Late relapse after autologous BMT.
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Biomedical subjects
Publications and source records attributed to M Tommasi.
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Using the new Bayer H*3 hematology analyzer (Leverkusen, Germany), we have determined red blood cell and reticulocyte indices in 64 healthy subjects, in patients with microcytosis due to iron deficiency (58 patients) and heterozygous beta-thalassemia (40 patients), and in patients with macrocytosis (28 patients). We found in all cases that reticulocytes were larger than mature red cells by 24% to 35%, with a hemoglobin concentration 16% to 25% lower and a similar hemoglobin content. The correlation between red cell and reticulocyte indices was strikingly tight (r = .928 for volume, r = .929 for hemoglobin concentration, r = .972 for hemoglobin content) in all four groups, regardless of red blood cell size. The ratio of reticulocyte to red blood cell mean corpuscolar volume (MCV ratio) was constantly above 1. Inversion of the MCV ratio was observed only in four patients. It was always abrupt and transitory and was associated with erythropoietic changes leading to the production of red blood cells of a different volume (treatment of megaloblastic anemia, functional iron deficiency, bone marrow transplantation). In two cases of marrow transplantation, reticulocyte volume fell during the aplastic phase after conditioning chemotherapy and then rapidly increased up to values higher than before; this production of macroreticulocytes was the earliest sign of engraftment.
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The effect of rIL-12 on induction of CD69 antigen expression and cytolytic activity in purified human NK cells was evaluated in comparison to the effects of rIL-2 and rIFN-alpha. It was found that rIL-12 directly induced CD69 antigen expression in NK cells, although the period of incubation required by rIL-12 was longer than the period required by rIL-2 or by rIFN-alpha. Similarly, the cytolytic activity induced by rIL-12 in NK cells against the NK-resistant target cell line Raji was consistently lower than the cytolytic activity induced by rIL-2 or rIFN-alpha when measured after 6 hr of incubation, and increased during the following 18 hr of incubation. To compare the involvement of tyrosin kinases in activation of NK cells induced by rIL-2, rIL-12, and rIFN-alpha, the effect of the specific inhibitor of tyrosin kinases, genistein, was evaluated on induction of CD69 antigen expression and lytic function mediated by the three cytokines. It was found that genistein inhibited CD69 antigen expression induced by rIL-2 and by rIL-12, but not that induced by rIFN-alpha. Unlike the effect on CD69 antigen expression, the cytolytic activity induced by all three cytokines was inhibited by genistein. These results, together with the finding that CD69 antigen expression induced by rIL-2 but not by rIL-12 or rIFN-alpha was inhibited by addition of rIL-4, strongly suggest that IL-2, IL-12, and IFN-alpha mediate their effects, leading to induction of CD69 antigen expression through different activation pathways.
The serum tissue polypeptide antigen (TPA) was determined before and at the end of radiotherapy in a group of patients with head and neck epidermoid carcinoma. The baseline values were significantly higher than those in healthy control subjects. They did not depend on the site of the neoplasia but increased with clinical stage. A cut-off value of 85 U/l discriminated two groups of patients according to survival: patients whose values were lower than the cut-off had a disease-free 6-year survival rate of 61%, compared to only 22% in patients with higher TPA levels. Until the second year of follow-up, patients with complete response had baseline values significantly lower than relapsed patients. However, at 5 years the pretreatment values were similar for patients being disease-free, patients with recurrence and patients deceased within the 2-5 year period.
A twenty-five year old woman developed a progressive right hemiparesis which remitted within three months, without treatment. The diagnosis was a first relapse of multiple sclerosis. After a 10 year fully asymptomatic period, the patient developed weakness of the legs with falls and swallowing difficulties. Fasciculations and amyotrophy were present in the limbs and the tongue. There were no sensory abnormalities. The electromyogram confirmed the peripheral neurogenic degeneration with signs of anterior horn involvement. Motor and sensory nerve conductions were normal. Muscle weakness and atrophy increased in the limbs and the bulbar territory and the patient died nine months later. The autopsy showed characteristic "old" plaques of multiple sclerosis in the cerebrum with anterior horn cell and pyramidal tracts degeneration, typical of amyotrophic lateral sclerosis, in the spinal cord. Although exceptional, this association of amyotrophic lateral sclerosis and multiple sclerosis leads to the discussion of an etiological immunological dysregulation common to these two diseases.
