Arginine-vasopressin and the regulation of aggression in female Syrian hamsters (Mesocricetus auratus).

Arginine-vasopressin (AVP) is critical for the expression of a variety of social behaviors in many species. Previous studies have demonstrated that AVP regulates behaviors such as social communication and aggression in Syrian hamsters through the V1a receptor subtype. In male hamsters, AVP injected into the anterior hypothalamus (AH) stimulates aggression, while injection of a V1a receptor antagonist inhibits the behavior. The purpose of the present studies was to determine whether AVP influences aggression by its action in the AH in female hamsters. In the first experiment, we were surprised to find that injection of the V1a receptor antagonist, Manning compound, into the AH of intact female hamsters increased aggression. The second experiment confirmed the ability of the V1a receptor antagonist to increase aggression and found that the largest effects of the antagonist occurred at intermediate concentrations of the compound. The next experiment found that injection of AVP into the AH significantly reduced the latency to attack and the duration of aggression. Finally, we examined whether the effects of AVP and the V1a receptor antagonist on aggression differed in hamsters exposed to long 'summer-like' photoperiods or short 'winter-like' photoperiods, and found that their effects on aggression were not photoperiod dependent. In summary, contrary to what is observed in males, these data suggest that AVP in the AH may play an inhibitory role on aggression in female Syrian hamsters.

Biodistribution and dosimetry results from a phase III prospectively randomized controlled trial of Zevalin radioimmunotherapy for low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma.

UNLABELLED: Radiation dosimetry studies were performed in patients with non-Hodgkin's lymphoma (NHL) treated with 90Y Zevalin (90yttrium ibritumomab tiuxetan, IDEC-Y2B8) on a Phase III open-label prospectively randomized multicenter trial. The trial was designed to evaluate the efficacy and safety of 90Y Zevalin radioimmunotherapy compared to rituximab (Rituxan, MabThera) immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed NHL. An important secondary objective was to determine if radiation dosimetry prior to 90Y Zevalin administration is required for safe treatment in this patient population. METHODS: Patients randomized into the Zevalin arm were given a tracer dose of 5 mCi (185 MBq) (111)In Zevalin (111indium ibritumomab tiuxetan) on Day 0, evaluated with dosimetry, and then administered a therapeutic dose of 0.4 mCi/kg (15 MBq/kg) 90Y Zevalin on Day 7. Both Zevalin doses were preceded by an infusion of 250 mg/m(2) rituximab to clear peripheral B-cells and improve Zevalin biodistribution. Following administration of (111)In Zevalin, serial anterior and posterior whole-body scans were acquired and blood samples were obtained. Residence times for 90Y were estimated for major organs, and the MIRDOSE3 computer software program was used to calculate organ-specific and total body radiation absorbed dose. Patients randomized into the rituximab arm received a standard course of rituximab immunotherapy (375 mg/m(2) weekly x 4). RESULTS: In a prospectively defined 90 patient interim analysis, the overall response rate was 80% for Zevalin vs. 44% for rituximab. For all patients with Zevalin dosimetry data (N=72), radiation absorbed doses were estimated to be below the protocol-defined upper limits of 300 cGy to red marrow and 2000 cGy to normal organs. The median estimated radiation absorbed doses were 71 cGy to red marrow (range: 18-221 cGy), 216 cGy to lungs (94-457 cGy), 532 cGy to liver (range: 234-1856 cGy), 848 cGy to spleen (range: 76-1902 cGy), 15 cGy to kidneys (0.27-76 cGy) and 1484 cGy to tumor (range: 61-24274 cGy). Toxicity was primarily hematologic, transient, and reversible. The severity of hematologic nadir did not correlate with estimates of effective half-life (half-life) or residence time of 90Y in blood, or radiation absorbed dose to the red marrow or total body. CONCLUSION: 90Y Zevalin administered to NHL patients at non-myeloablative maximum tolerated doses delivers acceptable radiation absorbed doses to uninvolved organs. Lack of correlation between dosimetric or pharmacokinetic parameters and the severity of hematologic nadir suggest that hematologic toxicity is more dependent on bone marrow reserve in this heavily pre-treated population. Based on these findings, it is safe to administer 90Y Zevalin in this defined patient population without pre-treatment (111)In-based radiation dosimetry.

