Biomedical subjects
Publications and source records attributed to M Salvatore.
Tc-99m sestamibi imaging was performed in two patients with multiple myeloma. Focal areas of increased uptake in one patient and diffuse skeletal uptake in the second patient were found. Tc-99m sestamibi appears to identify bone marrow and osteolytic involvement in multiple myeloma.
PURPOSE: To compare brain perfusion and synaptic density in Alzheimer's disease assessed using I-123 iomazenil SPECT with brain perfusion assessed using Tc-99m HMPAO SPECT. MATERIALS AND METHODS: Early and delayed I-123 iomazenil SPECT images acquired 20 and 180 minutes after injection were compared with Tc-99m HMPAO SPECT studies acquired 15 to 20 minutes after injection in five patients with Alzheimer's disease. RESULTS: Visual analysis of I-123 iomazenil images showed more severe (n = 4) and extensive (n = 3) defects than did Tc-99m HMPAO. Semiquantitative analysis was performed by normalizing the uptake of Tc-99m HMPAO and I-123 iomazenil in individual brain regions in the cerebellum and expressing these values as a ratio of the occipital regions. The analysis of brain regional ratios in Tc-99m HMPAO studies showed a low but significant correlation with ratios of delayed (r = 0.325, P < 0.05) images in the I-123 iomazenil studies. Furthermore, when compared with Tc-99m HMPAO, early (P < 0.01) and delayed mean ratios (P < 0.05) were significantly less in the frontal regions; early mean ratios were significantly less in the temporal regions (P < 0.05), and delayed (P < 0.05) mean ratios were significantly less in the parietal regions. CONCLUSIONS: Tc-99m HMPAO images were better correlated with I-123 iomazenil images, indicating cortical synaptic density (delayed images). I-123 iomazenil SPECT in patients with Alzheimer's disease provided more sensitive information than Tc-99m HMPAO, allowing evaluation of brain perfusion and synaptic density.
The aim of the study was to investigate the effects of 1-yr treatment with octreotide (OCT) on left ventricular diastolic and systolic function, assessed at rest and during physical exercise by gated blood pool cardiac scintigraphy, in 30 patients with active acromegaly. OCT was initially given at a dose of 0.05-0.1 mg, 3 times daily, and the dose was subsequently increased to achieve GH/insulin-like growth factor I (IGF-I) normalization. Hormone normalization after treatment was considered when basal and/or oral glucose test-suppressed GH values were below 2.5 and 1 microg/L, respectively, and IGF-I values were within the normal range for age. To evaluate the response to OCT treatment in terms of cardiac performance, the 30 patients were divided into 2 groups on the basis of normalized (in 13 patients) or nonnormalized (in 17 patients) circulating GH and IGF-I levels. At study entry, hypertension was found in 6 patients (20%), abnormal left ventricular diastolic filling was found in 12 patients (40%), and impaired left ventricular ejection fraction was found in 2 patients at rest (6.6%) and in 18 patients at peak exercise (60%). Before OCT treatment, exercise duration ranged from 6-10 min, and exercise workload ranged from 50-125 watts. After 1-yr treatment with OCT, a significant decrease in circulating GH and IGF-I levels was achieved in all patients, but normalization was obtained only in 13 of 30 patients. In patients achieving circulating GH and IGF-I normalization after OCT treatment but not in those with persistently elevated hormone levels, a significant decrease in heart rate, both at rest (from 75.7 +/- 3.3 to 66.5 +/- 2.9 beats/min; P < 0.01) and after exercise (from 137.5 +/- 4.9 to 123.7 +/- 4.1 beats/min; P < 0.01), and a significant increase in left ventricular ejection fraction, both at rest (from 56.5 +/- 1.8% to 66.5 +/- 2.2%; P < 0.01) and after exercise (from 52.6 +/- 2.4% to 67.1 +/- 1.7%; P < 0.01), were found. In the 17 patients who had persistently high circulating GH and IGF-I levels after 1 yr of OCT treatment, left ventricular ejection fraction was unchanged at rest but was significantly reduced after exercise compared to the basal value (from 64.9 +/- 2.4% to 57.2 +/- 2.6%, P < 0.01); systolic