous running exercise in type 1 diabetes. Nine patients (seven male, two female; 35 ± 4 years; HbA1c 8.1 ± 0.2%/65 ± 2 mmol/mol) treated on a basal‐bolus regimen completed two main trials, a continuous treadmill run (CON) or an intermittent running protocol (INT). Patients arrived to the laboratory fasted at ～ 08:00 h, replicating their usual pre‐exercise meal and administering a 50% reduced dose of rapid‐acting insulin before exercising. Blood glucose (BG), K⁺, Na⁺⁺, pH, triglycerides, serum cortisol and NEFA were measured at baseline and for 60 min post‐exercise. Interstitial glucose was measured for a further 23 h under free‐living conditions. Following exercise, BG declined under both conditions but was less under INT (INT ?1.1 ± 1.4 vs CON ?5.3 ± 0.4 mmol/L, P = 0.037), meaning more patients experienced hypoglycemia (BG ≤ 3.5 mmol/L; CON n = 3 vs INT n = 2) but less hyperglycemia (BG ≥ 10.9 mmol/L; CON n = 0 vs INT n = 6) under CON. Blood lactate was significantly greater, and pH lower, with a temporal delay in K⁺ under INT (P < 0.05). No conditional differences were observed in other measures during this time, or in interstitial glucose concentrations during the remaining 23 h after exercise. Simulated games activity carries a lower risk of early, but not late‐onset hypoglycemia than continuous running exercise in type 1 diabetes.     

Technical variables of ACL surgical reconstruction: effect on post-operative static laxity and clinical implication

Purpose

The hypothesis was that an alteration of different surgical variables of ACL reconstruction would produce significant changes in post-operative static laxity of knee joint.

Methods

Joint laxity was acquired by a surgical navigation system for 17 patients just after graft fixation during single-bundle reconstruction with extra-articular lateral tenodesis. The analysed laxity parameters were: internal/external rotation at 30° (IE30) and 90° (IE90) of flexion, varus/valgus rotation at 0° (VV0) and 30° (VV30) of flexion and anterior/posterior displacement at 30° (AP30) and 90° (AP90) of flexion. As surgical variables, the angles between the tibial tunnel and the three planes were defined as well as the lengths of the tunnel and the relationship between native footprints and tunnels. The same analysis was performed for the femoral side. All surgical variables were combined in a multivariate analysis to assess for predictive factors between them and post-operative laxities values. To quantify the performance of each multivariate model, the correlation ratio (η ²) and the corresponding P value (*P < 0.050) have been evaluated.

Results

Multivariate analysis underlined statistically significant models for the estimation of: AP30 (η ² = 0.987; P = 0.014), IE30 (η ² = 0.995; P = 0.005), IE90 (η ² = 0.568; P = 0.010), VV0 (η ² = 0.932; P = 0.003). The parameters that greatly affected the identified models were the orientation of the tibial tunnel with respect to the three anatomical planes. The estimation of AP30, IE30 and IE90 got lower value as the orientation of the tibial tunnel with respect to transverse plane decreases. Considering the orientation to sagittal (\(\theta_{\text{SAG}}^{T}\)) and coronal (\(\theta_{\text{COR}}^{T}\)) plane, we found that their reduction provoked a decrease in the estimation of AP30, IE30 and IE90 (except \(\theta_{\text{SAG}}^{T}\) that did not appear in the estimation of AP30). The estimation of VV0 got an increase of \(\theta_{\text{SAG}}^{T}\), and \(\theta_{\text{COR}}^{T}\) which led to a laxity reduction.

Conclusion

The main finding of the present in vivo study was the possibility to determine significant effects on post-operative static laxity level of different surgical variables of ACL reconstruction. In particular, the present study defined the conditions that minimize the different aspects of post-operative laxity at time-zero after surgery.