Dual-isotope motion correction technique for gated exercise scintigraphy.

In exercise multigated blood-pool imaging, significant degradation of image quality occurs as a result of patient movement under the gamma camera. Motion correction devices using centroid tracking of x-y events emanating from the organ of interest cannot be applied to blood-pool studies, because cardiac contraction and rotation masks the correctable patient motion component. We have developed a dual-isotope motion correction technique (DIMC) which utilizes a second point source of dissimilar energy (241Am) to monitor movement. Positional centroids from events incident in the 241Am window are used to develop correction coordinates which are applied to the 99mTc blood-pool events. The ability of DIMC to reduce blur due to motion has been evaluated qualitatively with phantoms and quantitatively by using spatial resolution measurements obtained from stationary line sources and from sources moving at varying rates. Based on these criteria, we have found the device to be capable of reducing over 90% of the image blur of objects moving at 5.1 cm per sec. In preliminary gated exercise studies, subjective perception of image quality was shown to be significantly improved in the DIMC corrected image, when compared to images obtained without DIMC. Improvement in image quality for exercise gated studies is of particular importance because of the low count density obtained during these procedures.

Multigated blood-pool imaging using heart sounds.

A method to trigger multigated blood-pool (MGBP) acquisition using both the first and second heart sound has been developed. The heart sound gating (HSG) circuitry identifies, individually, both the first (S1) and second (S2) heart sounds from their timing relationship alone, and provides two trigger points during the cardiac cycle. First heart sound gating may be performed to assess the systolic ejection portion of the cardiac cycle, with S2 gating utilized for reproduction of the diastolic filling portion of the cycle. Heart sound gating has been applied to twenty patients who underwent analysis of left ventricular function, and compared to conventional ECG-gated MGBP. Left ventricular ejection fractions calculated from MGBP studies using a first and a second heart sound trigger correlated well with conventional ECG gated acquisitions in patients adequately gated by HSG and ECG. Heart sound gating may be utilized in patients with rapidly changing heart rates, as S1 and S2 precisely define end-diastole and end-systole, respectively, and in situations when the ECG is inadequate for gating purposes.

Planar imaging versus gated blood-pool SPECT for the assessment of ventricular performance: a multicenter study.

UNLABELLED: Gated blood-pool SPECT (GBPS), inherently 3-dimensional (3D), has the potential to replace planar equilibrium radionuclide angiography (ERNA) for computation of left ventricular ejection fraction (LVEF), analysis of regional wall motion (RWM), and analysis of right heart function. The purpose of this study was to compare GBPS and ERNA for the assessment of ventricular function in a large, multicenter cohort of patients. METHODS: One hundred seventy-eight patients referred in the usual manner for nuclear medicine studies underwent ERNA followed by GBPS. Each clinical site followed a GBPS acquisition protocol that included 180 degrees rotation, a 64 by 64 matrix, and 64 or 32 views using single- or double-head cameras. Transverse GBPS images were reconstructed with a Butterworth filter (cutoff frequency, 0.45-0.55 Nyquist; order, 7), and short-axis images were created. All GBPS studies were processed with a new GBPS program, and LVEF was computed from the isolated left ventricular chamber and compared with standard ERNA LVEF. Reproducibility of GBPS LVEF was evaluated, and right ventricular ejection fraction (RVEF) was computed in a subset of patients (n = 33). Using GBPS, RWM and image quality from 3D surface-shaded and volume-rendered cine displays were evaluated qualitatively in a subset of patients (n = 30). RESULTS: The correlation between GBPS LVEF and planar LVEF was excellent (r = 0.92). Mean LVEF was 62.2% for GBPS and 54.1% for ERNA. The line of linear regression was GBPS LVEF = (1.04 x ERNA LVEF) + 6.1. Bland-Altman plotting revealed an increasing bias in GBPS LVEF with increasing LVEF (Y = 0.13x + 0.61; r = 0.30; mean difference = 8.1% +/- 7.0%). Interoperator reproducibility of GBPS LVEF was good (r = 0.92). RVEF values averaged 59.8%. RWM assessment using 3D cine display was enhanced in 27% of the studies, equivalent in 67%, and inferior in 7%. CONCLUSION: GBPS LVEF was reproducible and correlated well with planar ERNA. GBPS LVEF values were somewhat higher than planar ERNA, likely because of the exclusion of the left atrium.