blood pressure at rest was significantly increased (from 128.5 +/- 4.9 to 141.2 +/- 5.4 mm Hg; P < 0.05). In these 17 patients, the ejection fraction response to exercise was significantly impaired, mostly in those less than 40 yr of age (from 11.6 +/- 3.2% to -0.3 +/- 5.6%; P < 0.05). In particular, among 9 patients who had a normal response to exercise at study entry, 6 developed an abnormal response after 1 yr. Left ventricular diastolic filling was unchanged by OCT treatment in all patients. Exercise duration (only in young patients from 7.5 +/- 0.5 to 9.3 +/- 0.7 min; P < 0.05) and exercise workload (in all 13 patients from 80.8 +/- 6.4 to 92.3 +/- 5.9 watts; P < 0.05) were significantly increased in the group of patients with normalized GH and IGF levels, but not in the remaining 17 (from 7.6 +/- 0.4 to 7.5 +/- 0.4 min and from 89.9 +/- 5.5 to 84.4 +/- 4.5 watts, respectively). In conclusion, the results of the present study indicate that suppression of basal or glucose-suppressed GH levels below 2.5 or 1 microg/L, respectively, together with normalization of plasma IGF-I levels for 1 yr are followed by a significant improvement, but not complete normalization, of left ventricular ejection fraction either at rest or at peak exercise without significant changes in diastolic filling. By contrast, the persistence for 1 yr of elevated hormone levels caused a significant increase in systolic blood pressure and impaired cardiac performance. These data suggest that prolonged suppression of circulating GH and IGF-I levels could normalize cardiac performance and probably reverse the poor prognosis for cardiovascular disease in acromegaly.
Several evidences indicate that GH and/or insulin-like growth factor I (IGF-I) are involved in the regulation of cardiovascular function. In patients with childhood and adulthood-onset GH deficiency (GHD), the impairment of cardiac performance is manifest primarily as a reduction in the left ventricular (LV) mass (LVM), inadequacy of LV ejection fraction both at rest and at peak exercise, and abnormalities of LV diastolic filling. No study has been reported to date in elderly GHD patients that investigated cardiac function. In particular, it is unknown whether cardiac function is modified in accordance with patients' age as a physiological response to aging, as in normal subjects the rate and extent of LV filling are reduced with age. This study was designed to evaluate heart morphology and function, by echocardiography and equilibrium radionuclide angiography, respectively, in rigorously selected elderly patients with GHD but without evidence of other complications able to affect cardiac performance. Eleven patients with hypopituitarism (6 men and 5 women, aged 60-72 yr) and 11 sex- age- and body mass index-matched healthy subjects entered this study. None of the patients and controls presented with or had previously suffered from other concomitant diseases, such as diabetes mellitus, coronary artery diseases, long-standing hypertension, and hyperthyroidism, which could affect cardiac function. All patients had been previously operated on via the transsphenoidal and/or transcranic route for nonfunctioning pituitary adenoma, meningioma, or craniopharyngioma, and 6 of them had been irradiated. Eight patients had FSH/LH insufficiency, 5 had TSH insufficiency, and 6 had ACTH insufficiency, appropriately replaced. All subjects were tested with the combined arginine plus GHRH test showing a GH response below 9 microg/L. No significant difference was found in plasma IGF-I levels (49.2 +/- 8.5 vs. 71.8 +/- 7.5 microg/L) between patients and controls. However, IGF-I levels were lower than the normal range in 8 patients and 3 controls. Interventricular septum thickness (9.1 +/- 0.2 vs. 9.1 +/- 0.2 mm), LV posterior wall thickness (9.1 +/- 0.2 vs. 9.0 +/- 0.2 mm), and LVM after correction for body surface area (97.6 +/- 1.8 vs. 99.9 +/- 1.5 g/m2) were similar in patients and controls. Similarly, the LV ejection fraction at rest was similar in patients and controls (57.1 +/- 2% vs. 63.2 +/- 2.5%; P = NS), and it was normal (> or = 50%) in all controls and in 10 of 11 patients. By contrast, the