Effect of aerobic exercise training on renal responses to sodium in hypertensives

INTRODUCTION: Aerobic exercise training has been shown to improve cardiovascular function and lower blood pressure (BP) in older adults. The exact mechanism(s) by which aerobic exercise training elicits these changes are unknown; however, it is possible that changes in renal hemodynamics may play a role. PURPOSE: The present study was undertaken to examine the effect of aerobic exercise training on renal hemodynamics in older hypertensive individuals. METHODS: Renal plasma flow (RPF) and glomerular filtration rate (GFR) were determined by plasma and urinary clearances of 131I-hippuran and 99mTc-DTPA after 8 d of low (20 mEq) and high (200 mEq) Na+ diets in 31 older (63 +/- 1 yr), hypertensive (152 +/- 2/88 +/- 1 mm Hg) individuals at baseline and following 6 months of aerobic exercise training (at 75% VO2max, three times a week, 40 min per session). RESULTS: Following 6 months of aerobic exercise training, a significant increase was seen in maximal aerobic capacity (VO2max: 18.3 +/- 0.7 vs 20.7 +/- 0.7 mL.kg.min(-1), P = 0.017) as well as a significant decrease in resting systolic (152 +/- 2 vs 145 +/- 2 mm Hg, P = 0.037) and mean arterial (109 +/- 1 vs 105 +/- 1 mm Hg, P = 0.021) BP. No significant (P < 0.05) effects were seen of aerobic exercise training on RPF (208.8 +/- 12.2 vs 197.1 +/- 13.1 mL.min(-1).1.73 m(-2)), GFR (68.9 +/- 3.6 vs 69.0 +/- 3.9 mL.min(-1).1.73 m(-2)), or filtration fraction (35.3 +/- 2.3 vs 37.1 +/- 2.4%) on the low Na+ diet or RPF (210.6 +/- 12.8 vs 212.1 +/- 11.7 mL.min(-1).1.73 m(-2)), GFR (72.9 +/- 4.1 vs 77.3 +/- 4.3 mL.min(-1).1.73 m(-2)), or filtration fraction (37.1 +/- 2.5 vs 37.7 +/- 3.0%) on the high Na+ diet. CONCLUSIONS: Our results suggest that changes in renal hemodynamics do not contribute to the reduction in resting BP in older hypertensive persons.     

Inspiratory impedance effects on hemodynamic responses to orthostasis in normal subjects

BACKGROUND: Breathing through an impedance threshold device (ITD) might prove effective as a countermeasure against post-spaceflight orthostatic hypotension since it increased blood pressure (BP) and cardiac output in supine human subjects. OBJECTIVE: We tested the hypothesis that spontaneous breathing through an ITD would attenuate the reduction in stroke volume and BP during orthostasis in human subjects. METHODS: There were 19 volunteers (10 men, 9 women) who completed two 80 degrees head-up tilt (HUT) protocols with (active) and without (sham control) an ITD set to open at -7 cm H2O pressure. Heart rate (HR), stroke volume (SV), cardiac output (CO), mean arterial pressure (MAP), and total peripheral resistance (TPR) were measured non-invasively during transition from supine to HUT. RESULTS: HUT caused significant elevation in HR and reductions in SV, CO, TPR, and MAP. Hemodynamic effects of HUT were similar for sham and active ITD. Further analysis revealed a subset (n = 11) of subjects who demonstrated a > 20% decrease in SV during HUT with the sham ITD. In this subset of subjects, the ITD attenuated (p = 0.004) the %deltaSV (-22.5 +/- 3.0%) during HUT compared with the sham ITD (%deltaSV = -37.4 +/- 2.6%). There was no statistical effect of ITD use in the subgroup who demonstrated < 20% reduction in SV (-16.6 +/- 0.4%). CONCLUSIONS: Use of an ITD may provide significant protection against orthostatic compromise in individuals with greater than 20% reductions in SV, such as astronauts returning from space.     