Prediction of radiation doses from therapy using tracer studies with iodine-131-labeled antibodies.

UNLABELLED: Tracer pharmacokinetic studies are often used in treatment planning for radionuclide therapy including radioimmunotherapy. This study evaluates the validity of using tracer studies to predict radiation doses from therapy with the same radiolabeled antibody. METHODS: Quantitative imaging and blood radioactivity were used to obtain the pharmacokinetics and radiation doses that were delivered to the total body, blood, marrow, lungs, liver, kidneys, thyroid, spleen and tumors. Tracer and therapy data for eight patients with lymphoma and one patient with breast cancer were compared using linear regression statistics. Doses of 131I-labeled antibody for the tracer studies ranged from 0.1 to 0.4 GBq (2 to 10 mCi), and therapy doses ranged from 0.7 to 5.6 GBq (20 to 150 mCi). RESULTS: Radiation doses to tissues and, in particular, the bone marrow and tumors were reliably predicted from tracer studies. In this group of patients, median dose to marrow from marrow targeting, total body and blood was 9.2 cGy/GBq for tracer studies and 7.6 cGy/GBq for therapy studies with a median difference of 0.5 cGy/GBq. Median dose to tumors was 81.1 cGy/GBq for tracer studies and 70.3 cGy/GBq for therapy studies with a median difference of 5.9 cGy/GBq. CONCLUSION: In these patients, tracer studies were predictive of the radiation doses from therapy for total body, major organs and tumors. The radiation doses to marrow and tumors, which are the usual determinants of the therapeutic index, correlated well between tracer and therapy studies (r > or = 0.95).

A radioimmunoimaging and MIRD dosimetry treatment planning program for radioimmunotherapy.

A treatment planning program for radioimmunotherapy employing quantitative Anger camera imaging and the MIRD formalism has been designed and implemented on a clinical nuclear medicine computer. Radionuclide residence times are calculated from linear, mono- and bi-exponential, and cubic spline fits to regional activity versus time curves, and radiation-absorbed dose estimates for all target organs for 131I, 67Cu, and 58 other radionuclides can be calculated. This software has been successfully applied to radioimmunotherapy of B-cell malignancies and breast adenocarcinomas.

Harrington instrumentation and arthrodesis for idiopathic scoliosis. A twenty-one-year follow-up.

A questionnaire was sent to 206 consecutive patients who were operated on for idiopathic scoliosis by Dr. Paul R. Harrington between 1961 and 1963. Eighty-three per cent of the patients responded to the questionnaire, which consisted of five sections: demographic data, activities of daily living, back symptoms (pain and fatigue), a history of personal and family health, and a personal assessment of the back. One hundred and eleven patients also sent recent radiographs. A control group, comprising 100 individuals who did not have scoliosis and had been matched for age and sex, was given the same questionnaire. The study group had more pain in the interscapular and thoracolumbar regions compared with the control group, but there was no difference with respect to pain in the lumbosacral area or the low back. Neither pain nor fatigue was related to the type of curve, the preoperative degree of curvature, the degree of curvature as seen on the most recent radiograph, the extent of fusion into the lumbar spine, or the presence of a broken rod. Twenty-one years after the operation, the patients were functioning quite well compared with the control subjects.

The postoperative management of scoliosis patients treated with Harrington instrumentation and fusion.

A retrospective study of maintenance of correction as affected by modifications in the management of patients surgically treated for scoliosis showed better results in Group B than in Group A. No supplementary bone was used in the 187 patients in Group A, who were maintained recumbent for three months postoperatively and who wore an underarm body cast for six months. The 177 patients in Group B received autogenous iliac-bone grafts, were allowed to walk seven to ten days postoperatively, and wore an underarm body cast for nine months. By two years postoperatively the patients in Group A had lost an average of 8.3 degrees of correction, and the patients in Group B had lost 4.3 degrees. A pseudarthrosis developed in eight patients in Group A and in one patient in Group B.

