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Biomedical subjects

A D'Addabbo

Publications and source records attributed to A D'Addabbo.

At least 19 recordsLinked to original sources
PubMed2006

On the statistical assessment of classifiers using DNA microarray data.

BACKGROUND: In this paper we present a method for the statistical assessment of cancer predictors which make use of gene expression profiles. The methodology is applied to a new data set of microarray gene expression data collected in Casa Sollievo della Sofferenza Hospital, Foggia--Italy. The data set is made up of normal (22) and tumor (25) specimens extracted from 25 patients affected by colon cancer. We propose to give answers to some questions which are relevant for the automatic diagnosis of cancer such as: Is the size of the available data set sufficient to build accurate classifiers? What is the statistical significance of the associated error rates? In what ways can accuracy be considered dependant on the adopted classification scheme? How many genes are correlated with the pathology and how many are sufficient for an accurate colon cancer classification? The method we propose answers these questions whilst avoiding the potential pitfalls hidden in the analysis and interpretation of microarray data. RESULTS: We estimate the generalization error, evaluated through the Leave-K-Out Cross Validation error, for three different classification schemes by varying the number of training examples and the number of the genes used. The statistical significance of the error rate is measured by using a permutation test. We provide a statistical analysis in terms of the frequencies of the genes involved in the classification. Using the whole set of genes, we found that the Weighted Voting Algorithm (WVA) classifier learns the distinction between normal and tumor specimens with 25 training examples, providing e = 21% (p = 0.045) as an error rate. This remains constant even when the number of examples increases. Moreover, Regularized Least Squares (RLS) and Support Vector Machines (SVM) classifiers can learn with only 15 training examples, with an error rate of e = 19% (p = 0.035) and e = 18% (p = 0.037) respectively. Moreover, the error rate decreases as the training set size increases, reaching its best performances with 35 training examples. In this case, RLS and SVM have error rates of e = 14% (p = 0.027) and e = 11% (p = 0.019). Concerning the number of genes, we found about 6000 genes (p < 0.05) correlated with the pathology, resulting from the signal-to-noise statistic. Moreover the performances of RLS and SVM classifiers do not change when 74% of genes is used. They progressively reduce up to e = 16% (p < 0.05) when only 2 genes are employed. The biological relevance of a set of genes determined by our statistical analysis and the major roles they play in colorectal tumorigenesis is discussed. CONCLUSIONS: The method proposed provides statistically significant answers to precise questions relevant for the diagnosis and prognosis of cancer. We found that, with as few as 15 examples, it is possible to train statistically significant classifiers for colon cancer diagnosis. As for the definition of the number of genes sufficient for a reliable classification of colon cancer, our results suggest that it depends on the accuracy required.

Aged↗
PubMed2000

Inflammatory response and angiogenesis after percutaneous transmyocardial laser revascularization.

BACKGROUND: The aim of our study was to investigate the inflammatory response immediately after percutaneous transmyocardial laser revascularization (PTMR) along with the underlying mechanism of angiogenesis. METHODS: Patients with angina pectoris underwent coronary angiography and were divided into two groups. Group A (n = 10) included patients with obstructed vessels who received PTMR, whereas group B (n = 5) comprised patients who had normal coronary arteries. Blood levels of neutrophils, procalcitonin, troponin-I, myoglobin, and creatine kinase (CK) mass were evaluated in each patient before angiography and monitored up to 48 hours after the procedure. Six patients were injected with 99mTc-leukoscan approximately 60 to 90 minutes after PTMR. During the 240 to 300 minutes after the radionuclide administration, single photon emission tomography (SPET) was performed and compared with conventional 99mTc-sestamibi-SPET. RESULTS: A significant increase in blood levels of neutrophils and procalcitonin was observed in group A only (p < 0.005). A slight but significant increase of troponin-I was evident in the same group (p < 0.05), and a distinct myocardial uptake of 99mTc-Leukoscan-SPET was observed in each patient along homologous regions treated by PTMR. CONCLUSIONS: The increased amount of neutrophils (both circulating and inside the treated myocardial areas) along with the raised levels of procalcitonin were the immediate reactions to PTMR. This systemic and intramyocardial inflammatory response is the underlying mechanism that gives rise to angiogenesis.

