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Biomedical subjects

A Proia

Publications and source records attributed to A Proia.

At least 19 recordsLinked to original sources
PubMed2002

Thrombotic thrombocytopenic purpura and pregnancy: a case report and a review of the literature.

Thrombotic thrombocytopenic purpura (TTP) is a severe disorder affecting the microcirculation of multiple organ systems. Plasma therapy has significantly reduced the mortality rate. Infections, pregnancy, cancers, drugs, and surgery were frequently associated with the initial episodes and relapses. Women who are either pregnant or in the postpartum period make up 10-25% of TTP patients, suggesting the interrelationship between TTP and pregnancy. The introduction of aggressive treatment with plasma transfusion or plasmapheresis improved maternal and fetal survival rates. We describe a case of a first successful pregnancy concomitant to a late relapse of TTP, in which the identification of important risk factors for both TTP and pregnancy allowed us easier hematological and obstetrical management. Proposed guidelines for pregnancy-related TTP management and a brief review of current treatment options for this rare condition are also included.

Adult↗
PubMed2001

Obesity and autologous stem cell transplantation in acute myeloid leukemia.

In the bone marrow transplant setting, several authors hypothesized that severely overweight patients are at increased risk of transplant-related toxicity, but different definitions of obesity, different body weight groupings and heterogeneous samples of patients were analyzed. To overcome these limitations, we retrospectively considered a homogeneous group of 54 patients (median age 36.5 years), with a diagnosis of de novo acute myeloid leukemia (AML), autografted in first complete remission (CR) with the Bu-Cy2 conditioning regimen, dosed on actual body weight. Patients were classified into three groups (obese, non-obese, underweight) using body mass index (BMI = kg/m(2)); for each group we analyzed transplant-related toxicity and mortality, overall survival and disease-free survival (OS/DFS). In spite of the relatively small number of patients, in our results high BMI appears a predictive factor for an increase of treatment-related toxicity and mortality. Moreover, 30 (55%) patients are currently alive in continuous CR, and after a median follow-up of 76.5 months (range 14-137) statistically significant differences in OS and DFS were detected between obese and non-obese groups (P = 0.012 and 0.021, respectively). Our study suggests that obesity may represent an independent risk factor for autograft in AML and further investigations are warranted.

Adult↗
PubMed2001

Thrombotic thrombocytopenic purpura: prospective neurologic, neuroimaging and neurophysiologic evaluation.

BACKGROUND AND OBJECTIVES: Neurologic symptoms are present in 60% of patients with thrombotic thrombocytopenic purpura (TTP) on initial examination and ultimately develop in about 90% of cases during the course of the disease. Despite central nervous system involvement being frequent, abnormalities in the brain of patients with TTP are infrequent on neuroimaging (CT/MRI) and neurophysiologic (EEG) evaluation, often reversible and mainly limited to symptomatic stages of the disease. The aim of our study was to establish the value of a complete neurologic screening as part of the work up of TTP. DESIGN AND METHODS: We prospectively evaluated 16 TTP patients, performing serial neurologic, neuroimaging and EEG examinations, independently of the presence of an objective central nervous system involvement. RESULTS: Our study shows that a complete neurologic evaluation is of modest help in improving the diagnosis of TTP, but may be useful for the neurologic management. INTERPRETATION AND CONCLUSIONS: Accurate neuroimaging and, especially, EEG evaluation and monitoring allowed us to identify patients who could benefit from anticonvulsive therapy, avoiding the unnecessary administration of the latter. The prognostic utility of complete neurologic screening in TTP remains to be conclusively demonstrated in larger prospective neurologic studies.

Adolescent↗
PubMed2000

Conventional salvage chemotherapy vs. high-dose therapy with autografting for recurrent or refractory Hodgkin's disease patients.

