Biomedical subjects
P Tomasi
Publications and source records attributed to P Tomasi.
Thyrotropin concentration in hypopituitarism.
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Spontaneous nocturnal growth hormone secretion in anorexia nervosa.
In anorexia nervosa, serum GH levels are increased under basal conditions and respond abnormally to provocative stimuli. We report here, for the first time, an analysis of pulsatile GH secretion in these patients performed by Cluster algorithm. Seven anorectic and six normal weight, healthy women underwent serial blood sampling at 20-min intervals form 2030-0830 h for GH estimation. The total area under the curve (AUC; micrograms per L/min) was elevated 4-fold in anorectic patients compared to controls (4743.0 +/- 1520.09 vs. 1148.6 +/- 519.27; P < 0.01), largely due to an increase in the non-pulsatile fraction (3212.5 +/- 990.45 vs. 378.7 +/- 123.27; P < 0.01). Accordingly, the valley mean value was higher in anorectic than in control subjects (5.9 +/- 2.25 vs. 1.0 +/- 1.30 micrograms/L; P < 0.01). Furthermore, pulsatile AUC was also greater in anorectic patients (1530.4 +/- 654.72 vs. 769.8 +/- 404.02; P < 0.01) due to a significant increase in GH peak frequency (5.0 +/- 0.81 vs. 3.0 +/- 0.89; P < 0.01). No correlations were observed in these patients between body mass index and any of the parameters of spontaneous GH release, whereas a positive correlation was found between insulin-like growth factor I levels and pulsatile AUC (r2 = 0.583; P < 0.05), peak height (r2 = 0.743; P = 0.01), peak increment (r2 = 0.801; P < 0.01), and GH valley mean (r2 = 0.576; P < 0.05). In conclusion, it appears that the enhanced GH secretion in anorexia nervosa is the result of an increased frequency of secretory pulses superimposed on enhanced tonic GH secretion. Although this latter is consistent with a reduction of hypothalamic SRIH tone, the former may be accounted for by an increased number of GHRH discharges. Considering that in normal weight and obese subjects parameters of GH release are negatively correlated with adiposity indexes, the lack of such a negative correlation in our patients suggests that the enhancement of spontaneous GH release in anorectic patients is not merely the consequence of malnutrition-dependent impairment of insulin-like growth factor I production, but reflects a more complex hypothalamic dysregulation of GH release.
Pulsatile secretion of thyrotropin in children.
To examine pulsatile TSH secretion, serum TSH was determined every 30 min for 24 h in eight short normal prepubertal children (3 males and 5 females, age 4.0-12.6 yr). All children exhibited a clear circadian pattern of TSH secretion. Pulsatile TSH secretion was identified in all subjects with a mean (+/- SD) TSH pulse frequency of 6.9 +/- 1.2 pulses/24 h. The group mean TSH pulse amplitude was 1.4 +/- 0.3 mU/L. Mean TSH concentration was higher during the night hours (2.1 +/- 0.8 mU/L) than during the day hours (1.3 +/- 0.4 mU/L, p < 0.005), and significantly more pulses were detected during the night (mean 4.7 +/- 1.4) than during the day hours (2.1 +/- 0.6, p < 0.005). On average, 62 to 68% of the peaks were detected in the night hours. Mean TSH pulse amplitude during the night hours was not significantly different from that during the day hours. Our findings indicate that, as previously shown in adults, a pulsatile pattern of TSH secretion is present in children. In our study group, the nocturnal TSH surge is associated with an increase in pulse frequency but not amplitude.
Acute promyelocytic leukemia: morphological aspects.
Among AML with maturation, acute promyelocytic leukemia (APL) represents a distinct subtype which accounts for 5-10% of all the FAB variants. APL may be recognized by different cytological pictures: (i) Hypergranular APL, the most typical form, showing promyelocytes with cytoplasm packed with purple granules. Most of the primary granules may be incorporated into Auer rods, sometimes stacked in bundles of faggots. (ii) Microgranular APL, characterized by fine dust-like granulation in the cytoplasm; some promyelocytes may even appear agranular by light microscopy. Most of the cells show bilobed or folded nuclei, a picture which may simulate that of acute myelomonocytic leukemia. (iii) Hyperbasophilic form, characterized by cells with high N/C ratio, and strongly basophilic cytoplasm with either sparse or no granules. Conspicuous cytoplasmatic budding is usually present, recalling the feature of micromegakaryocytes. Strong positivity for myeloperoxidase, Sudan black B and chloroacetate esterase represents the typical cytochemical pattern of M3; usually a weaker reactivity may be observed in M3v. However, sometimes a degree of cytochemical heterogeneity of APL cells may be observed, as suggested by cases displaying a strong sodium fluoride-sensitive nonspecific esterase reaction. Recently a distinct entity associated with basophilic differentiation has been described. Differential diagnosis of this form with M2-baso subtype and with cases of MDS or AML with basophilia (M2, M4 with t(6;9) translocation) may be obtained by the use of cytochemistry, cytogenetic investigations, and electron microscopy.