     

External detection of regional myocardial metabolism with radioiodinated hexadecenoic acid in the dog heart

In a previous study we have demonstrated that terminally iodinated hexadecenoic acid (¹³¹I-HA) and Thallium-201 (²⁰¹Tl) are comparable in myocardial uptake and distribution in the ischemic dog heart (Westera et al. 1980). In the present study the potential value of ¹³¹I-HA was proved in determining regional myocardial metabolism in 19 dog experiments.In ten dogs, ¹³¹I-HA was administered 5 min after occlusion of a coronary artery (group II), in six dogs after a 90 min occlusion period (group III). Three dogs served as controls (group I). The turnover rates (t1/2) of ¹³¹I-HA were calculated from mono-exponential time-activity curves, obtained by external detection over ischemic and normally perfused areas during a 30 min period after IV injection of 0.7–1.5 mCi ¹³¹I-HA. The t1/2 values in ischemic regions were found to be significantly longer (group II, 25.1±2.6 min; group III, 22.6±1.8 min) than in nonischemic areas (group II, 12.5±1.8 min; group III, 14.2±1.4 min). The t1/2 values in the control dogs (group I, 13.4±1.4 min) were not significantly different from the turnover rates in the non-ischemic areas of the occluded hearts.We conclude that the study of turnover rates of radioiodinated free fatty acids allows the determination of regional myocardial metabolism and offers a means to distinguish normally perfused from ischemic myocardial tissue.     

Assessment of changes in murine tumor oxygenation in response to nicotinamide using 19F NMR relaxometry of a perfluorocarbon emulsion

The oxygen dependencies of the 19F NMR spin-lattice relaxation rates (R₁ = 1/T₁) of a perfluorocarbon emulsion sequestered in a murine tumor model has been used to evaluate nicotinamide, a radiosensitizer believed to act through enhanced tissue oxygenation. Fluorine-19 NMR spectroscopic measurements from solid Radiation-Induced Fibrosarcoma (RIF-1) tumors in C3H mice showed a statistically significant improvement in tumor pO₂ for a Nicotinamide-treated group, with a ΔpO₂ = 4.7 ± 3 torr (=mm Hg) (Mean ± SEM) at t = 60 min (P <.01), and 4.5 ± 3 at t = 70 min post intraperitoneal injection (P < 0.02) as compared with saline-treated Controls, while several other time points for which t > 30 min were significant at the P < 0.05 level. Both groups had n = 10, and the statistics were based on Student's one-tailed group t test. By comparison, in another study group where breathing gas was switched from air to 100% O₂, a statistically insignificant increase of 2 torr was realized in tumor pO₂ (n = 9). The maximal treatment effect occurs at a delay of 60 to 70 min, consistent with results obtained by other investigators using radiobiology techniques. Fluorine-19 spectroscopic relaxometry can measure therapeutically meaningful changes in in vivo tumor pO₂ and represents an improvement in expenditures of time, animal resources, and statistical power over conventional radiobiological methods.     

123I-mIBG Scintigraphy to predict risk for adverse cardiac outcomes in heart failure patients: Design of two prospective multicenter international trials

Background  ADMIRE-HF (AdreView Myocardial Imaging for Risk Evaluation in Heart Failure) consists of two identical prospective open-label, multicenter, phase 3 studies (MBG311 and MBG312) evaluating the prognostic usefulness of ¹²³I-mIBG scintigraphy for identifying subjects with heart failure who will experience a major adverse cardiac event. Methods  Subjects with NYHA class II and III heart failure and left ventricular ejection fraction ≤35% were eligible for the trials. Subjects underwent planar and SPECT ¹²³I-mIBG myocardial imaging, as well as echocardiography and gated SPECT ^99mTc-tetrofosmin myocardial perfusion imaging. Subjects are then monitored on a regular basis for 2 years. Time to first occurrence of one of the following—NYHA class progression; potentially life-threatening arrhythmic event (including ICD discharge); or cardiac death, as verified by an independent adjudication panel—will be analyzed in comparison to quantitative parameters derived from ¹²³I-mIBG imaging. The primary efficacy analysis will employ the heart/mediastinum ratio on 4-hour delayed planar imaging, while secondary efficacy analyses will examine quantitative results from both planar and SPECT ¹²³I-mIBG images, as well as from ^99mTc-tetrofosmin SPECT and echocardiography. Conclusion  The results of the ADMIRE-HF trials will provide prospective validation of the potential role of ¹²³I-mIBG scintigraphy in assessing prognosis and developing management strategies for patients with heart failure. Funding Source: GE Healthcare.