LV ejection fraction at peak exercise was markedly depressed in elderly GHD patients compared to age-matched controls (51 +/- 2.5% vs. 73.3 +/- 3%; P < 0.001). A normal response (> or = 5% increase compared to basal value) of LV ejection fraction at peak exercise was found in 8 controls (72.7%) and in 2 of 11 patients (18.2%). No difference was found in the peak rate of LV filling, whether peak filling rate was normalized to end-diastolic volume (2.5 +/- 0.2 vs. 2.6 +/- 0.2 end-diastolic volume/s) or stroke volume (4.3 +/- 0.3 vs. 4.0 +/- 0.3 stroke volume/s), between patients and controls. Finally, exercise duration was significantly shorter in elderly GHD patients than in age-matched controls (7.2 +/- 2.1 vs. 9.1 +/- 0.2 min; P < 0.01). In the patient group, the GH peak after arginine plus GHRH test was significantly correlated with the LV ejection fraction at rest (r = 0.822; P < 0.01), whereas IGF-I was significantly correlated with the peak rate of LV filling whether the peak filling rate was normalized to end-diastolic volume (r = -0.863; P < 0.001) or stroke volume (r = -0.616; P < 0.05) or expressed as the ratio of peak filling rate to peak ejection fraction rate (r = -0.736; P < 0.01). Disease duration was significantly correlated with heart rate at peak exercise (r = 0.614; P < 0.05) and with systolic and diastolic blood pressures both at rest (r = 0.745; P < 0.01 and r = 0.650; P < 0.05) and at peak exercise (r = 0.684; P < 0.05 and r =
The aim of this study was to evaluate the impact of age and disease duration on cardiac performance in acromegaly. To address these issues, the left ventricular function at rest and during physical exercise was assessed by equilibrium radionuclide angiography in 40 rigorously selected patients with active acromegaly but without evidence of other complications able to affect heart function and in 32 healthy controls. Patients and controls were divided in two groups, on the basis of age below and above 40 yr. Circulating GH and insulin-like growth factor-I levels were significantly increased in patients, compared with controls, but were similar in the two groups of patients. At peak exercise, the systolic blood pressure was significantly higher in elderly patients (P < 0.001), whereas diastolic blood pressure was significantly higher in young patients than in age-matched controls (P < 0.01). Heart rate at peak exercise was significantly higher in young than in elderly patients and controls (P < 0.01), without any evidence of arrhythmia in both groups. The left ventricular ejection fraction at rest was normal (>50%) in all but 2 patients and in all controls. The left ventricular ejection fraction at peak exercise was significantly decreased in elderly, compared with young, patients (P < 0.01) and in age-matched controls (P < 0.001). A normal response of the left ventricular ejection fraction to exercise was found in 12 of 40 patients (30%) and in 28 of 32 controls (87.5%) (chi2, 5.764; P < 0.01). Exercise-induced changes in left ventricular ejection fraction were significantly decreased in young (+5.2 +/- 4.4% vs. +21.3 +/- 3.4%, P < 0.005) and elderly patients (-10.2 +/- 2.8% vs. +13.7 +/- 2.7%, P < 0.0001), as compared with age-matched controls. The peak rate of left ventricular filling was significantly higher in young, than in elderly, patients whether peak filling rate was normalized to end-diastolic volume (P < 0.001), or stroke volume (P < 0.0001), or expressed as the ratio of peak filling rate to peak ejection rate (P < 0.001). The peak rate of left ventricular filling was significantly decreased in elderly patients, compared with young patients and age-matched controls, whether peak filling rate was normalized to end-diastolic volume (P < 0.01), or stroke volume (P < 0.005), or expressed as the ratio of peak filling rate to peak ejection rate (P < 0.001). In the patient group, the left ventricular ejection fraction at peak exercise was significantly correlated with age (r = -0.33, P < 0.05), estimated disease duration (r = -0.34, P < 0.05), exercise-induced changes of the left ventricular ejection fraction (r = 0.34, P < 0.05), and the peak rate of left ventricular