Diagnosis of coronary artery disease based on blood pool radioisotope angiography at rest.

BACKGROUND: The author wanted to determine which of 3 parameters (global left ventricular ejection, regional left ventricular ejection fraction, or isocontours together with peak filling rate and time of peak filling rate) measured with blood pool radioisotope angiography at rest was sufficient to permit diagnosis of coronary artery disease. METHODS: Thirty-one patients with coronary artery disease and 11 hypertensive patients without coronary heart disease were assessed with blood pool radioisotope angiography using a computerized large-field gamma camera. RESULTS: Of the 3 parameters measured, only assessment of isocontours with peak filling rate and time of peak filling rate provided sufficient information for establishing a diagnosis of coronary artery disease. In contrast, measurement of global left ventricular ejection provided equivocal data, as did that of regional left ventricular ejection fraction. CONCLUSIONS: In combination with peak filling rate and time of peak filling rate, measurement of isocontours by blood pool radioisotope angiography at rest provided sufficient information for establishing a diagnosis of coronary artery disease.

Evaluation of heart dysfunction using non-invasive methods. A comparison between left ventricular end diastolic volume measured using blood pool gated radioisotope angiography and left ventricular transverse end diastolic diameter measured using two dimensional echocardiography.

BACKGROUND: The author aimed to compare two heart function indexes by studying left ventricular end diastolic volume measured using blood pool gated radioisotope angiography, and left ventricular end diastolic diameter measured using echocardiography. METHODS: The patients were divided into two groups depending on whether left ventricular ejection fraction was greater than or equal to 50% or less than 50%, namely into a group of patients without myocardial dysfunction and one with myocardial dysfunction. The results were analysed using Fisher's discriminant analysis. RESULTS: The author observed that 41.18% of patients were correctly classified using the end diastolic volume and 82.35% using transverse end diastolic diameter. Student's "t"-test was also performed on end diastolic volumes in the first and second group, although this was not significant. On the contrary, the "t" test between the transverse end diastolic diameters of patients in the first and second group was significant with p < 0.05. CONCLUSIONS: The author concludes that the end diastolic transverse diameter of the left ventricle is a reliable index of myocardial dysfunction.

Allogeneic transplantation of unmanipulated peripheral blood stem cells in patients with multiple myeloma.

In multiple myeloma (MM), allogeneic bone marrow transplantation may produce complete and durable responses, but is accompanied by significant transplant-related mortality (TRM). To assess feasibility and possible advantages offered by the use of allogeneic, growth factor-primed PBSC instead of marrow, we analyzed the data of 10 patients with MM (IgG = 6, IgA = 1, BJ = 2, non-secreting = 1; stage II = 1, stage III = 8, plasma-cell leukemia = 1) who received an allogeneic transplant with PBSC. Their age ranged between 35 and 53 years (median 45). All were HLA-identical to their sibling donors. Prior to allograft, six patients received standard-dose chemotherapy (DAV or CY-Dexa) and four a sequential intensified scheme with autologous PBSC support. At the time of transplantation, three patients were in CR, three in PR, three had refractory disease, one progressive disease. Patients were conditioned with busulfan-melphalan (n = 9) or busulfan-cyclophosphamide (n = 1), and were allografted with unmanipulated PBSC obtained by apheresis after treatment with G-CSF alone (n = 6) or GM-CSF followed by G-CSF (n = 4). All patients engrafted, with 0.5 x 10(9)/l PMN and 50 x 10(9)/l platelets on (median) day 13. Four patients had > or =grade II acute GVHD (grade II in 3, grade III in 1). Following allograft, CR was achieved in 71% patients. Eight are currently alive, with six in CR at a median of 18.5 months (range 7-28) from the transplant. Two patients died, 1 and 4 months from the allograft, respectively, and one is alive with progression. A PCR analysis of IgH rearrangement showed that residual disease was no more molecularly detectable in four out of seven evaluated patients following allograft. The results suggest that PBSC may improve the therapeutic efficacy of allogeneic transplant in MM, not only by a reduction of TRM but also by an improvement of rate and quality of response.

PBSC mobilization, collection and positive selection in patients with chronic lymphocytic leukemia.