Results of reduction and stabilization of the severely fractured thoracic and lumbar spine.

From 1962 to 1976, ninety-five patients with fracture-dislocations of the spine were treated with Harrington instrumentation and fusion within ninety days of injury. This report presents the results of this procedure related to reduction, stabilization, return of neural function, and total hospital stay. Mean follow-up was twenty-one months. Reduction and stabilization were attained without a substantial number of complications, but no more return of neural function in the patients was evident than has been reported in the literature for patients treated with postural reduction and bed rest. Total hospital stay averaged 107 days from day of injury.

Clinical review of patients with broken Harrington rods.

The medical records and roentgenograms of 2,016 patients who were operated on from 1961 through 1974 using Harrington spinal instrumentation were reviewed to determine the incidence, clinical significance, and management of broken distraction and compression rods. The cases were divided into two study groups. Group A includes 1,128 patients operated on from 1961 through 1968, when no autogenous iliac-bone graft material was used, and Group B includes 888 patients operated on from 1969 through 1974, when autogenous bone was used. The incidence of broken distraction rods was 12.5 per cent (141 patients) in Group A and 2.1 per cent (nineteen patients) in Group B. The age of the patient at operation was not found to be a significant factor when comparing patients with fractured rods and those with intact rods; however, preoperative curve magnitude was found to influence the incidence of rod fractures. Reinstrumentation of distraction rods was required in twenty-three patients from Group A, but no patients in Group B required reinstrumentation. Eleven patients from Group A required removal of the rods. The compression rod fractured in forty patients (3.5 per cent) in Group A and in one patient in Group B; none required reinstrumentation or rod removal. The clinical management of rod fractures must be individualized for each patient. Reinstrumentation and fusion may be indicated in patients with early rod fracture, total loss of correction, or overlapping of the rod, but not in patients experiencing little or no loss of correction and no associated symptoms.

Results of operative treatment of idiopathic scoliosis in adults.

We compared the results in eighty-one patients (average age, fifty-six years; range, forty-three to eighty-three years) who had had operative treatment of idiopathic scoliosis with those in thirty patients (average age, fifty-eight years; range, forty-five to seventy years) who had declined operative treatment. Seventy-six individuals (average age, forty-eight years; range, thirty-five to seventy-four years) who did not have scoliosis served as a control group. The average duration of follow-up was five years (range, two to seventeen years). The population base consisted of 454 patients who were seen between 1970 and 1985. The treated patients were drawn from a group of 160 patients for whom an operation had been recommended; 110 patients agreed to the operation and fifty refused. The remaining 294 patients had curves of insufficient severity to warrant concern about progression, had symptoms unrelated to the scoliosis, or had curves that did not necessitate any intervention. The functional status since the operation (for the treated patients), since recommendation of the operation (for the untreated patients), or within the last ten years (for the control group) was evaluated with a comprehensive questionnaire designed to elicit details regarding pain, fatigue, and any disability in the performance of twenty-six activities of daily living. At the most recent follow-up examination, the treated patients reported a significantly greater decrease in pain and fatigue and significantly more improvement in self-image and in the ability to perform physical, functional, and positional tasks than did the untreated patients (p = 0.0001).

Results of Harrington instrumentation and fusion in the adult idiopathic scoliosis patient.

Between January 1961 and December 1972, 132 patients over twenty years old with idiopathic scoliosis were surgically treated using Harrington instrumentation and fusion techniques. All patients were seen by us because of curve magnitude or symptoms secondary to scoliosis. The average correction obtained at operation was 48 per cent. Twenty-four patients had early complications. Fifty-two had late complications, the most frequent of which was pseudarthrosis. The majority of patients had significant improvement in symptoms as a result of surgical correction and stabilization.

An MRI tissue equivalent lesion phantom using a novel polysaccharide material.