Radiolabeling morpholinos with 90Y, 111In, 188Re and 99mTc

This laboratory is investigating morpholinos (MORF), a DNA analogue, for radiopharmaceutical applications. While we routinely radiolabel with (99m)Tc, we have now labeled MORFs with (111)In, (188)Re and (90)Y in anticipation of therapeutic studies. METHODS: A 25 mer MORF with a primary amine on the 3' equivalent end attached via a 10 member linker was conjugated with an isothiocyanate backbone derivative of DOTA (for labeling with (111)In and (90)Y) and with NHS-MAG(3) (for labeling with (188)Re and (99m)Tc). The in vitro stability of labeled MORFs were investigated and biodistribution was carried out in normal mice. RESULTS: As evident by size exclusion HPLC, ITLC and Sep-Pak analysis, all four radiolabeled MORFs were successfully radiolabeled. In each case, the labeled MORFs showed one sharp peak in HPLC that shifted completely to earlier retention times following addition of a polymer conjugated with the complementary MORF. In saline at room temperature and in 37 degrees C serum, the radioactivity profile of (111)In, (188)Re and (99m)Tc was unchanged over 48 h while over the same period, the (90)Y profile showed a pronounced lower molecular weight peak which did not shift and was shown to be most probably due to (90)Y-DOTA resulting from radiolysis. In addition, the recovery of (188)Re on HPLC decreased as samples aged probably due to oxidation to perrhenate which was retained by the HPLC column. The biodistributions at 1, 3 and 6 h in normal mice showed no important differences among all four labels with the exception that levels of radioactivity in stomach and thyroid were higher in the case of (188)Re due to in vivo oxidation of the radiolabel to perrhenate. CONCLUSIONS: When radiolabeled with DOTA, (90)Y-labeled MORF showed increased instabilities relative to that of (111)In and when radiolabeled with MAG(3), (188)Re showed in vitro and in vivo instabilities compared to (99m)Tc, but all labels were still largely intact after 48 h in saline or serum. Possibly because of the rapid clearance of MORFs, no important differences in biodistribution among (90)Y, (111)In and (99m)Tc labels were evident in normal mice. These strategies for labeling MORF with (90)Y and (188)Re therefore appear to be suitable for therapeutic applications although both show some evidence of instabilities.     

Diagnosing variant Creutzfeldt-Jakob disease with the pulvinar sign: MR imaging findings in 86 neuropathologically confirmed cases

BACKGROUND AND PURPOSE: Variant Creutzfeldt-Jakob disease (vCJD) is a rare but important cause of dementia and death in young patients and is causally linked to bovine spongiform encephalopathy. Symmetrical hyperintensity in the pulvinar (posterior) nuclei of the thalamus (pulvinar sign) on brain MR images was described as a specific, noninvasive, diagnostic sign of vCJD in a previous small series. This purpose of this larger study was to evaluate this sign prospectively and further define the MR imaging characteristics of vCJD. METHODS: As part of the ongoing surveillance program in the United Kingdom, MR images of suspected cases of vCJD were collected during a 6-year period. All available images were assessed prospectively by one observer for the presence of the pulvinar sign. Images of neuropathologically confirmed cases were then assessed independently by two neuroradiologists for the degree of hyperintensity of the pulvinar on images of different MR sequences, and for the presence of abnormal hyperintensity in other areas of the brain. Discrepancies were reviewed jointly and a consensus opinion formed. RESULTS: Prospective analysis identified the pulvinar sign in 74 of 82 cases of vCJD. In the retrospective study, the pulvinar sign, as defined by hyperintensity of the pulvinar relative to the anterior putamen, was present on seven (9%) of 75 T1-weighted, 77 (71%) of 108 T2-weighted, 47 (81%) of 58 proton density-weighted, and 30 (100%) of 30 fluid-attenuated inversion-recovery (FLAIR) images. Diffusion-weighted images were available in two cases and were positive for the pulvinar sign in one. Other features were hyperintensity of the dorsomedial thalamic nuclei (93%), caudate head (40%), and periaqueductal gray matter (83%) on FLAIR images. CONCLUSION: In the appropriate clinical context, demonstration of the pulvinar sign on MR images is a highly accurate diagnostic sign for vCJD. FLAIR sequence is more sensitive than other sequences. Positive MR images may obviate more invasive diagnostic tests in most cases.     