The measurement of human 25-hydroxyvitamin D (25-OH-D) serum levels has a potential role in evaluating calcium and bone metabolism disorders. To determine normal ranges were studied, cross-sectionally, a healthy population of men and women, aged 18-69 years, over a 12-month period. Changes in 25-OH-D levels for the examined population fitted a mathematical model that demonstrated a highly significant periodic relationship to time. Gender had a significant (p < 0.03) effect on mean 25-OH-D concentration, but age was not significantly correlated with 25-OH-D in either sex. A 95% tolerance band was computed in order to have a time-qualified "range of normality" with circannual periodicity. Interesting periodic variations were seen for the parathyroid hormone (PTH) as well as for osteocalcin (OST). A moderate negative correlation was found between 25-OH-D and PTH in both sexes, with more significant evidence in males. No relationship was observed between 25-OH-D and OST.
The non-mitogenic stimulation of human peripheral blood mononuclear cells (PBMC) with low concentrations of the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) caused a progressive increase in the percent fraction of the cells that were positive for the early activating antigen CD69. At the same time, it caused a progressive increase in the steady-state levels of poly(ADP-ribose) polymerase (pADPRP) transcripts. A further increase in TPA concentration, while inducing the maximal expression of the levels of CD69 activating surface antigen, both in the presence or in the absence of proliferative activity, did not evoke any additional hightening of pADPRP mRNA levels. Time course of PBMC stimulation with a non-mitogenic dose of TPA showed an early increase in the accumulation of pADPRP mRNA, which changed at 8-16 h, and remained high for several days thereafter. On the basis of these data, we suggest that the increase in pADPRP mRNA may be associated with the commitment of human lymphocytes from a quiescent (G0) to an activated (G1) state.
The effect of rIL-4 on CD69 antigen expression induced by rIL-2 or by rINF-alpha on human resting NK cells and CD3+, CD4-, CD8- T lymphocytes has been investigated. rIL-4 drastically inhibited CD69 antigen expression induced by rIL-2 in both cell types. In contrast, rIL-4 did not alter rINF-alpha-induced CD69 antigen expression. Consistent results were obtained evaluating the cytolytic activity of NK cells against the Raji target cell line: rINF-alpha-induced lytic activity was not inhibited by rIL-4, while rIL-2-induced lytic activity was drastically inhibited. Proliferative activity of NK cells induced by rIL-2, in contrast, was only slightly reduced by rIL-4. rIL-4 did not alter the expression of the beta chain of IL-2 receptor, evaluated in NK cells by indirect immunofluorescence. Expression of the alpha chain of IL-2 receptor could not be detected in NK cells by indirect immunofluorescence. It can therefore be suggested that the selective inhibitory effect of rIL-4 on rIL-2-induced activation of NK cells is not mediated by downregulation of alpha and beta chains of IL-2 receptor.
From May 1988 to March 1990, 17 consecutive patients with histologically proven malignant mesothelioma were treated with epirubicin 75 mg/sqm i.v. on day 1 and ifosfamide 1.8 gr/sqm/day i.v. from day 1-5. Treatment was repeated every 3 weeks until progression. Fifty-three chemotherapy cycles were administered to the 17 patients treated (median, 3 cycles/patient). No complete responses, 1 partial response, 8 stable diseases and 8 progressions were noted. Toxocity was acceptable and no treatment-related deaths occurred. Actuarial median survival was 6 months. In this study, a combination of full doses of epirubicin and ifosfamide did not prove to be active in malignant mesothelioma.