A new polysaccharide material, TX-150, and method is described which will potentially allow formation of stable, multi-compartment MRI phantoms constructed without intervening septa. TX-150 can be made into water based gels which are nominally tissue equivalent. Although contiguous regions of different water content are not possible, as water diffusion will occur until equilibrium is reached, TX-150 gel T1 and T2 values can be adjusted independently, while maintaining a constant water composition, by appropriate additives. Unlike paramagnetic ions and chelates, metal phthalocyanines have been found to bind tightly to TX-150, thus, permitting formation of stable contiguous regions of differing T1 relaxation properties. Phantom T2 values can be effectively modified with 2-2-diphenyl-1 picrylhydrazyl, which has little affect on gel T1 values, to form septumless lesion phantoms of varying T1 and T2.

A new heart-sounds gating device for medical imaging.

A heart-sounds gating device has been designed and tested which identifies, individually, both the first (S1) and second (S2) heart sound from their timing relationship, providing two trigger points through the cardiac cycle for synchronizing medical images. The new heart-sounds gate utilizes dynamically varying timing windows to anticipate the occurrence of S1 and S2. The heart-sounds gate has been initially applied to nuclear imaging of the cardiac bloodpool, but may be applied to any imaging modality requiring cardiac synchronization.

Quantitative radioimmunoimaging for radioimmunotherapy treatment planning: effect of reduction in data sampling on dosimetric estimates.

Quantitative radioimmunoimaging (serial anterior/posterior imaging and blood sampling) is useful for radioimmunotherapy treatment planning, but can be quite time consuming. To predict whether accurate radiation absorbed dose estimates can be maintained with a reduction in data sampling, 12 patients undergoing indium-111/yttrium-90 anti-CD20 monoclonal therapy for whom absorbed doses were estimated based on eight data samples (acquired at 0, 2, 4, 24, 48, 72, 96, and 144 h, respectively), were retrospectively reanalyzed using only five samples (0, 4, 24, 72, and 144 h, respectively). Calculated residence times (in h) and absorbed doses (in cGy), for the whole body, kidneys, liver, lungs, spleen, and red marrow were compared with the original values based on the eight samples using Student's paired t-test. Linear regression and Bland-Altman analysis of the two data sample groups was also performed. The mean residence times in the five- and eight-data samples groups were essentially the same (17.7 +/- 26.6 h [range, 0.3-79.0 h] versus 17.6 +/- 26.6 h [range, 0.3-79.5 h]; p = 0.72), as were the mean absorbed doses (336 +/- 411 cGy [range, 38-2434 cGy] versus 325 +/- 381 cGy [range, 39-2246 cGy]; p = 0.24). Also, the linear regressions were excellent (residence time y = 1.00x + 0.09 h [r = 0.99]; absorbed dose y = 1.06x - 7.74 cGy [r = 0.98]). Additionally, Bland-Altman analysis revealed no significant sample bias in residence time (0.03 +/- 0.68 h, 0.9% +/- 10.0) or absorbed dose (11 +/- 76 cGy, 1.0% +/- 9.3). These results demonstrate that reduced data sampling in quantitative radioimmunoimaging can be achieved without significantly altering radiation absorbed dose estimates, but with a significant savings in imaging, blood sampling, and processing time.

Efficacy and cost considerations of intraoperative autologous transfusion in spinal fusion for idiopathic scoliosis with predeposited blood.

STUDY DESIGN: One hundred five patients with adolescent idiopathic scoliosis who underwent posterior spinal instrumentation and fusion with predeposited autologous blood, with or without intraoperative autologous transfusion, were reviewed. OBJECTIVE: To determine the benefit/nonbenefit of intraoperative autologous transfusion in diminishing the need for homologous blood and influencing post-operative hematocrit values in healthy adolescents undergoing spinal fusion for scoliosis. SUMMARY OF BACKGROUND DATA: A steady increase in the use of intraoperative autologous transfusion in recent years has occurred without guidelines regarding which procedures and patient populations would be best served. Previous studies have failed to determine the cost effectiveness and actual reduction in homologous blood exposure attributable to intraoperative autologous transfusion in adolescents who have undergone preoperative phlebotomy. METHODS: Fifty-five adolescents (intraoperative autologous transfusion group) who underwent posterior instrumentation and fusion for idiopathic scoliosis with the use of an intraoperative autologous transfusion device were compared to 50 patients (control group) who underwent the same procedure without the intraoperative autologous transfusion device. RESULTS: The average percent salvage of red blood cells by the intraoperative autologous transfusion device was 35%. The control group utilized significantly more of the predonated autologous blood than the intraoperative autologous transfusion group (1.34 units/case vs. 1.78 units/case, P < 0.05). Homologous blood usage was the same in both groups. Two patients in the intraoperative autologous transfusion group required nondirected homologous blood (total of four units), compared to three patients in the control group (total of four units) (P = 0.048). Using multiple regression analysis, the total number of transfusions was significantly correlated with the estimated blood loss and the duration of surgery in both groups. Postoperative hematocrit levels were slightly higher in the control group, but there was not a significant difference. CONCLUSIONS: The addition of intraoperative autologous transfusion to a preoperative phlebotomy program had no benefit on homologous blood exposure or post-operative hematocrit changes in this population. Blood requirements for this procedure can be met less expensively and more reliably by merely donating one's own blood.