U.S. military officer participation in the Centers for Disease Control and Prevention's Epidemic Intelligence Service (1951-2001)

The Epidemic Intelligence Service (EIS) was created in 1951 to provide epidemiologists to investigate natural and intentional disease epidemics. From an initial class of 23 U.S. citizens, the program has evolved into a globally recognized, hands-on learning experience, accepting approximately 65 to 75 new officers each year. The first U.S. military epidemic intelligence service officer (EISO) was accepted into the program in 1994. Since that time, 12 such officers have completed, or have begun, EIS training. They have comprised 2.1% of all EISOs from 1994 to 2001 and 0.47% of all EISOs. This total has included nine Air Force veterinarians, one Army veterinarian, one Army physician, and one Navy physician. Each military EISO had the opportunity to lead investigations of significant public health events (e.g., Ebola, monkeypox, malaria, Nipah virus, West Nile fever, and anthrax outbreaks). All graduates from the military returned to active duty assignments in operational medical units, research institutes, or the intelligence community.     

Clinical outcome of anterior cruciate ligament reconstruction with quadrupled hamstring tendon graft and bioabsorbable interference screw fixation

BACKGROUND: To date, there has been no publication of clinical follow-up data on patients who have undergone quadrupled hamstring tendon autograft anterior cruciate ligament reconstruction with bioabsorbable screw fixation. PURPOSE: To report the results of quadrupled hamstring tendon autograft anterior cruciate ligament reconstruction with bioabsorbable interference screw fixation. STUDY DESIGN: Retrospective review. METHODS: Sixty-five patients (66 knees) were retrospectively identified by chart review as having undergone quadrupled hamstring tendon autograft anterior cruciate ligament reconstruction with bioabsorbable interference screw fixation with a minimum 2-year follow-up. RESULTS: Data were collected on 48 knees in 47 patients (73%) at an average 30.2 months (range, 24 to 43) after surgery. Thirty-six patients (37 knees) returned for clinical evaluation (56% return) and subjective follow-up only was obtained in 11 patients (17%). The mean Lysolm knee score was 91 (range, 45 to 98), with a mean of 97 for the uninvolved knee. The mean Tegner activity score was 5.7 (range, 3 to 7). The KT-1000 arthrometer mean side-to-side difference for manual maximum displacement was 2.03 mm (range, -1 to 8). The mean International Knee Documentation Committee knee score was 83 (range, 47 to 100). Patients who underwent associated partial meniscectomy or meniscal repair had significantly lower International Knee Documentation Committee scores than patients without associated procedures (P < 0.01). CONCLUSIONS: Quadrupled hamstring tendon autograft anterior cruciate ligament reconstruction with bioabsorbable interference screw fixation is comparable with other methods of anterior cruciate ligament reconstruction in terms of patient satisfaction, knee stability, and function.     

In vivo evaluation of pretargeted 64Cu for tumor imaging and therapy.