The pathological process and lesion topography in patients with the syndrome of progressive aphasia are heterogeneous and few necropsy examination cases have been investigated. This is a case report of a 53 year old right handed man with progressive anarthria and secondary Parkinsonism over a period of six years. Positron emission tomography (PET) showed a decreased cerebral blood flow and metabolism in the frontal cortex, which was more pronounced on the left. Neuropathology disclosed a spongiform vacuolation in layer II of the frontal cortex, mostly in the Broca area, and neuronal loss in the substantia nigra. This original case reinforces the view that there are different entities of the syndrome of progressive aphasia which can be identified on the basis of clinical, neuroimaging and anatomical data.
A 34-year old right-handed man was suffering from recurrent cerebro-vascular insults. CT-scans revealed several subcortical lacunar infarcts, and leukoaraïosis. Arteriography of the left and the right carotid arteries was performed respectively on the 4th and the 9th year of the disease, and did not elicit significant extracranial and intracranial vascular lesions. There were no arguments in favor of infectious, inflammatory, or auto-immune vascular diseases. The patient had tardive hypertension and dementia, and died at the age of 44. Pathological findings, limited to the brain and cervical spinal cord, revealed numerous ischemic lacunar infarcts. Histological lesions were consistent with the diagnosis of arteriosclerotic leukoencephalopathy. There were oedema, palor, and loss of myelin in the white matter, and nonspecific diffuse arteriosclerotic lesions that were particularly pronounced in the intimal part of the arterial wall. No inflammatory process nor amyloid deposits were found. Despite the onset of the disease in a young adult and the late occurrence of hypertension, our case report shares most of the pathological features of the Binswanger's type of arteriosclerotic encephalopathy.
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From September 1986 to April 1988, all consecutive patients with histologically proven (pathologic review mandatory) malignant mesothelioma, measurable disease, age less than 75 years, Karnofsky performance status equal to or greater than 40, and no previous chemotherapy were treated with epirubicin at the dosage of 75 mg/m2 i.v. every 3 weeks. Of the 23 patients who entered the study, 2 were retrospectively found not to have malignant mesothelioma. In the 21 eligible patients (all evaluable), no complete remission, 1 partial remission, 11 stable diseases and 9 progressions were noted. Toxicity was very mild. Median survival was 7.5 months. At the dosage used, epirubicin proved to be of little value in the management of these patients. Whether higher doses are more effective, as has been noted in other tumors, remains to be ascertained.
We report here a post-mortem examination of a 46-year-old patient who died after a 23-year-long syringomyelia-like syndrome of Tangier disease. The L5 dorsal root and the superficial peroneal nerve showed fiber loss and lipid vacuole accumulation in Schwann cell cytoplasm. The L5 ventral root had moderate fiber loss without lipid vacuoles. In the cervical roots, fiber loss was intense and there were no foamy Schwann cells. Motor neuron loss was severe in the cervical spinal cord and the facial nerve nucleus and slight at the lumbar level. Under electron microscopy, some neurons of the lower spinal cord showed atypical inclusions. These data suggest that an unknown metabolic defect is responsible for a primary neuronopathy. Lipid accumulation in Schwann cells, resulting from fiber degeneration is probably transient, accounting for the absence of foamy cells in regions with longstanding involvement.
We searched for Epstein-Barr virus (EBV) sequences by enzymatic DNA amplification in nine primary brain lymphomas from patients without immunodeficiency. We used seven nonlymphoma brain tumors as negative controls, and the Raji cell line as a positive control. We detected EBV DNA, using ethidium bromide-stained-agarose minigel electrophoresis and dot blot hybridization, in the positive control and in only one brain lymphoma tumor; we did not detect EBV DNA in the other tumors. The EBV-positive patient had a second B-cell monoclonal population in the peripheral blood without detectable EBV DNA, suggesting a direct role for EBV in the development of the brain lymphoma.
The hitherto conventional classification of primitive brain tumours has been recently, and somewhat tentatively, revised for pediatric pathology: a new class of tumours, named Primitive Neuroectodermal Tumours (PNET) has been established, encompassing many undifferentiated, small cell tumours of uncertain origin, mainly medulloblastomas. This paper deals with these concepts, and with some practical and/or theoretical problems mainly concerning childhood lobrastrocytomas, medulloblastomas and ependymomas, regarding the role of pathology in their diagnosis and prognosis.