We report the results of PBSC mobilization and immune selection in 17 patients with advanced chronic lymphocytic leukemia (CLL) enrolled in a multicenter Italian study of autologous transplantation with peripheral CD34+ selected cells. Mobilization was achieved by cyclophosphamide (CY) 4 g/m2 + G-CSF 5 microg/kg. CD34+ cells were positively selected by means of avidin-biotin immunoaffinity columns (Ceprate SC) or immunomagnetic beads (Isolex 300i) systems. Evaluation of minimal residual disease was performed by PCR analysis of the IgH gene rearrangment on the apheresis product before and after selection. Our results showed that after CY a median of 3.6 x 10(6)/kg (0.5-12.8) CD34+ cells were collected with a median of two aphereses in 14 out of 17 patients; three failed to mobilize a number of CD34+ cells adequate for subsequent manipulation. We found that in CR patients CD34+ cell yield per apheresis was significantly higher than in PR patients (P < 0.05). Sixteen selection procedures were performed in 13 patients. CD34+ cell recovery was 33.5% (10-85) with a median final yield of 1 x 10(6)/kg CD34+. Two patients underwent marrow collection due to the low number of CD34+ cells recovered. Final purity was 59% (range 22-94) and CD5/20+ cell depletion was 2.7 log (1.6-4.4). Our data showed a statistically higher CD34+ cell recovery and purity with the Isolex device compared to Ceprate (P < 0.01 and 0.01, respectively). All the evaluable samples remained PCR positive after selection. The main issues to be addressed in the future are the identification of patients who fail mobilization and the improvement of purging methods.

[Single photon emission computed tomography in focal liver lesions]. / La tomografia da emissione di fotone singolo nelle lesioni focali epatiche.

BACKGROUND: Sixteen parameters of liver diseases including echography, liver scintigraphy with radioactive colloids, slices of the SPECT and the 3 dimensions surface display of the SPECT, were examined in 17 patients with liver disease. METHODS: The findings of imaging examinations were classified with a code of letters and numbers and patients with the same code were given the same number. The measured values were submitted to a multivariate analysis to evaluate which variable were significant to predict focal liver lesions. RESULTS: The slices of SPECT, TGP and bilirubin were the most significant indexes of liver lesions. CONCLUSIONS: The validity of SPECT in the study of focal liver lesions is confirmed.

Mobilization and collection of PBSC in healthy donors: a retrospective analysis of the Italian Bone Marrow Transplantation Group (GITMO).

BACKGROUND AND OBJECTIVE: The number of allogeneic transplants of peripheral blood stem cells (PBSC) is rapidly increasing. Collection of PBSC in healthy subjects currently implies the administration of G-CSF or GM-CSF and, of course, the use of apheretic devices. These procedures involve potential risks, in particular the risk of leukemia secondary to growth-factor treatment. To evaluate the current practice of PBSC mobilization and collection, and initially assess the short-term side effects and efficiency of procedures, the GITMO (Gruppo Italiano Trapianti di Midollo Osseo) promoted a retrospective cooperative study among the Italian centers. METHODS: Seventy-six healthy individuals donating to their HLA-identical or partially matched sibling recipients in seven Italian centers form the basis of the present analysis. The data were retrospectively collected by proper forms, pooled and analyzed by means of a commercially available statistical soft package. RESULTS: All donors received G-CSF as mobilizing agent with different schedules according to each single center policy. A median of 2.5 (range 1-4) aphereses per donor were run. The most frequent side effect was bone pain. In no case did the medium term follow-up reveal subjective complaints or laboratory modifications. After G-CSF mobilization, WBC and lymphocytes counts increased to a maximum of (mean +/- SD) 48.1 +/- 15.6 x 10(9)/L and 4.2 +/- 1.5 x 10(9)/L, respectively. The peak was reached on day 5 in both cases. Platelets decreased after the apheretic procedures, reaching a minimum of (mean +/- SD) 77 +/- 26 x 10(9)/L on day 8 and returning to normal values on day 11. Overall, the apheretic collection yielded (mean +/- SD) 18.6 +/- 19.2 x 10(8)/kg donor body weight MNC; 10.4 +/- 5.7 x 10(6)/kg CD34+ cells; 90.6 +/- 75.9 x 10(4)/kg CFU-GM and 4.3 +/- 1.8 x 10(8)/kg CD3+ cells. The target dose of 4 x 10(6)/kg CD34+ cells was harvested in 51.3% donors after a single apheresis, in 85.5% after the second, and in nearly 100% after a maximum of 3 aphereses. INTERPRETATION AND CONCLUSIONS: These data demonstrate that collection of adequate numbers of circulating progenitors is feasible and well tolerated in healthy donors. However, only careful monitoring of donors and international cooperation will help to definitively assess the long-term safety of G-CSF for mobilization of PBSC.