filling, whether peak filling rate was normalized to end-diastolic volume (r = 0.33, P < 0.05). Age and estimated disease duration were both significantly correlated with the peak rate of left ventricular filling, whether peak filling rate was normalized to end-diastolic volume (r = 0.55, P < 0.001 and r = -0.49, P < 0.001, respectively), or stroke volume (r = 0.5, P < 0.001 and r = -0.57, P < 0.001, respectively), or expressed as the ratio of peak filling rate to peak ejection rate (r = 0.56, P < 0.0001 and r = -0.52, P < 0.001, respectively). In the control group, the left ventricular ejection fraction at peak exercise was significantly correlated with the left ventricular ejection fraction at rest (r = 0.54, P < 0.01), exercise-induced changes of the left ventricular ejection fraction (r = 0.57, P < 0.001), but neither with age nor peak rate of left ventricular filling at all measurements. In conclusion, left ventricular performance is more frequently preserved in young patients with a short disease duration, although the left ventricular response to exercise was already reduced, as compared with controls. (ABSTRACT TRUNCATED)
The aim of this open prospective randomized study was to evaluate the effect of a 6-month treatment with alendronate on the bone mineral density (BMD) at lumbar spine in patients with central diabetes insipidus. Eighteen patients with central diabetes insipidus and 18 sex- and age-matched healthy subjects entered this study. At study entry, all subjects underwent BMD assessment at the lumbar spine and measurement of serum osteocalcin (OC) and cross-linked N-telopeptides of type I collagen (Ntx). Thereafter, 9 of the 18 patients were randomized to receive treatment with alendronate at a dose of 10 mg, orally, once daily for 6 months (group 1), whereas the remaining 9 patients did not receive any treatment affecting bone status during this period (group 2). After 6 months, bone metabolism and bone density study were repeated in all patients. At baseline, lumbar BMD values (0.86+/-0.03 vs. 1.01+/-0.02 g/cm2; P<0.001) and serum OC levels (4.7+/-0.3 vs. 7.9+/-0.2 microg/L; P<0.001) were significantly lower, whereas urinary Ntx levels were significantly higher [72.0+/-1.9 vs. 64.6+/-1.7 nmol bone collagen equivalents (BCE)/nmol creatinine (Cr); P<0.01] in patients than in controls. After randomization, no difference in lumbar BMD, serum OC, or urinary Ntx was found between patients of group 1 and group 2. At the 6 month follow-up, no difference in serum OC levels was found compared to baseline evaluation in patients of both group 1 and group 2. By contrast, a significant decrease in urinary Ntx levels was found in patients of group 1 (70.3+/-3.0 vs. 75.4+/-2.1 nmol BCE/nmol Cr; P<0.05), but not in patients of group 2 (68.8+/-3.3 vs. 68.5+/-3.0 nmol BCE/nmol Cr; P = NS). A significant increase in lumbar BMD values was found in patients of group 1 (0.88+/-0.04 vs. 0.83+/-0.04 g/cm2; P<0.05), whereas a significant decrease in lumbar BMD values was found in patients of group 2 (0.86+/-0.05 vs. 0.89+/-0.05 g/cm2; P<0.05). Lumbar BMD increased 7.0+/-1.5% in patients of group 1 and decreased 4.2+/-1.8% in patients of group 2 (P<0.001). In conclusion, this study demonstrated that a 6-month treatment with alendronate in patients with central diabetes insipidus was effective in significantly improving BMD at the lumbar spine, which was significantly worsened in untreated patients. Therefore, alendronate treatment could be used in patients with central diabetes insipidus with documented osteopenia or osteoporosis.
OBJECTIVE: The aim of this study was to differentiate benign from malignant adrenal tumors using positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) in patients with unilateral adrenal masses originally detected by CT or MR imaging. CONCLUSION: PET imaging with FDG can metabolically characterize adrenal masses. Abnormally increased FDG uptake in adrenal malignancies allows one to differentiate these abnormalities from benign lesions. Whole-body PET can also reveal extraadrenal tumor sites in patients with malignant tumors, using a single imaging technique for accurate disease staging.