Pretargeting involves administration of a tumor-targeting monoclonal antibody (mAb) covalently linked to a molecule having a high-affinity binding site for a rapidly distributed radiolabeled effector molecule. The aim of this study was to compare pretargeting to a conventionally labeled antibody for tumor targeting of the intermediate-lived radionuclide (64)Cu, which has shown promise for PET imaging and radioimmunotherapy of cancer. METHODS: DOTA-biotin (where DOTA is 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid) and the intact immunoconjugate DOTA-NR-LU-10 were labeled to high specific activities with (64)Cu, and the serum stabilities and target binding capabilities of each agent were assayed in vitro. Nude mice bearing SW1222 human colorectal carcinoma xenografts were administered (64)Cu-DOTA-biotin, with and without pretreatment with the mAb-streptavidin conjugate NR-LU-10/SA and the synthetic clearing agent Biotin-GalNAc(16), or injected with (64)Cu-DOTA-NR-LU-10. Biodistributions of both agents were obtained from 5 min to 48 h after injection. RESULTS: Both (64)Cu-DOTA-biotin and (64)Cu-DOTA-NR-LU-10 were 100% stable in serum in vitro. (64)Cu-DOTA-biotin exhibited >98% specific binding to immobilized streptavidin, whereas the immunoreactivity of (64)Cu-DOTA-NR-LU-10 averaged nearly 80%. Biodistributions in SW1222-bearing mice showed that NR-LU-10/SA-pretargeted (64)Cu-DOTA-biotin attained a peak tumor uptake of 18.9 percentage injected dose per gram (%ID/g) at 1 h, with concomitant rapid disappearance from blood and renal excretion. In the absence of pretargeting, (64)Cu-DOTA-biotin had very similar biodistribution and clearance properties, except with extremely low nonspecific tumor uptake. In contrast, (64)Cu-DOTA-NR-LU-10 reached 80.3 %ID/g in tumor tissue, after 48 h, whereas blood clearance was considerably slower than pretargeted (64)Cu-DOTA-biotin. Comparison of the time-activity curves for tumor uptake and blood clearance of pretargeted (64)Cu and the (64)Cu-labeled antibody revealed that the maximum tumor accumulations of radioactivity were similar for each agent, 17.9 percentage injected activity per gram (%IA/g) and 20.7 %IA/g, respectively. However, the tumor-to-blood ratio of areas under the curves was 14 times higher for pretargeted (64)Cu-DOTA-biotin because of the substantial increase in blood clearance of the small effector molecule. CONCLUSION: The extremely rapid tumor uptake and blood clearance of pretargeted (64)Cu-DOTA-biotin should afford markedly superior PET imaging contrast and therapeutic efficacy, compared with conventionally labeled (64)Cu-DOTA-NR-LU-10. Further comparison of the therapeutic efficacy, toxicity, and dosimetry of these 2 agents is warranted.     

Suspected early or mild chronic pancreatitis: enhancement patterns on gadolinium chelate dynamic MRI. Magnetic resonance imaging

PURPOSE: To assess whether measuring the pattern of pancreatic enhancement on gadolinium chelate dynamic magnetic resonance imaging (MRI) is helpful for diagnosis of suspected early or mild chronic pancreatitis. MATERIALS AND METHODS: In this retrospective study, 24 patients with suspected early or mild chronic pancreatitis, classified by imaging criteria of equivocal chronic pancreatitis (ultrasound, computed tomography [CT] or ERCP) grading, had dynamic MRI that included unenhanced, arterial dominant, early venous, and late venous phases of contrast enhancement. Twenty patients without pancreatic diseases also had the dynamic sequence as a control group. The signal intensity was measured at the pancreatic head, body, and tail on all phases, and for each, the signal intensity ratio (SIR, the signal intensity in postcontrast divided by that in precontrast) was calculated. Two radiologists independently reviewed the images of the patients with suspected early or mild chronic pancreatitis for pancreatic morphologic abnormalities without knowing the results of signal intensity measurements. RESULTS: On unenhanced images, there was no significant difference of signal intensity between control and pancreatitis groups (P < 0.05). In the pancreatitis group, but not in the control group, the unenhanced signal intensity of the pancreatic head and body were significantly higher than that of the tail (P < 0.05). In the control group, the greatest enhancement (highest SIR) after injection was in the arterial phase (1.89 +/- 0.31), significantly higher than that in the early venous phase (1.68 +/- 0.17, P < 0.01) and in the late venous phase (1.61 +/- 0.15, P < 0.001). The pancreatitis group, however, had an arterial phase SIR (1.65 +/- 0.23) that was significantly lower than its early venous phase SIR (1.75 +/- 0.22, P < 0.05) and lower than the arterial phase SIR of the control group (P < 0.01). The presence of an SIR less than 1.73 in the arterial phase and/or a delayed peak enhancement after contrast agent administration had a sensitivity and specificity of diagnosing early or mild chronic pancreatitis of 92% and 75%, respectively. This sensitivity was significantly higher than the sensitivity of 50% for diagnosis based on morphologic abnormalities (P < 0.05). CONCLUSION: Measuring pancreatic signal intensity on gadolinium chelate dynamic MRI is helpful for diagnosing early or mild chronic pancreatitis, especially before apparent pancreatic morphologic or signal intensity changes are present.