Lumbar spine duplication presenting as adolescent scoliosis. A case report.

STUDY DESIGN: A report of a case of lumbar spine duplication with the clinical appearance of adolescent scoliosis. OBJECTIVE: To increase knowledge about the pathogenesis and treatment of lumbar spinal duplication. SUMMARY OF BACKGROUND DATA: Although there have been other reports of lumbar spine duplication of this magnitude, these malformations typically are associated with severe neurologic abnormalities (dicephalus, myelomeningocele) or gastrointestinal abnormalities (omphalocele, neurenteric fistulas). Several investigators have recommended early surgical intervention for this abnormality because of the perceived risk of progressive neurologic abnormality from tethering of the cord. METHODS: In a 13-year-old girl who had truncal asymmetry, lumbar spine duplication was noted on plain radiographs. A magnetic resonance study was obtained, and the patient was observed with conservative treatment for 3 years. RESULTS: Although extensive abnormalities were noted on the magnetic resonance images, which were related to duplication of spinal cord and vertebral bodies, the patient was neurologically intact and remained so until skeletal maturity. CONCLUSIONS: This rare malformation typically has severe neurologic sequelae. Conservative management in the reported patient did not result in a progressive neurologic lesion at the time of skeletal maturity.

Hypotensive anesthesia for scoliosis surgery in Jehovah's Witnesses.

Hypotensive anesthesia has been advocated in spinal surgery for the purpose of diminishing operative blood loss. This study evaluated its effectiveness in 12 Jehovah's Witnesses undergoing Harrington instrumentation and fusion who refused transfusion. Previous series from this institute did not use deliberate hypotension because of routinely low blood loss. Compared with matched controls operated on under normotensive anesthesia, the Jehovah's Witness patients had lower absolute blood loss but also shorter operative time. Applied linear-regression analysis demonstrated that the diminished blood loss was associated with shorter operative time (P = 0.0002) rather than lower blood pressure. The majority of blood losses in spinal instrumentation with fusion occurs with decortication. This rapid bleeding occurs at venous pressures which are unaffected by arterial blood pressure manipulation. The authors conclude that spinal surgery is possible in Jehovah's Witnesses without transfusion and that operative technique is the single most important determinant of blood loss.

Body and blood clearance and marrow radiation dose of 131I-Lym-1 in patients with B-cell malignancies.

Fifty-eight per cent of patients with B-cell malignancies had durable responses to treatment with 131I-Lym-1. Myelosuppression manifested by peripheral blood cytopenia was the radiation dose-limiting toxicity. The mean biologic half-times were 3.3 and 31.2 h for the fast and slow phases, respectively, of the blood clearance and 33.5 h for the clearance from the total body. Nonpenetrating radiation from the blood contributed 0.18 rad and penetrating radiations from the total body contributed 0.18 rad per administered mCi to the bone marrow. The average total contribution from both of these sources was 0.36 +/- 0.14 rad mCi-1. Clearances and marrow radiation doses were remarkably constant among different patients and among different therapy doses for the same patient. These results are potentially useful as an initial approximation for other mouse monoclonal antibodies of the same isotype. While radiation to normal marrow from 'spill-over' incident to specific targeting of 131I-Lym-1 on malignant B-cells in the marrow is not addressed in this publication because it is unique for each patient, it should be considered in the case of individual patients.