UNLABELLED: An original method for simultaneous display of functional and anatomic images, based on frequency encoding (FE), merges color PET with T1-weighted MR brain images, and grayscale PET with multispectral color MR images. A comparison with two other methods reported in the literature for image fusion (averaging and intensity modulation techniques) was performed. METHODS: For FE, the Fourier transform of the merged image was obtained summing the low frequencies of the PET image and the high frequencies of the MR image. For image averaging, the merged image was obtained as a weighted average of the intensities of the two images to be merged. For intensity modulation, the red, green and blue components of the color image were multiplied on a pixel-by-pixel basis by the grayscale image. A comparison of the performances of the three techniques was made by three independent observers assessing the conspicuity of specific MRI and PET information in the merged images. For evaluation purposes, images from seven patients and a computer-simulated MRI/PET phantom were used. Data were compared with a chi-square test applied to ranks. RESULTS: For the depiction of MRI and PET information when merging color PET and T1-weighted MR images, FE was rated superior to intensity modulation and averaging techniques in a significant number of comparisons. For merging grayscale PET with multispectral color MR images, FE and intensity modulation were rated superior to image averaging in terms of both MRI and PET information. CONCLUSION: The data suggest that improved simultaneous evaluation of MRI and PET information can be achieved with a method based on FE.
BACKGROUND AND OBJECTIVE: The tracer tachnetium-99m-2-methoxy-isobutyl-isonitrile (Tc99m-sestaMIBI) has recently been shown to concentrate in some neoplastic tissues, including myeloma. We investigated the diagnostic capacity and limits of this procedure in tracing focal myeloma lesions, and compared them with those of conventional radiological procedures (Xr). DESIGN AND METHODS: We studied 55 patients suffering from multiple myeloma (MM) or solitary plasmacytoma in different stages and clinical conditions, or from monoclonal gammopathy of undefined significance (MGUS), by whole body scans obtained 10 minutes after injection of 555 MBq of Tc99m-sestaMIBI. Scans were defined as normal (physiological uptake only), diffuse (presence of bone marrow uptake), or focal (localized areas of uptake), and were compared to conventional skeletal Xr. RESULTS: Thirty patients showed no focal areas of Tc99m-sestaMIBI uptake; this group consisted of 5 patients with MGUS, 6 with MM in stage IA and 2 in stage IIA, 11 patients studied after effective chemotherapy and 6 in early relapse. Twenty-five patients showed one or more spots of focal uptake: all of them had active disease (untreated, resistant or relapsing MM). In the setting of tracing focal lesions, Tc99m-sestaMIBI scans were concordant with the radiological examination in 38 patients and discordant in 17. Among the latter, in 4 cases Tc99m-sestaMIBI revealed focal lesions not detected by Xr, and in 13 cases lytic areas detected by Xr did not show Tc99m-sestaMIBI uptake. INTERPRETATION AND CONCLUSIONS: In untreated patients, the number of lesions revealed by Tc99m-sestaMIBI was comparable to that shown by Xr, while in pretreated patients Tc99m-sestaMIBI traced a number of lesions lower than that detected by Xr. The reason for this discrepancy is that Tc99m-sestaMIBI traces only active lesions. Tc99m-sestaMIBI limitations in identifying focal lesions may derive from the dimension of the smallest traceable lesion (about one centimeter), and from the possibility that focal plasma cell localizations in collapsed bone may not be visualized due to inadequate vascularization. Tc99m-sestaMIBI scintigraphy is an interesting tool for diagnosing, staging and following up focal myeloma lesions, in the bone as well as in soft tissues. It is more specific than conventional Xr in identifying sites of active disease.