Antibodies, Monoclonal↗
PubMed1998

Pituitary adenomas: the role of 111In-DTPA-octreotide SPET in the detection of minimal post-surgical residues.

Scintigraphy with 111In-DTPA-octreotide (111In-octreotide) enables the localization of tumours with somatostatin receptors on their cell membranes, of which pituitary adenomas are an example. Trans-sphenoidal excision of such tumours is sometimes incomplete and the detection of post-surgical residues is a difficult diagnostic task. In this study, we used 111In-octreotide SPET to visualize pituitary adenomas and their minimal residues. In positive cases, the indirect demonstration of the presence of somatostatin receptors may be decisive for the planning of treatment. 111In-octreotide SPET was able to visualize adenomas in 21 of 27 patients (77.7%) (10 GH-secreting, 10 PRL-secreting and 1 non-secreting). Repeat SPET after the recurrence of clinical symptoms and hormone hypersecretion revealed intense 111In-octreotide uptake by residues in 8 of 10 patients (4 GH-secreting and 6 PRL-secreting). Magnetic resonance imaging was positive in only 3 of these 10 patients. Our results suggest that 111In-octreotide SPET, in combination with other imaging modalities, is useful in the diagnosis and follow-up pituitary adenomas. It ensures better selection of patients for treatment with somatostatin analogues, both pre- and post-operatively, and assists in the development of personalized treatment plans.

Adenoma↗
PubMed1997

Oral erythromycin improves gastrointestinal motility and transit after subtotal but not total gastrectomy for cancer.

BACKGROUND: Erythromycin has been shown to be a powerful prokinetic of the gastrointestinal tract. Little is known about its value to improve motility and transit in gastrectomized patients. METHODS: Thirteen disease-free patients subjected to subtotal gastrectomy and 11 subjected to total gastrectomy for gastric cancer entered the study. Gastrointestinal transit of a standard 99mTc-labelled meal and fasting motility were studied before and after oral erythromycin. RESULTS: In patients who had subtotal gastrectomy mean(s.d.) gastric half-emptying time was 42(14) min before and 26(11) min after erythromycin (P = 0.011). Before erythromycin prolonged rhythmical contractions (3 per min) were recorded in eight patients, sporadic non-organized contractions in two and prolonged bursts of waves in one. After erythromycin, clustered waves resembling a migrating motor complex (MMC) appeared in eight patients, while rhythmic motor activity was unchanged in three. In patients who had total gastrectomy jejunal half-emptying time was 39(18) min before and 45(12) min after erythromycin. In eight patients, frequent MMCs were recorded, peristaltic in four, synchronous in one, antiperistaltic in two, with clusters of non-propagated waves in one. After erythromycin, longer peristaltic MMCs were recorded in three, antiperistaltic MMCs persisted in two, synchronous in one and clusters of non-propagated waves in two. CONCLUSION: Oral erythromycin improves gastrointestinal transit and motility after subtotal gastrectomy. The findings after total gastrectomy are controversial.

Administration, Oral↗
PubMed1995

I-131 MIBG scintigraphy of neuroectodermal tumors. Comparison between I-131 MIBG and In-111 DTPA-octreotide.

An account is given of the results observed with I-131 MIBG scintigraphy in four patients (1 bladder pheochromocytoma, 3 neuroblastomas) chosen on account of their particular clinical and diagnostic interest from a series of 41 apudoma patients examined by means of this technique. In the first patient, the unusual site of the tumor in the posterior wall of the bladder meant that its detection by I-131 MIBG was only possible after catheterization of the bladder. In the second patient, uptake in the metastasis was only evident after removal of the primary tumor. In the third patient, the scintiscan revealed several metastases (some in bone) not detected by CT. In the fourth patient (congenital neuroblastoma), enhanced uptake accompanied the appearance of high plasma catecholamine and urinary vanillylhandelic acid values, suggesting a functional switch from a nonsecreting to a secreting form. a supplementary In-111 DTPA-Octreotide (OCT) scintiscan of this patient demonstrated the presence of somatostatin receptors on the neuroblasts. Thus, this examination would seem particularly useful for the differentiation of nonsecreting neuroblastomas. Its employment in assessment of the therapeutic capacity of OCT itself is also suggested.