Acute promyelocytic leukemia: morphological aspects.
Among AML with maturation, acute promyelocytic leukemia (APL) represents a distinct subtype which accounts for 5-10% of all the FAB variants. APL may be recognized by different cytological pictures: (i) Hypergranular APL, the most typical form, showing promyelocytes with cytoplasm packed with purple granules. Most of the primary granules may be incorporated into Auer rods, sometimes stacked in bundles of faggots. (ii) Microgranular APL, characterized by fine dustlike granulation in the cytoplasm; some promyelocytes may even appear agranular by light microscopy. Most of the cells show bilobed or folded nuclei, a picture which may simulate that of acute myelomonocytic leukemia. (iii) Hyperbasophilic form, characterized by cells with high N/C ratio, and strongly basophilic cytoplasm with either sparse or no granules. Conspicuous cytoplasmatic budding is usually present, recalling the feature of micromegakaryocytes. Strong positivity for myeloperoxidase, Sudan black B and chloroacetate esterase represents the typical cytochemical pattern of M3; usually a weaker reactivity may be observed in M3v. However, sometimes a degree of cytochemical heterogeneity of APL cells may be observed, as suggested by cases displaying a strong sodium fluoride-sensitive non-specific esterase reaction. Recently a distinct entity associated with basophilic differentiation has been described. Differential diagnosis of this form with M2-baso subtype and with cases of MDS or AML with basophilia (M2, M4 with t(6;9) translocation) may be obtained by the use of cytochemistry, cytogenetic investigations, and electron microscopy.
Experience with the multichannel intracochlear nucleus mini device in 24 postlingually deaf patients.
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Distinct cytogenetic and clinicopathologic features in acute myeloid leukemia after occupational exposure to pesticides and organic solvents.
BACKGROUND: To study the correlation of environmental exposure to potentially mutagenic agents and the clinicopathologic picture in acute myeloid leukemia (AML), clinical features, morphologic characteristics, immunophenotype, and cytogenetics were studied in 59 patients with newly diagnosed AML. METHODS: Based on interviews on occupational hazards and hobbies showing prolonged contact with pesticides (18 patients) and organic solvents (7 patients), 25 patients were categorized as "exposed". Thirty-four patients were categorized as "unexposed,", based on anamnestic findings. RESULTS: Light microscopic studies showed myelodysplasia involving multiple cell lineages in all assessable patients with professional exposure to pesticides and organic solvents, whereas morphologic aberrations of the non-blast cell population were confined to a minority of cells in unexposed patients. These findings were confirmed by electron microscopic studies in 31 patients. Immunologic analysis showed the presence of a minor megakaryoblastic component in six exposed patients and showed positive findings for the CD34 stem cell marker in 85% of exposed patients, a figure significantly higher as compared with that for unexposed subjects. Cytogenetic studies confirmed the frequent occurrence of 5q and/or 7q aberrations in patients occupationally exposed (10 of 25 cases). Other recurring chromosome aberrations in the exposed group were 17p-, trisomy 11q, and translocation of 16q, 6p, 7p, and 11p, whereas the classic AML-specific translocations (i.e., t[15;17]; t[8;21]) were detected only in unexposed subjects. Conventional chemotherapy achieved complete remission in 1 of 19 exposed patients, as opposed to 14 of 29 unexposed patients, with a median survival of 2 months in the former group and 8 months in the latter. CONCLUSIONS: Taken together, these findings document that AML in patients professionally exposed to toxic substances may represent a distinct cytogenetic and clinicopathologic entity. The clinicobiologic characteristics in these exposed patients are similar to the features of AML arising in patients with prior chemotherapy for another tumor, thus suggesting that similar transformation pathways may underlie leukemogenesis induced by cytotoxic drugs and by environmental exposure to some pesticides or organic solvents.
Diagnosis of leukemia: morphology.
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Anti-A autoantibody associated with immune hemolytic anemia.
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Adrenergic stimulation of the human pituitary-adrenal axis is attenuated by an analog of met-enkephalin.
It has previously been suggested that endogenous opioid peptides may suppress the pituitary-adrenal axis in man by inhibiting an excitatory alpha 1-adrenoceptor input to neural mechanisms liberating corticotrophin-releasing factor or factors (CRFs). This hypothesis has been tested here by investigating the effect of the met-enkephalin analog, DAMME (FK-33,824), on the elevation in serum cortisol induced by the catecholamine-releasing agent d-amphetamine (10 and 25 mg p.o.) and the direct alpha 1-adrenoceptor agonist methoxamine (6 micrograms/kg/min i.v.) in two groups of 6 normal male subjects. In both studies, the rise in serum cortisol was significantly attenuated by the analog of met-enkephalin. These data suggest that exogenous opioids act as a site downstream to the alpha 1-adrenoceptor input to CRF release; it appears that opioids modulate adrenocorticotrophic hormone release in man at a minimum of two distinct and separate sites.