[Relationship between left ventricular dysfunction studied by multigated radionuclide angiography and carotid stenosis examined by Doppler]. / Relazione tra le dissinergie del ventricolo sinistro investigate con l'angiocardiografia radioisotopica all'equilibrio e le stenosi carotidee evidenziate con l'esame Doppler.

The multigated radio nuclide angiography was executed in 55 patients that were investigated for coronary heart disease and the left ventricular contour was determined in left anterior oblique view. The left ventricular contour was divided in 5 sectors and the isocontours (percentage of excursion between the systole and the diastole) and the regional ejection fractions were determined. The continuous wave Doppler test of the carotids was executed in the same patients. The patients were divided in 3 groups according to Doppler test: the group 1 owned the patients with the normal test (35 patients); the group 2 owned the patient with the moderately diseased test (14 patients); the group 3 owned the patients with frankly diseased test (6 patients). The following statistical analysis was executed: the 5 values of the isocontours and the 5 values of the ejection fractions were used to classify the patients in the 3 groups by mean of a discriminant analysis according to Fisher and the group for the highest conditional probability was considered for every patient. The analysis fixed that the 5 + 5 values of each patient classified correctly the 67.27 of the cases. If the only the values of the isocontours or of the ejection fractions or of the septum or of the ventricular lateral wall were used, the cases correctly classified were fewer. This paper contributes to the study of the relationship between the heart disease and the brain vessel disease and allows to regard the atherosclerosis a unique disease.

Transplantation of unmanipulated allogeneic PBSC: preliminary report on 24 patients.

To explore the feasibility and potential advantages of PBSC in allogeneic transplantation, we grafted 24 patients (age 16-57, median 37) with different hematologic diseases (ALL = 10, AML = 5, MM = 4, NHL = 2, CML = 1, MDS = 1, AA = 1), 23 HLA-identical to their siblings and 1 partially matched. Cells were collected from donors by apheresis after G-CSF 10 to 16 mg/kg/day for 4 to 5 days, and stored at 4 degrees C until infusion. The patients were conditioned with chemotherapy regimens including busulfan and cyclophosphamide in the majority of cases and received GVHD prophylaxis with CSA-MTX in all but two. The graft consisted of PBSC alone, with a median of 143.5 (range 18.1-358.9) x 10(4)/kg CFU-GM, 9.0 (range 3.3-18.0) x 10(6)/kg CD34+ cells and 2.8 (range 1.2 to 8.6) x 10(8)/kg CD3+ and cells. An ANC >0.0.5 x 10(9)/L was recovered on (median) day 13 (range 11-17), and a platelet count >50 x 10(9)/L on (median) day 13 (range 12-55) post graft. There was no correlation between CD34+ cells or CFU-GM number in the inoculum and time to hematologic reconstitution. Acute GVHD (grade II-IV) occurred in 10 out of 22 (45%), chronic GVHD in 10 out of 18 evaluable (55%) patients. We found no relationship between occurrence of acute or chronic GVHD and number of CD3+ cells in the graft. Four patients relapsed and 7 died after transplantation. Fifteen patients are currently alive and disease-free 67 to 710 (median 286) days from the graft. Allogeneic transplantation with unmanipulated PBSC ensures a fast and stable engraftment. Acute GVHD incidence and severity seems comparable to that of bone marrow transplantation, but there may be an increase in chronic GVHD, mainly of the extensive form.

[Diagnostic possibilities of left ventricular systolic-diastolic volume curve computed in patients with vascular diseases by means of multigated radionuclide angiocardiography]. / Possibilità diagnostiche della curva di volume sisto-diastolica del ventricolo sinistro computata in pazienti vasculopatici per mezzo dell'angiocardiografia radioisotopica all'equilibrio.