INTRODUCTION: CT-guided fine needle aspiration biopsy (FNAB) is known to improve diagnosis of expansile abdominal lesions, especially relative to more invasive procedures like explorative laparotomy. FNAB is not commonly used in pediatric patients because of their poor collaboration and of associated risks. We investigated the feasibility of FNAB in the pediatric age. MATERIAL AND METHODS: Over a 2-year period, we performed CT-guided FNAB of 21 abdominal lesions in a series of pediatric patients ranging in age 10 days to 14 years. Thirteen lesions were in intraperitoneal and 8 in retroperitoneal sites. CT had been performed in all patients but had failed to make a diagnosis. Cytologic samples were obtained with 22-23 G needles; the cytologist was always present to ensure adequate sampling. Follow-up CT was performed to assess the possible onset of complications. RESULTS: First-pass diagnosis was made in 14 of 21 biopsies and second-pass diagnosis in 5; histology was needed in three cases. Cytologic findings were compared with postoperative histologic results in 13 cases; clinical follow-up and further instrumental studies confirmed the diagnosis in nonsurgical patients. CONCLUSIONS: CT-guided FNAB can be performed in pediatric patients with accuracy and confidence. These patients' age calls for great skills of the operator and possible contraindications must be accurately evaluated; complications must not be neglected. FNAB should be performed during CT examination because young patients often require anesthesia. The pathologist's presence during biopsy permits to repeat sampling, if necessary, without repeating the anesthesia. CT-guided FNAB is a valid alternative to explorative laparotomy in the workup of expansile abdominal masses also in pediatric patients.
The most well-characterized mechanism of multidrug resistance (MDR) involves P-glycoprotein (Pgp), a transmembrane protein acting as an ATP-dependent drug efflux pump. The recognition of 99mTc-Sestamibi and other lipophilic cations as transport substrates for Pgp provided the necessary tool for the clinical assessment of Pgp function in patients with cancer. Many clinical studies from different institutions and trials including a variety of malignancies indicate that both tumor uptake and clearance of 99mTc-Sestamibi are correlated with Pgp expression and may be used for the phenotypic assessment of multidrug resistance. Although both parameters may predict tumor response to chemotherapy, the extraction of efflux rate constants appeared to provide a more direct index of Pgp function as compared to tracer uptake ratio allowing to trace a continuous spectrum of drug transport activity. Preliminary studies reported the use of MDR imaging agents to monitor the modulating ability of revertant compounds. Although the results support the feasibility of this approach, the alteration of tracer pharmacokinetics induced by the modulators certainly constitutes a challenge in the development of a simple functional test suitable in clinical practice. The extension of the acquired imaging methodology to tumors with redundant intrinsic resistant mechanisms such as lung cancer requires further investigations on the relative contribution and clinical relevance of each mechanism. Due to the multifactorial nature of the phenomenon, the development of new tracers with substrate specificity for other known drug transporters would hopefully help to dissect the complex array of cellular mechanisms contributing to treatment failure.
The thymus is a bilobed lymphoid organ the morphology of which varies considerably with age as a result of a process of fatty infiltration occurring after puberty. Although several diseases can arise in the thymic parenchyma, including germ cell and neuroendocrine tumours, primitive epithelial neoplasms (thymomas) are the most common neoplasms and account for almost 10% of mediastinal masses. Thymomas are usually benign but can be locally invasive. Up to 30% of patients with a thymoma have myasthenia gravis, which is more commonly associated with thymic hyperplasia. The latter results in a symmetric diffuse enlargement of the thymus. However, thymic hyperplasia can be histologically found in up to 50% of normal-sized thymuses on computed tomography (CT). CT is much more accurate in detecting thymomas than it is in detecting thymic hyperplasia, although CT findings may be unspecific. CT can be exhaustive in the case of an encapsulated thymoma (65% of all thymomas), which appear as a solid homogeneous mass with a slight contrast enhancement and a well-defined surrounding fat plane. These tumours rarely recur after surgery. CT can also accurately detect a spread through the capsule into the adjacent mediastinal fat, which characterizes invasive thymomas (35%). These, however, are best evaluated by magnetic resonance imaging (MRI). On T1-weighted MR scans the thymus is well delineated against the mediastinal fat, whereas marked inhomogeneity of the signal may appear on T2-weighted images as a result of areas of cystic degeneration in the tumour mass. The superior contrast resolution of MRI and the multiplanar images that can be produced with it are well suited for documenting the mediastinal spread of invasive thymomas. MRI depicts accurately pleural and/or pericardial implants as well as the involvement of great vessels, offering considerable aid in the planning of surgery.