Giant cell tumor of bone: a model for the in vitro human osteoclast characterization.
The in vitro growth pattern of cells obtained from bioptic material of ten patients with giant cell tumor of bone (GCT) was investigated. Cytochemical reactions and monoclonal antibodies raised against macrophage markers were tested on the two histologically identifiable GCT cell populations. Only monoclonal antibody EBM/11 stained both mononuclear and giant cells. EBM/11 positivity and resistance of acid phosphatase to high doses of tartrate strongly suggest that both mononuclear and giant cells belong to the same lineage.
Cytogenetic analysis of different cellular populations in chronic myelomonocytic leukemia.
Karyotypes of different cellular populations made after separation of bone marrow cells on a gradient of Percoll were evaluated in seven patients affected by chronic myelomonocytic leukemia diagnosed according to FAB criteria. Megakaryocytes, monocytic cells, and granulocytic and erythroid precursors were preferentially collected after centrifugation between density layers of 1045-1050 mg/ml, 1050-1060 mg/ml, and 1065-1070 mg/ml, respectively. The enriched cell fractions were cultured separately and submitted to cytogenetic investigation after short-term culture. Some chromosome aberrations (5q-,+8) were observed in all cellular fractions in three patients, thus providing cytogenetic evidence of the involvement of a common progenitor stem cell in this myelodysplastic disorder. On the other hand, chromosome abnormalities such as del(3)(q21) and del(11)(q23) appeared to be confined to the megakaryocytic and the monocytic fractions, respectively, in two patients. It is conceivable that lineage-restricted aberrations may develop as a consequence of a multistep clonal evolution and may show a close relationship with the hemopoietic differentiative processes.
[Cytogenetics of the malignant hemopathies: cyto-biological correlations and clinical implications].
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Cytology of chronic lymphocytic leukemias.
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Serum beta 2-microglobulin in malignant lymphoproliferative disorders.
Beta 2-microglobulin (B2m) was measured on serum samples in 274 patients with acute and chronic lymphoproliferative disorders (85 non-Hodgkin lymphomas-NHL, 30 Hodgkin lymphomas-HL, 34 B-cell chronic lymphocytic leukemias-B-CLL, 8 Waldenström macroglobulinemias-WM, 76 multiple myelomas-MM, 31 acute lymphoblastic leukemias-ALL, 10 hairy cell leukemias-HCL). Two hundred and four patients were studied at the time of diagnosis, and results were correlated to clinical stage, and histologic subtype in NHL, immunoglobulin type in MM, and immunologic phenotype in ALL. Moreover, B2m was tested during and after chemo- and/or radiotherapy, and results were correlated to response, progression or relapse. Elevated pretreatment B2m values were found in widespread forms of NHL and HL, in patients with B symptoms and in the unfavorable histologic subgroups of NHL. Rapid falls in levels followed therapy institution. In B-CLL and in MM a close relationship between B2m and cell mass was found. A significant B2m level reduction followed treatment, whereas its increase could detect a relapse. In ALL, serum B2m was only slightly above the normal range. B2m seems to reflect the total burden of malignant cells mainly in MM and B-CLL; in other lymphoproliferative disorders it provides less prognostic information.
Significance and limits of cerebrospinal fluid beta-2-microglobulin measurement in course of acute lymphoblastic leukemia.
Cerebrospinal fluid beta-2-microglobulin (CSF-beta 2m) was measured longitudinally in 48 patients affected by acute lymphoblastic leukemia (ALL). Thirteen developed a central nervous system (CNS) involvement during the course of the disease; although moderately higher mean CSF-beta 2m levels were found in these subjects, no significant statistical differences were observed in comparison with patients without this complication and compared with the control group. No correlations were found between beta 2m and other biochemical parameters in CSF. Furthermore, CSF-beta 2m levels appeared to be influenced by previous combined chemoradiotherapeutic treatment for CNS prophylaxis, presence of meningeal non-neoplastic infiltrates, patients' ages, amount of CSF blasts, and their immunological phenotype. In particular, only clearly B-committed leukemic cells, when tested, showed a strong surface expression of beta 2m, as demonstrated by immunocytochemical detection of this protein on cell membrane. However, in specific cases, CSF beta 2m measurement and CSF/serum beta 2m ratio were helpful in diagnosing and monitoring isolated CNS disease. Such findings suggest that CSF-beta 2m assay may be a useful tool in the management of CNS involvement in the course of ALL in only selected patients, as several factors can modify the outcome.
Neuroendocrine regulation of human growth hormone secretion. Diagnostic and clinical applications.
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