3-Iodobenzylguanidine↗
PubMed1995

Scintigraphy in assessment of the feasibility of separation of a set of xipho-omphalopagous conjoined twins.

An account is given of the assessment of a set of xipho-omphalopagous twins by means of Tc-99m microcolloid human serum albumin (HSA) and Tc-99m HIDA scintigraphy before their successful separation. The Tc-99m HSA examination showed the absence of connections between the two hearts and major vessels, as well as the independent vascularization of each liver parenchyma and absence of substantial intrahepatic shunts. Tc-99m HIDA disclosed bile secretion and the existence of intrahepatic ducts in both twins. In one, there was excretion into the intestine and the gallbladder and common bile duct were visualized, whereas in the other excretion was slow, either because of duct hypoplasia or as a result of the connections with the other twin. On separation, it was found that the liver parenchyma was composed of two fused parts (the livers of each twin). In one twin, cholangiography showed the gallbladder and intrahepatic and extrahepatic bile ducts with normal excretion into the intestine and excellent drainage, whereas in the other twin the gallbladder was absent, the common bile duct was hypoplastic, and excretion was poor. The two scintigraphic techniques employed provided evidence of bile duct function and enabled the separation to be planned, while intraoperative cholangiography gave a clear picture of the anatomical details before the reconstruction procedure.

Adult↗
PubMed1994

Casual discovery of Tc-99m MDP uptake for melanoma metastasis in soft tissue.

The authors report the casual discovery in 1991 of a metastasis during Tc-99m MDP imaging of a 57-year-old woman who underwent surgery in 1983 for cutaneous melanoma on the right calf. The scan did not show bone alterations but did reveal an area of hyperactive uptake in the soft tissue of the medial surface of the thigh, where slightly altered pigmentation was also apparent. A subsequent immunoscan with Tc-99m-F(ab')2 225.28S confirmed increased uptake at this site. The lesion was removed and was histologically diagnosed as a skin metastasis from melanoma. Inguinal adenopathy appeared 6 months later. The uptake of Tc-99m MDP by both primary and metastases tumors has been described, although this may be the first report concerning melanoma. The uptake mechanism is not known.

Antibodies, Monoclonal↗
PubMed1994

Renal osteodystrophy with hyperparathyroidism: the diagnostic value of intact parathormone, alkaline phosphatase, osteocalcin and procollagen.

In 27 patients on periodic haemodialysis, serum levels of alkaline phosphatase (ALP), osteocalcin (BGP), intact parathyroid hormone (PTHi) and its two fragments, terminal COOH (PTH-Cter) and middle molecule (PTH-MM), and procollagen type 1 carboxy-terminal extension peptide (P1CP) were measured. The same patients underwent radiography of the skull and of the hands, ultrasonography of the parathyroids and scintigraphy of the skeleton with 99mTc-MDP. The study was completed by the measurement of aluminium (Al) in the blood and the deferoxamine test (DFO). Two groups of patients emerged, one (group A, n = 14) with PTHi greatly increased (201.07 +/- 109.72 pg/mL) and the other (group B, n = 13) with values within the normal range (32.69 +/- 17.06 pg/mL) (p < 0.001). In group A, ALP, BGP and particularly P1CP were increased with a statistically significant difference compared to group B. Specific radiographic alterations were found in 12 patients of group A; 7 patients also had hypertrophy of the parathyroids. There was no difference in the scintigraphic alterations of the skeleton between the two groups. The authors conclude that it is the association of the high values of PTHi with those of the markers of bone metabolism, the normal level of Al, the negativity of the DFO test and the radiological alterations which together allow the diagnosis of renal osteodystrophy with hyperparathyroidism.

Adult↗
PubMed1993

Correlation between bone imaging and the clinical picture in two unsuspected cases of progressive diaphyseal dysplasia (Engelmann's disease).