Thymomas are rare neoplasms that are usually associated with parathymic syndromes, pure red cell aplasia, myasthenia gravis, hypogammaglobulinaemia and other mainly immunological disorders. Therefore, the management of thymoma patients is often complex and presents many diagnostic and therapeutic issues. Controversies concerning the definition of the histological subtypes and the role played by thymoma-associated syndromes are of primary importance in determining the oncological approach. Although low-stage thymomas have a high percentage of recovery, thymomas which are locally advanced, metastatic or previously treated with standard therapeutic options have no well-defined and effective treatment approaches. The data previously described by us on somatostatin receptor scintigraphy showing high uptake of indium-labelled octreotide by thymic masses and the successful treatment of a patient with thymoma and pure red cell aplasia with octreotide and prednisone has provided us the rationale for using such treatment in patients with advanced thymoma.
Borna disease virus (BDV) causes persistent central nervous system infection and behavioral disturbances in warm-blooded animals. Protein interaction studies were pursued to gain insight into the functions of the putative nucleoprotein (N), phosphoprotein (P), atypical glycoprotein (gp18), and X protein (X) of BDV. Coimmunoprecipitation experiments indicated that N and P, and P and X, form complexes in infected cells. Two-hybrid analyses confirmed interactions between P and P, P and X, and P and N, but not between P and gp18, N and gp18, X and gp18, or X and N. Analysis of P truncation mutants identified three nonoverlapping regions important for oligomerization (amino acids (aa) 135-172), and binding to X (aa 33-115) or N (aa 197-201). Coexpression of X stimulated oligomerization of P but decreased N-P complex formation. Immunocytochemistry of transfected noninfected CHO cells demonstrated that the distribution of X is dependent upon the presence of P-X expressed alone was found predominantly in the cytoplasm whereas coexpression of X and P resulted in nuclear localization. Immunocytochemistry of infected cells revealed nuclear colocalization of P and X. Interactions of P, N, and X may have implications for regulation of BDV transcription/replication and ribonucleoprotein assembly.
Diastolic dysfunction is common in hypertrophic cardiomyopathy (HC). Previous studies suggest that Doppler transmitral flow velocity profiles, and the left atrial (LA) M-mode echogram can be used noninvasively to evaluate left ventricular (LV) diastolic function. However, this has not been proved in HC. In this study we determined the relation of Doppler transmitral flow velocity profiles and the LA M-mode echograms to invasive indexes of LV diastolic function in patients with HC. We studied 25 patients with HC, while off drugs, and calculated LA global and active fractional shortening and the slope of both early and late displacement of the posterior aortic wall during LA emptying by M-mode echocardiography. We calculated peak velocity of early (E) and atrial (A) filling, E to A ratio, and E-wave deceleration time by pulsed Doppler echocardiography, and simultaneous radionuclide angiography, LV pressures, time constant of isovolumic relaxation tau, and the constant of chamber stiffness k by cardiac catheterization. The time constant of isovolumic relaxation tau correlated with the slope of early posterior aortic wall displacement (r = 0.59; p <0.01). LV end-diastolic pressure correlated with global LA fractional shortening (r = -0.75; p <0.001); the constant of chamber stiffness k correlated with active LA fractional shortening (r = -0.53; p <0.02). In a subset of 13 patients, in whom echocardiography and cardiac catheterization were performed simultaneously, similar results were found. LA M-mode recordings provide a more reliable noninvasive assessment of diastolic function in HC than mitral Doppler indexes.