MATERIALS AND METHODS: In this study the multigated radionuclide angiography was performed in 54 patients with and without vascular diseases; the humeral arterial pressure was measured and the BMI was calculated in each patient by mean of the weight and height. The curve expressing the variations of the sisto diastolic volume of the left ventricle was generated from an analysis of the radioisotopic angiocardiography, and the curve, the BMI and the arterial pressure were used to calculate 14 different numeric values for each patient consisting of hemodynamic parameters of the left ventricular function. The diagnosis for each patient was then examined a posteriori and the patients were divided in 15 groups of which 1 with non-cardiovascular pathologies and 14 with cardiovascular pathologies alone or in association. A statistical analysis was performed to ascertain whether the parameters could be used to classify patients into the diagnostic groups using the Fisher's discriminant analysis. RESULTS: The obtained classification agreed in the 63% of the cases. CONCLUSIONS: This paper proved the possibility offered by the curve expressing the changes in the sisto diastolic volume of the left ventricle to discriminate between the various cardiovascular pathologies.

Mobilization and collection of PBSC in healthy donors: comparison between two schemes of rhG-CSF administration.

Procurement of a high number of progenitor cells is of primary interest in allogeneic PBSC transplantation. We have retrospectively compared toxicity, mobilization effect and progenitor cell yields of two different rhG-CSF schedules in 11 consecutive healthy individuals donating their PBSC. Five of them received rhG-CSF 16 micrograms/kg/d for 4 subsequent d in 2 divided subcutaneous injections (group A); similarly, 6 donors received rhG-CSF 10 micrograms/kg/d for 5 d (group B). The aphereses were started the last day of rhG-CSF treatment; 9 donors underwent 2 aphereses, one underwent 1 and another 3 procedures, always on subsequent days. Toxicity was mild, but moderate thrombocytopenia developed following apheretic collections, irrespective of rhG-CSF schedule. In all the donors WBC, as well as circulating CD34+ cells, CFU-GM, CFU-GEMM and BFU-E dramatically increased over the baseline values, peaking on d 5 or 6, with no statistical difference between the 2 groups for the height of the cell peaks. Also the peripheral lymphoid cell populations (CD3+, CD19+ and CD56+/CD3-) increased following the rhG-CSF administration. The number of MNC, CFU-GM, BFU-E, CFU-GEMM, as well as CD34+, CD3+, CD19+ and CD56+/CD3- cells collected by apheresis showed no statistical difference in the 2 groups. Overall, 8 of the 11 donors collected the target number of CD34+ cells > 4 x 10(6)/kg ideal recipient body weight with the first apheresis, with no difference between the 2 groups. Mobilization with rhG-CSF in healthy donors enables the collection of large number of progenitor cells with modest side effects. A schedule of 10 micrograms/kg for 5 d is as effective as 16 micrograms/kg for 4 d. A single apheresis would be enough in 80% of cases.

High incidence of chronic GVHD after primary allogeneic peripheral blood stem cell transplantation in patients with hematologic malignancies.

To assess feasibility and potential advantages of PBSC allograft, we transplanted nine patients (age 20-47 years) with advanced or poor-risk hematologic malignancies. These included eight HLA-identical sibling transplants and one partially matched. Cells were collected from donors by apheresis after rh-G-CSF 10-16 micrograms/kg/day for 4-5 days, and stored at 4 degrees C until infusion. Patients were conditioned with busulfan 16 mg/kg and cyclophosphamide 200 mg/kg, and received GVHD prophylaxis with CSA-MTX. The graft consisted of PBSC alone, with a median of 101.2 (range 28-254.2) x 10(4)/kg CFU-GM, 6.84 (range 4.57-15.9) x 10(6)/kg CD34+ cells and 2.5 (range 1.2-6) x 10(8)/kg CD3+ cells. An ANC > 0.5 x 10(9)/1 occurred on (median) day 13 range 11-17), and a platelet count > 50 x 10(9)/l on (median) day 15 (range 12-29) post graft. One patient died of ARDS on day 13, the others are alive 96-485 (median 245) days from the graft. Two patients have relapsed, one of them with isolated CNS involvement. Acute GVHD (grade I-II) occurred in three patients and severe chronic GVHD in six patients, with no relationship to CSA withdrawal. This unexpected incidence of chronic GVHD might be linked to the high number of CD3+ cells in the graft, contributing to a favourable GVL effect.