Progressive diaphyseal dysplasia was incidentally discovered in two patients referred for Tc-99m MDP bone scintigraphy (one for intense sciatica, the other for the detection of breast cancer metastases). Tracer accumulation in the diaphyses of the lower limbs and the base of the skull was accompanied by bone thickening and patency of the medullary cavity, as demonstrated by radiography, MRI, and bone marrow scanning. Comparison of the clinical pictures with the results of instrumental examinations showed that these were cases of sporadic progressive diaphyseal dysplasia of slight and average gravity, respectively. The differentiation of Ribbing's disease is explained and reference also is made to a finding not mentioned in the literature, namely frontal bone resorption lacunules in one patient.

Bone Marrow↗
PubMed1993

99Tcm-MDP global skeletal uptake and markers of bone metabolism in patients with bone diseases.

99Tcm-methylene diphosphonate (MDP) global skeletal uptake (4 h GSU) was determined by quantitative measurement of activity on bone scan images 4 h after injection in whole skeleton regions of interest (ROI) in 16 normal subjects, in five patients with hypertrophic pulmonary osteoarthropathy (HPO) and in 12 with Paget's disease. Values were correlated with those of whole body retention (24 h WBR), and serum bone gla protein (BGP), i.e. osteocalcin, alkaline phosphatase (AP) and type 1 procollagen (P1CP). They were 40% higher in HPO than in the normal controls, while in Paget's disease they increased more in polyostotic than in monostotic patients. A statistically significant difference was noted between 4 h GSU and 24 h WBR values in the two groups of patients compared with the controls. Of the bone metabolism markers, serum AP and P1CP were higher in the patients and positively correlated with their enhanced 4 h GSU values, whereas BGP was always within the normal range. This method may thus be regarded as a useful way of simultaneously determining bone 99Tcm-MDP uptake and altered bone turnover sites, especially in patients with systemic bone disease.

Adult↗
PubMed1993

Radioimmunoscintigraphy with 99mTc-225.28S-F(ab')2 in cutaneous and ocular melanomas: cases of particular clinical interest.

In the attempt to contribute to a correct and early diagnosis of melanoma, this paper critically evaluates, in 40 patients with cutaneous localization and 20 with ocular localization, the results of immunoscintigraphy with 99mTc-225.28S-F(ab')2 and the clinical, instrumental and biopsy findings. While the cutaneous melanoma group is mainly composed of patients subjected to surgical exeresis of the lesion before radioimmunoscintigraphy (RIS), the ocular melanoma group is composed of patients with the primary lesion in situ or previously treated with contact radiotherapy. In the cutaneous melanoma group 5 cases presented falsely positive immunoscintigraphic findings, and only 2 falsely negative. In the ocular melanomas, the percentage of false negatives was higher (n = 7). This is probably attributable to the antigenic expressivity, higher in the metastases than in the primary melanomas. The cases of particular interest are discussed in relation to the clinical picture, to the instrumental examinations and to the histological findings. The work made it possible to contribute to a more correct interpretation of the RIS findings in the staging and follow-up of cutaneous and ocular melanomas.

Adult↗
PubMed1993

Primary malignant melanoma arising in an ovarian dermoid cyst: proposed use of radioimmunoscintigraphy with 99mTc-F(ab')2 antimelanoma antibody for staging and follow-up. Case report.

A case of primary amelanotic ovarian malignant melanoma arising in a dermoid cyst is presented. Grossly, inside the cyst, pigmented solid lesions were not detected. Histologically, an area with undeniable malignant microscopic features was revealed and its melanomatous identity was confirmed by positive S-100 protein and melanoma antigen immunoreactivity. Recently, after 21 months from surgery this patient has also undergone radioimmunoscintigraphy (RIS) with 99mTc labelled antimelanomatous antibodies which revealed a possible secondary paracolic localization. Regardless of this evidence, although the patient has always refused chemotherapy and second look surgery for removal of the suspicious area, she is alive 1 year after surgery and now doing well. The authors also report the usefulness of employing the RIS technique in evaluating the metastatic spread in this type of malignancy.