Despite progress that has been made in curing Hodgkin's disease (HD), patients whose first remission is brief and those resistant to first-line chemotherapy still have a poor outcome. We retrospectively reviewed data from 29 patients with HD in first relapse or refractory to first-line chemotherapy. Following failure, all patients received three cycles of ifosfomide, epirubicin, and etoposide (IEV); moreover, 11 patients received a conditioning regimen followed by autografting. Of the 18 patients treated with IEV, eight (44%) are alive; nine died of disease progression, and one died of hematologic toxicity. The 24-month overall survival (OS), relapse-free survival (RFS), and event-free survival (EFS) are 18%, 44%, and 22%, respectively. Of the 11 patients treated with IEV and autografting, ten are alive (90%) and one patient died of progressive disease. The 29-month OS, RFS, and EFS are 91%, 71%, and 56%, respectively. Our results confirm data showing that patients with relapsed or resistant HD achieve a significantly better OS and EFS if treated with high-dose therapy and autografting.

Adult↗
PubMed2000

Acute myeloid leukemia and lung cancer occurring in a chronic lymphocytic leukemia patient treated with fludarabine and autologous peripheral blood stem-cell transplantation.

An increased incidence of different malignancies associated to chronic lymphocytic leukemia (CLL) has been reported. The association of CLL and acute leukemia is a rare event described in < 1% of CLL, the type of acute leukemia being either from the lymphoid or more often from the myeloid lineage. The coexistence of acute myeloid leukemia (AML) and CLL in the same patient has been occasionally reported. Most of these cases have been associated with the administration of chemotherapy or radiotherapy for CLL, suggesting that the former may be a secondary leukemia. On the other hand, CLL could precede, but could also be diagnosed at the same, or delayed time as AML, suggesting the presence of other leukemogenic factors. We describe the exceptional development of AML and lung cancer in a patient with previously diagnosed CLL in minimal residual disease status after fludarabine treatment followed by autologous peripheral blood stem-cell transplantation.

Acute Disease↗
PubMed2000

Unmanipulated peripheral blood stem cell autograft in chronic lymphocytic leukemia: clinical findings and biological monitoring.

BACKGROUND AND OBJECTIVES: To investigate the feasibility of peripheral blood stem cell (PBSC) transplantion in patients with high-risk chronic lymphocytic leukemia (CLL) in remission after fludarabine therapy, the clinical impact of minimal residual disease (MRD) monitoring and the immunologic reconstitution after transplantation. DESIGN AND METHODS: Twenty CLL patients, in clinical complete remission (CR) after fludarabine, were offered an unmanipulated PBSC transplant and were longitudinally monitored for MRD and immunologic reconstitution. RESULTS: Due to unsatisfactory PBSC collection, 4 patients received bone marrow cells. All patients engrafted. Two patients died, one due to infection and one because of another neoplasia. Thirteen patients are at present in clinical CR after a median follow-up of 17 months and 18 patients are alive with a survival probability of 0.87 (+/-0.04) at 52 months after transplant. Fifteen patients had a molecular remission. Three of them showed a molecular relapse 16-28 months after autograft, followed by a clinical relapse 10-16 months later. Three of the four patients who remained persistently rearranged could be revaluated over time and showed an immunologic relapse 11-26 months after transplant; two of these had a clinical relapse 12 and 7 months later. A marked and persistent impairment of both the B- and T-immunologic compartments was recorded in the horizontal follow-up. INTERPRETATION AND CONCLUSIONS: Unmanipulated PBSC autograft is a feasible procedure that produces prolonged molecular remissions in high-risk CLL patients. Persistence or reappearance of a molecular signal after engraftment is predictive of subsequent immunologic and clinical CLL recurrence. The long -lasting impairment of the host immune repertoire after fludarabine followed by autograft has to be taken into account in the patients' management.

Adult↗
PubMed1998

Rate of vascularization of coralline hydroxyapatite spherical implants pretreated with saline/gentamicin, rTGF-beta 2, and autogenous plasma.