[Mean renal transit time of I-123 orthoiodohippurate in normotensive and hypertensive subjects]. / Il tempo medio di transito renale dell'ortoiodioippurato-I123 in soggetti normotesi ed in soggetti ipertesi.

The author executed the renography with I-123-orthoiodohippurate in 18 normotensive patients and in 12 genuine hypertensive patients. The analysis of the renography allowed the computation of the mean kidney transit time of the I-123-orthoiodohippurate and the effective renal plasma flow. The two parameters were regarded cumulatively for both kidneys. The effective renal plasma flow was divided for the body mass index and in this way the flow for unit of the body mass index was computed. The results were tested with the t of Student and either the mean kidney transit time either the effective renal plasma flow were significantly decreased in the hypertensive patients. The author explains this observation saying that in the tested hypertensive subjects the turnover of the I-123-orthoiodohippurate is increased.

Treatment of normal donors with rhG-CSF 16 micrograms/kg for mobilization of peripheral blood stem cells and their apheretic collection for allogeneic transplantation.

BACKGROUND: Utilization of peripheral blood stem cells (PBSC) in allogeneic transplantation requires a method for their mobilization and collection that is not inconvenient for the donor. METHODS: We administered rhG-CSF (filgrastim) 16 micrograms/kg subcutaneously for 4 days in five normal subjects (age 18-31, M = 3, F = 2), previously selected as HLA-identical donors of siblings with leukemia. All the donors gave written informed consent. On days 4 and 5 (in one donor on day 6 too), 10:l leukapheretic collection was performed with a CS-3000 (Baxter) or an AS-104 (Fresenius) cell separator through the antecubital vein. RESULTS: The WBC count reached a median peak of 57.0 x 10(9)/L on day 5. The peripheral blood CFU-GM peaked to a median level of 8908/mL on day 5 with a median increase over baseline values of 39.1 times. The CD34+ cells peaked to (median) 147.0 x 10(6)/L on day 4 with a median increase of 65.3 times. A lesser enrichment was recorded for BFU-E (median increase 12.7 times) and CFU-GEMM (median increase 15.2 times). Even CD3+ and CD56+CD3- cells increased (median 1.7 and 1.5 times, respectively). A median of 771 x 10(8) MNC (range 672-1378), 116.4 x 10(6) CFU-GM (range 47.7-145.1) and 754 x 10(6) CD34+ cells (range 477-2599) were apheretically collected. Concerning side effects, mild to moderate back pain and general minor discomfort were reported by all donors. The platelet level regularly but transiently decreased after completion of the apheretic procedures with a median nadir of 69 x 10(9)/L (range 43-126) on (median) day 7, but in no case did thrombocytopenia cause bleeding. The thrombocytopenia was more pronounced with the CS-3000 than the AS-104 apparatus. CONCLUSIONS: rhG-CSF 16 micrograms/kg x 4 days is an efficient schedule for PBSC mobilization in healthy donors, but lower doses and even a single apheresis procedure might prove similarly adequate.

Engraftment kinetics and long-term stability of hematopoiesis following autografting of peripheral blood stem cells.

BACKGROUND: We analyzed short-term and sustained hematopoietic reconstitution after high-dose therapy with peripheral blood stem cell (PBSC) support in patients with various malignant disorders. METHODS: Fifty-six patients, all with malignant hematologic disorders, were autografted between 1989 and 1994 using PBSC (47 pts) or PBSC + bone marrow (BM) cells (9 pts). PBSC were collected after mobilization with chemotherapy +/- hematopoietic growth factors (GF). RESULTS: All patients engrafted > 0.5 x 10(9)/L polymorphonuclear cells (PMN) and > 50.0 x 10(9)/L Plt at a median of 12 (8-32) and 13 (9-365) days, respectively. Thirty-nine patients were evaluable for long-term graft performance, and their hematologic values at 30 and 100 days, at 6 months and at 1, 2, 3, 4 and 5 years were retrospectively analyzed. Steady counts were recorded over the years. None of the patients had late graft failure. CONCLUSIONS: PBSC given after high-dose chemotherapy ensure a fast hematologic recovery with stable graft performance up to five years after autograft. Though this is not definitive proof of the presence of uncommitted stem cells in the PBSC population, it gives further support to the idea that PBSC are as safe as bone marrow for long-term engraftment. A delayed or incomplete recovery of platelets may occur with low PBSC counts or when disease relapse occurs rapidly after autograft.