Antibodies, Neoplasm↗
PubMed1992

A new method for assessing 99Tcm-MDP bone uptake from a bone scan image: quantitative measurement of radioactivity in global skeletal regions of interest.

Bone uptake of 99Tcm-MDP was evaluated 4 h after injection in 27 normal subjects aged 23-50 years by gamma camera measurement of the activity in whole skeleton regions of interest (ROIs) in anterior and posterior projection. The mean global skeletal uptake (GSU) (% of whole-body activity in both projections measured 30 s after injection) was 33.5 +/- 4%. The standard urinary excretion method (whole-body retention, WBR) gave a mean bone uptake value of 31.5 +/- 4%. A significant correlation (r = 0.570; P less than 0.002) was found between GSU and WBR. The mean bone-to-soft tissue ratio (B/S index) was 3.0 +/- 1.1. It is suggested that this direct, external counting method provides a way of obtaining both a qualitative and a semiquantitative evaluation of bone uptake with a single tracer administration in a routine bone scan. Investigation of its use in the assessment of bone involvement in low and high turnover bone diseases is now under way.

Adult↗
PubMed1989

[Bone metabolism in thalassemic children with multiple transfusions. Compartmental analysis of 99mTc-Sn-MDP kinetics].

The kinetics of 99mTc(Sn) methylene diphosphonate [99mTc(Sn)MDP] were evaluated by means of compartmental analysis in 5 normal children and 17 thalassemic subjects. Blood and urine activity were analyzed with a computer program which generates intercompartmental rate constants by an iterative least-square method providing a best-fit to the input data. The amount of tracer in each compartment (corrected for decay) was determined as a function of time. The transfer rate of 99mTc(Sn)MDP from blood to extracellular fluid and lamellar bone (K1-3) was about 20% higher in thalassemic subjects than in normal children. The transfer rate of 99mTc(Sn)MDP from blood to woven bone (K1-4) was about 57% higher in thalassemic subjects. A faster rate of spread into woven bone appears to be the major cause of higher bone uptake of 99mTc(Sn)MDP in thalassemic subjects, which suggests that in these patients bone tissue reoccupies the space previously replaced by hyperplastic marrow. Moreover, the increased bone extraction rate revealed a correlation between anemia and bone metabolic activity.

Adolescent↗
PubMed1989

Clearance kinetics and fate of macromolecular IgA in patients with IgA nephropathy.

IgA glomerulonephritis is associated with macromolecules of polymeric IgA in the circulation and mesangial deposits. An impairment in the reticulophagocytic function of patients with IgA nephropathy has been postulated as the potential cause for persistence of IgA immune complexes in the circulation and their eventual glomerular deposition. Since the fate and removal mechanisms of circulating macromolecular IgA are unknown in humans, we examined the blood clearance and organ uptake of purified IgA polymers and macromolecules in patients with IgA nephropathy and normal controls. The IgA macromolecules were prepared by covalent cross-linking of purified human polymeric IgA with a heterobifunctional reagent, N-succinimidyl 3-(2-pyridyldithio) propionate. After intravenous injection, large IgA molecules were removed rapidly from the circulation of patients (t1/2 = 3.8 +/- 1.0 minutes) and controls (t1/2 = 4.9 +/- 1.5 minutes). Dynamic gamma camera scintigraphy revealed the liver as the major organ that mediated the removal of the macromolecular IgA with no significant difference in the rate of hepatic uptake for patients (t1/2 = 3.4 +/- 0.6 minutes) and controls (t1/2 = 3.3 +/- 0.9 minutes). No significant amount of radioactivity could be detected in the lungs, kidneys, and spleen. The small polymers had a slower and similar clearance rates for patients (t1/2 = 29.3 +/- 7.9 h) and controls (t1/2 = 29.0 +/- 8.6 h). These findings have general significance in showing the liver as a major organ for removal of macromolecular IgA. In addition, the results have specific importance in showing that patients with IgA nephropathy do not suffer from an IgA removal dysfunction.

Adolescent↗