Several authors have reported significant exposure rates using the hydroxyapatite orbital implant in the treatment of the anophthalmic socket. Histologic studies by ourselves and others have suggested that lack of fibrovascular ingrowth into the implants may contribute to conjunctival breakdown and exposure. Recently, much attention has been given to angiogenic factors, such as rTGF-beta 2 and those found in plasma, in accelerating wound healing and fibrovascular ingrowth. This pilot study compares the rate of vascularization of hydroxyapatite orbital implants pretreated with plasma, rTGF-beta 2, and a saline/gentamicin solution with that in untreated controls ina population of New Zealand albino rabbits. Hydroxyapatite orbital spheres were implanted subcutaneously and in enucleated orbits. Untreated implants were used as a control. Implants pretreated with plasma, rTGF-beta 2, and a saline/gentamicin solution were removed and examined histologically at weekly intervals for the first 3 weeks after implantation. Histologic studies demonstrated that the rate of vascularization significantly increased between 2 and 3 weeks postoperatively in all study groups. Pretreating the implants with rTGF-beta 2 in phosphate buffered solution (PBS) or autogenous plasma did not significantly increase the rate of vascularization in comparison with controls at weeks 1 and 2. However, pretreating the implants with a saline/gentamicin solution or PBS alone was associated with an increased rate of vascularization at weeks 2 and 3. No statistically significant difference in vascularization was noted between the subcutaneous and orbital implants at any week. Hydroxyapatite implants pretreated with saline/gentamicin or phosphate buffered solutions underwent more rapid vascularization at weeks 2 and 3 in comparison with controls. Additionally, all groups were noted to have a more rapid rate of ingrowth between weeks 2 and 3 than between weeks 1 and 2. Plasma and rTGF-beta 2 (at the dose used) did not significantly alter the rate of vascularization of hydroxyapatite implants during the first 2 to 3 weeks. The significance of these findings is discussed.

Animals↗
PubMed1998

Chronic lymphocytic leukemia: from palliative therapy to curative intent.

High dose therapy and stem cell transplantation is increasingly being used for treatment of CLL. The present article summarizes available results reported in literature on the use of high dose therapy followed by allogeneic or autologous hemopoietic precursor infusion. Transplant procedures seem a feasible approach, especially autografts, while allogeneic transplant has been associated with a higher mortality rate. Interesting clinical/biological results have been reported for both allogeneic and autologous transplants but prospective large clinical trials are needed to establish their real value. We consider important issues of stem cell transplantation in CLL patients, such as the kind of transplant (allogeneic vs autologous), the optimum timing, the selection of patients, the value and type of purging and, above all, impact on survival.

Bone Marrow Transplantation↗
PubMed1996

Meningeal localization in a patient with Hodgkin's disease. Description of a case and review of the literature.

We report the case of a 21-year-old man in whom intracranial localization was discovered during initial staging at the onset of Hodgkin's disease (HD). The patient was treated by surgical excision, irradiation and chemotherapy and 50 months after completion of therapy is in remission with no evidence of HD. A brief review of the literature regarding 48 patients with intracranial Hodgkin's disease is presented.

Adult↗
PubMed1996

Autologous bone marrow transplantation in 44 patients with aggressive non-Hodgkin's lymphoma at University "La Sapienza" of Rome.

High dose therapy followed by infusion of autologous bone marrow has become a major treatment option for an increasing number of poor prognosis non-Hodgkin's lymphoma (NHL) patients. In our study we analyzed the outcome of autologous bone marrow transplantation (ABMT) in 44 high grade NHL patients transplanted at our institution between 1985 and 1992. Median age was 31 years (range 12-61); nineteen were in partial remission (PR) after first line chemotherapy and 25 in sensitive relapse (SR). Of the 25 patients transplanted in SR, 14 relapsed after a median time of 5.5 months (range 1-26), 8 are in complete remission after a median follow up of 41.5 months and three died from toxicity. Of the 19 patients grafted in PR, 11 are alive and progression free after a median follow up of 52 months, while 8 relapsed at a median time of 5 months. The overall progression free survival (PFS) projected at 6 years is 35% with a 47% PFS for patients transplanted in PR and 28% for patients in SR. In conclusion, high dose therapy and ABMT has achieved widespread use as salvage therapy for patients with relapsed/refractory high grade NHL. In particular, our experience confirms that myeloablative treatment is a safe and well tolerated procedure for patients in PR, that may be easily applied as early salvage therapy without major toxicities.

Adolescent↗
PubMed1988

The functional role of the pedunculopontine nucleus in the regulation of the electrical activity of entopeduncular neurons in the rat.