To assess the inter-study variability of a recently published unsupervised segmentation method (Magn. Reson. Med. 1997;37:84-93), 14 brain MR studies were performed in five normal subjects. Standard deviations for absolute and fractional volumes of intracranial compartments, which reflect the experimental variability, were smaller than 16.5 ml and 1.1%, respectively. By comparing the experimental component of the variability with the variability observed in our reference database, an estimate of the biological variability of the intracranial fractional volumes in the database population was obtained.
The role of coronary revascularization of dysfunctional myocardium with preserved thallium-201 uptake in determining the prognosis in patients after myocardial infarction remains to be defined. This study was designed to evaluate the effects of successful revascularization on survival and left ventricular (LV) function in patients with previous myocardial infarction and evidence of dysfunctional but still viable myocardium at rest-redistribution 201Tl imaging. Seventy-six consecutive patients with LV dysfunction related to previous myocardial infarction and evidence of viable myocardium at rest-redistribution 201Tl tomography were followed for 17+/-8 months. LV ejection fraction (EF) was assessed by radionuclide angiography at baseline and after 13+/-2 months. Thirty-nine patients were revascularized (group A) and 37 treated medically (group B). During the follow-up there were nine cardiac deaths. Survival rate was 97% in group A and 66% in group B (P<0.01). By Cox multivariate analysis, the extent of viable myocardium was the best predictor of cardiac death (chi2=8.67, P<0.01) and provided additional information to clinical and functional data (P<0.01). The inclusion of revascularization as a variable improved the global chi2 of the model from 14.1 to 21.9 (P<0.01). At follow-up, EF had improved by >/=5% in 16 patients. By multivariate logistic analysis, the extent of viable myocardium was the best predictor of EF improvement (chi2=15.49, P<0.001) and provided additional information to clinical and functional data (P<0.01). The inclusion of revascularization as a variable improved the global chi2 of the model from 16.8 to 22.5 (P<0.01). These results demonstrate that the total extent of dysfunctional myocardium with preserved 201Tl uptake is the strongest predictor of cardiac death in patients after myocardial infarction. Successful revascularization of dysfunctional but viable myocardium improves survival and LVEF in such patients.
Technetium-99m 2-methoxyisobutylisonitrile (99mTc-MIBI) has been proposed as a potential tracer in patients with multiple myeloma (MM). The aims of this study were to evaluate the incidence of various patterns of diffuse 99mTc-MIBI uptake in patients with MM, to assess their relationship with clinical status and stage of disease, and to try to clarify the meaning of the diffuse bone marrow uptake of 99mTc-MIBI. Thirty-nine consecutive patients with MM were studied. Twenty-nine of these patients had active disease (13 in stage I, ten in stage II, and six in stage III) and ten were in remission after chemotherapy. Anterior and posterior whole-body scans were obtained 10 min after i.v. injection of 555 MBq of 99mTc-MIBI. The scans were classified as showing: pattern N, when only physiological uptake was present; pattern D, when diffuse bone marrow uptake was observed; pattern F, when areas of focal uptake of the radiotracer were evident; or pattern D+F, when both D and F patterns were observed. Diffuse bone marrow uptake was scored according to extension and intensity. Seven of the 39 patients (18%) showed pattern N, 18 (46%) pattern D, 2 (5%) pattern F, and 12 (31%) pattern D+F. Of the 32 patients with a positive 99mTc-MIBI scan (i.e. showing pattern D, F or D+F), 29 (91%) had active disease. Only three patients in remission showed pattern D, but with a very low bone marrow uptake score. Both extension and intensity of diffuse bone marrow uptake correlated with the amount of the monoclonal component and the percentage of bone marrow plasma cells. The distribution of the 99mTc-MIBI uptake patterns differed among patients in different stages of disease. Using as criteria for advanced stage the presence of either focal uptake (pattern F or D+F) or pattern D with a high score, high (90%) diagnostic accuracy was obtained. In conclusion, the patterns of 99mTc-MIBI uptake in patients with MM are related to both the clinical status and the stage of disease. The presence of focal uptake or of intense diffuse bone marrow uptake suggests that the patient has active and advanced stage disease, while a negative scan in a patient with MM clearly indicates remission.