Mobilization of circulating progenitor cells in multiple myeloma during VCAD therapy with or without rhG-CSF.

BACKGROUND: Circulating progenitor cells (CPC), when infused in large numbers, rapidly repopulate the marrow after myeloablation with high-dose therapy. In multiple myeloma (MM), as in other disorders, different chemotherapy regimens, including single-as well as multiple-agent chemotherapy, with or without hemopoietic growth factors, have been proposed to mobilize these progenitor cells into the blood. Here we report our experience with a drug combination called VCAD and compare the results to those obtained by adding rhG-CSF to the same combination. METHODS: Fourteen MM patients were given one course of VCAD, a chemotherapy association of vincristine 2 mg, cyclophosphamide 4 x 0.5 g/m2, adriamycin 2 x 50 mg/m2 and dexamethasone 4 x 40 mg, before undergoing apheresis to collect CPC for autografting. Seven also received rhG-CSF (filgrastim) 5 mcg/kg/day over the period of apheresis. These latter were allocated to rhG-CSF treatment sequentially from the time the drug became available for clinical use. RESULTS: Following VCAD-induced pancytopenia, CFU-GM peaked at a median of 853/mL (range 96-4352; 7.6 times basal level). RhG-CSF administration increased CFU-GM levels but not significantly. With rhG-CSF the CFU-GM peak was reached sooner, toxicity was reduced and granulocytopenia less protracted. Fewer aphereses were run in the rhG-CSF group, there were higher yields per single run, and patients began and completed their collection program more quickly. CONCLUSIONS: The VCAD association is able to mobilize CPC in patients with MM, and rhG-CSF is recommended as a fundamental part of the priming schedule.

[Evaluation of 3 calculation methods to compute the PER, PFR, TPER, TPFR with equilibrium radioisotopic angiocardiography]. / Valutazione di tre metodi di calcolo per computare PER, PFR, TPER, TPFR con l'angiocardiografia radioisotopica all'equilibrio.

The author wanted to test 3 FITS to compute the peak ejection rate, the time of the peak ejection rate, the peak filling rate, the time of the peak filling rate from the left ventricle volume curve computed by means of the multigated radio nuclide angiography; the aim of the test was to ascertain the differences between the 3 methods and the differences between them for medical applications. 25 patients were tested and they were divided as follows: 5 cases of hypertension, 2 cases of obesity, 9 cases of alimentary diabetes, 3 cases of coronary heart disease, 6 cases with other diseases. The investigated FITS were: 1) the FIT that computes the derivative curve of the volume curve; 2) the FIT that computes the derivative equation of the volume curve and that interpolates it to a polynomial; 3) the FIT of Fourier. A discriminant analysis was performed and the following observations were made: according to a significant probability P < 0.05, FIT 1 classified 40% of the cases, FIT 2 classified 48% of the cases, FIT 3 classified 64% of the cases. A Box's M test was performed and was significant for FIT 3 and FIT 2 but not for FIT 1. In conclusion the test of the 3 FITS showed that FIT 3 is a better discriminant between the diverse diseases.

Three-dimensional surface display in blood pool gated SPECT.

In 14 patients (4 in good health and 10 with coronary heart disease) a blood pool gated single photon emission computed tomography (SPECT) was executed. The transaxial slices of the cardiac blood pool were reconstructed. A three-dimensional surface display was employed for the analysis of the tomographic data. A fixed distance, a fixed threshold (50%), and some different planes of view were employed. The test permitted visualization of the ventricular and the atrial movements in all patients. The right ventricle was clearly seen in the right anterior oblique plane of view. The aortic beating was seen. In normal patients the left ventricle, clearly seen in left anterior oblique plane, shrank to a thin shank. In 4 patients with septum infarct the blood pool was seen to persist in the septum area in front of the lateral wall shrinking (akinesis). The opposite happened in patients with anterolateral wall coronary artery disease. Three-dimensional surface display of blood pool gated SPECT shows a real three-dimensional picture of the dynamic heart and is a new noninvasive approach to the heart patient.