The purpose of this study was to investigate the influence of the pedunculopontine nucleus (PPN) on the electrical activity of entopeduncular nucleus (EP) in the rat and to analyze the influence of the subthalamic nucleus (STN) on the PPN-evoked responses of EP cells. Most of the EP neurons recorded (65.1%) were identified electrophysiologically as output cells projecting to the lateral habenula while only a minority (3.8%) were output cells to the PPN. Stimulation of the PPN in intact rats caused a short-latency (2.5 +/- 2.0, S.D. ms) activation in 22.6% and suppression of activity in 8.5% of EP neurons recorded. The mean impulse rate of EP neurons in intact rats was 27.0 +/- 5.5, S.D. imp./s and the overall mean interspike interval 36.8 +/- 7.1, S.D. ms. In rats where the PPN had been destroyed 10-12 days before recording by a local microinjection of kainic acid only a few EP neurons were still responsive to stimulation of the PPN showing suppression of activity. In these rats the kainate lesion slowed the impulse spontaneous activity to 14.3 +/- 6.3, S.D. imp./s and markedly altered the distribution of interspike intervals in 62.5% of the EP neurons recorded. The overall mean interspike interval in this group of deregulated neurons was 68.2 +/- 20.1, S.D. ms. A small kainate lesion of the STN placed 4-5 days before recording, on the other hand, did not affect the spontaneous activity of EP cells but increased the percentage of cells which were activated (43.6%) by stimulating the PPN. The present data demonstrate a predominant activatory influence of the PPN on EP cells and suggest that destruction of the STN may affect the responsiveness of entopeduncular cells to stimulation of the PPN possibly through the removal of a tonic inhibitory STN influence on the EP.

Action Potentials↗
PubMed1987

The reciprocal electrophysiological influence between the nucleus tegmenti pedunculopontinus and the substantia nigra in normal and decorticated rats.

The electrophysiological characteristics of neurons of the nucleus tegmenti pedunculopontinus (PPN), in particular of those projecting to the substantia nigra (SN), and the reciprocal influence between the PPN and SN were investigated in normal and decorticated rats. In intact animals 65 of the 363 PPN recorded neurons (17.9%) were activated antidromically by SN stimulation, 96 (26.3%) were inhibited after stimulation while 43 (11.8%) were activated. In decorticated rats excitatory responses were decreased (4.8%) while antidromic and inhibitory responses did not change substantially. Electrical stimulation of the PPN induced a brief short-latency excitation of SN neurons (26/77, 33.7%) which was not modified by removing the cortex bilaterally 7-10 days prior to the recording session. This excluded the possibility that corticofugal fibers could be involved in the excitatory responses evoked by PPN stimulation in SN neurons. The latency of the antidromic response evoked in PPN cells by SN stimulation ranged from 0.5 to 12.0 ms and the estimated conduction velocity of these PPN output neurons ranged from 1.1 to less than 0.5 m/s. The electrophysiological heterogeneity of PPN cells was supported also by the fact that two types of neurons, both projecting to the SN, could be distinguished on the basis of their spontaneous firing rate and impulse waveform. The first had a low spontaneous activity (0.5-8 spikes/s) with a triphasic impulse which lasted 3-4 ms. The second had a high firing rate (15-20 spikes/s) and its impulse was usually biphasic and not longer than 3 ms.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

A microiontophoretic study on the nature of the putative synaptic neurotransmitter involved in the pedunculopontine-substantia nigra pars compacta excitatory pathway of the rat.

The nature of the synaptic transmitter involved in the excitatory fibers linking the nucleus tegmenti pedunculopontinus (PPN) to the pars compacta of the substantia nigra (SNPC) was investigated using microiontophoretic techniques in rats anesthetized with ketamine. Among the SNPC cells activated orthodromically by PPN electrical stimulation, only a few cells were weakly excited by iontophoretically administered acetylcholine (Ach) while most were not affected. Conversely all cells were promptly and powerfully excited by short pulses of glutamate (GLU). The administration of the GLU antagonists glutamic acid diethyl ester (GDEE) and D-alpha-aminoadipic acid (DAA) reversibly and simultaneously suppressed both the PPN-evoked orthodromic response and the GLU-induced excitation of SNPC cells without affecting their response to iontophoretic Ach. GDEE was more effective than DAA in counteracting the synaptically evoked excitation. On the other hand, atropine, while antagonizing the Ach response in those cells which were cholinoceptive, did not affect either the PPN-evoked or the GLU-induced excitation. Hence, despite the presence of cholinergic cells in the PPN region, Ach does not appear to be involved in the excitatory PPN-SNPC pathway. The present findings suggest that the excitatory PPN fibers innervating the SNPC may utilize GLU or a closely related amino acid as a neurotransmitter.

2-Aminoadipic Acid↗
PubMed1982

Cholesterol homeotasis in rats fed a purified diet.

The rate of whole bodyb cholesterol synthesis was measured in male Sprague-Dawley rats fed either a standard chow, cereal-based diet or a semi-synthetic purified diet consisting of casein, sucrose and lard. The purified diet significantly decreased daily fecal excretion of neutral and acidic sterols, the specific acitvity of hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase, the bile acid pool size, and total daily cholesterol synthesis in the rat, while increasing plasma cholesterol concentrations and the total body content of cholesterol. The increased body content of cholesterol occurred primarily in muscle and connective tissue and not in the liver. The data demonstrate the importance of quantitating the net tissue accumulatin of cholesterol for accurate measurement of daily sterol synthesis in growing animals when sterol balance measurements are used. Tissue accumulation accounted for 7% of total daily cholesterol synthesis in rats fed the cereal diet, and 20% of daily synthesis in animals fed the purified diet.

Animals↗
PubMed1981

Thin-layer and gas--liquid chromatographic identification of neutral steroids in human and rat feces.

Natural steroids from rat and human feces were fractionated by sequential thin-layer chromatography (TLC) on Florisil, silica gel, and silver nitrate-impregnated silica gel and analyzed by gas--liquid chromatography (GLC). Cholesterol, coprostanol, and coprostanone accounted for more than 95% of the endogenous neutral steroid in human feces, the remainder being predominantly cholestanol. In addition, evidence was obtained for the presence in human feces of trace amounts of epicoprostanol and cholestanone. In rat feces, several cholesterol precursors that probably originated in the skin (and were ingested during fur=licking) were detected in relatively large amounts, accounting for as much as 27% of the total fecal neutral steroids, whereas these steroids were quantitatively trivial in human feces. As with cholesterol, the major dietary plant sterols (sitosterol, campesterol, and stigmasterol) were converted by intestinal bacteria to the corresponding coprostane and ketonic derivatives during intestinal transit in both human beings and rats. This combined use of TLC and GLC provided for the separation of steroids of endogenous and dietary origin that could not be resolved by either system alone. A majority of the fecal steroids could be tentatively identified by their chromatographic behavior in different TCL systems and on GLC, even when reference standards were unavailable.

Animals↗
PubMed1981

Origins of fecal neutral steroids in rats.

The origins of rat fecal neutral steroids were studied in male and female animals fed a sterol-free diet and maintained in an isotopic steady state. The specific activity of fecal cholesterol was found to be consistently lower than that of plasma cholesterol and of the fecal bile acids, indicating that a considerable portion of the fecal neutral steroids was derived from cholesterol not in equilibrium with the rapidly exchangeable pool of body cholesterol. This non-exchanging fraction of neutral steroids was larger in male than in female rats; it appeared to have at least two origins: skin surface lipids licked off fur, and sterols newly synthesized by the intestinal mucosa and secreted into the gut lumen. When the ingestion of skin sterols rich in cholesterol precursors was minimized, the proportion of the non-exchanging fraction of fecal neutral sterols fell somewhat, but the output of cholesterol precursors dropped markedly. This suggests that a significant portion of the non-exchanging fecal cholesterol fraction originated in the intestinal wall by secretion. It can be concluded that the fecal neutral steroids of rats originate primarily from three sources: 1) de novo cholesterol synthesis by the intestinal mucosa, 2) ingested dietary, skin, and fecal sterols, and 3) a rapidly exchangeable cholesterol pool excreted through bile, the intestinal wall, or both.

Animals↗