Biomedical subjects

A Berardi

Publications and source records attributed to A Berardi.

At least 19 recordsLinked to original sources

PubMed1996

Differential response to the cholinergic agonist arecoline among different cognitive modalities in Alzheimer's disease.

Nine patients with possible or probable dementia of the Alzheimer type were tested on nine cognitive tests prior to (two times) and during continuous intravenous administration of five different doses of the muscarinic cholinergic agonist arecoline (1, 4, 16, 28, and 40 mg/day). The present analysis examined whether improvement on cognitive testing for each patient during arecoline treatment was most likely to occur at the same dose for all tests or whether different test scores improved at different doses of arecoline. Results indicated there were significant differences among tests in the dose at which most patients showed improved cognitive performance. These differences may have therapeutic significance, as verbal ability tended to improve at low doses of arecoline, whereas attention and visuospatial ability tended to improve at higher doses of arecoline.

Aged↗

PubMed1996

Clinical pharmacokinetics of arecoline in subjects with Alzheimer's disease.

OBJECTIVE: To study the pharmacokinetics and pharmacodynamics of intravenously administered arecoline in subjects with Alzheimer's disease. METHODS: Plasma arecoline concentrations were measured during and after high-dose (i.e., 5 mg intravenously over 30 minutes) and up to 2 weeks of continuous multiple-dose steady-state intravenous infusions of arecoline in 15 subjects with mild to moderate Alzheimer's disease. During multiple-dose infusions, the dose of arecoline was escalated from 0.5 to 40 mg/day. Psychometric tests were administered at baseline and every other dose to determine an "optimal dose" for each subject. This dose then was administered for 1 week using a randomized, placebo-controlled, double blind, crossover design. Plasma drug concentrations were measured by GC-MS. RESULTS: The optimal dose of arecoline varied fourfold across subjects (4 mg/day, n = 6; 16 mg/day, n = 3) with mean plasma half-lives of 0.95 +/- 0.54 and 9.3 +/- 4.5 (SD) minutes. Clearance and volume of distribution were 13.6 +/- 5.8 L/min and 205 +/- 170 (SD) L, respectively. At the dose that optimized memory, the mean plasma level was 0.31 +/- 0.14 (SD) ng/ml, and it predicted the optimal dose in all subjects. CONCLUSIONS: Because optimal dose variation is due to differing plasma kinetics, the plasma arecoline level measured at a single infusion rate can be used to choose the optimal dose for memory enhancement in patients with Alzheimer's disease.

Aged↗

PubMed1995

Brain mechanisms in human classical conditioning: a PET blood flow study.

Five healthy male subjects participated in a classical conditioning experiment, and positron emission tomography (PET) was used to compare regional cerebral blood flow before and after conditioning. The subjects participated in three different experimental phases. In the first (habituation) phase they listened to 24 repetitions of a tone with random intervals. In the second (acquisition) phase, the tone was paired with a brief shock to the wrist. In the third (extinction) phase, the tone was presented alone again. 15OPET scans were taken during the habituation and extinction phases. Because the habituation and extinction phases were similar, any difference in blood flow to the tones presented during extinction probably reflected conditioning that occurred during the acquisition phase. Statistical parametric mapping (SPM) analysis of the PET data showed significantly increased activation in the right hemisphere in the orbito-frontal cortex, dorsolateral prefrontal cortex, inferior and superior frontal cortices, and inferior and middle temporal corticies. The only activated areas in the left hemisphere were area 19 and the superior frontal cortex. The results are interpreted as evidence for the involvement of cortical areas in human classical conditioning.

Acoustic Stimulation↗

PubMed1995

Pharmacokinetics of reboxetine in healthy volunteers. Single oral doses, linearity and plasma protein binding.

The pharmacokinetics of reboxetine, a new antidepressant agent, were found to be close to linear in a crossover study comparing administration of single 2, 3, 4, and 5 mg capsule doses in 15 healthy male volunteers, and in the same study the capsules were bioequivalent to the proposed therapeutic tablet formulation (4 mg). Kinetic analysis was based on HPLC assay of reboxetine in plasma and urine collected up to 72 h after each administration. Plasma levels indicated a rapid absorption (tmax approximately equal to 2 h) and an elimination half-life of about 13 h. Clearance and volume of distribution were modest (ratios to bioavailability: CL/F approximately equal to 29 mL min-1; Vz/F approximately equal to 32 L); urinary excretion was approximately 9% of dose, corresponding to a renal clearance of only 3 mL min-1 (a value consistent with the rate of glomerular filtration of unbound drug). In vitro, binding to plasma proteins, estimated from radioactivity levels following dialysis of 14C-labelled reboxetine, appeared to be dominated by alpha 1-acid glycoprotein without marked saturation up to plasma concentrations of over 500 ng mL-1 (2.8-3.1% unbound with human plasma from three additional volunteers; 1.8-2.0% for 2 gL-1 orosomucoid alpha 1-acid glycoprotein, and 46.4-47.4% for 40 g L-1 albumin), whilst the mean Cmax in the current study was much lower (164 ng mL-1 after a 5mg dose).

Adult↗

PubMed1995

Neuroendocrine responses to intravenous infusion of arecoline in patients with Alzheimer's disease.

We have reported that arecoline, a muscarinic receptor agonist replicably enhanced verbal memory in five of nine subjects with Alzheimer's disease (AD). To investigate the mechanism of cognitive improvement, circulating hormone measurements were made during high-dose acute and low-dose chronic intravenous (i.v.) arecoline administration to AD patients. Acute hormone responses were measured during, and for 6 h after, infusion of arecoline 5 mg i.v. over 30 min. Chronic responses were measured in cognitive responders during continuous i.v. infusion of arecoline escalating over 2 weeks (0.5-40 mg/day) and then during a 1 week infusion of the dose optimizing cognition (4-16 mg/day). Acute arecoline administered to 14 subjects produced unpleasant side-effects (e.g. nausea, vomiting), mean adrenocorticotrophic hormone (p = .0006), cortisol (p = .0001) and beta-endorphin (p = .0001) levels were elevated. During chronic arecoline treatment, no side-effects occurred and plasma cortisol, adrenocorticotrophic hormone and beta-endorphin levels were unchanged in nine subjects overall and in five cognitive responders. Thus, high-dose arecoline activates the hypothalamic-pituitary-adrenal (HPA) axis and may increase other anterior pituitary hormone levels, likely representing a 'stress response', but cognition-enhancing, low doses of arecoline do not produce a glucocorticoid response. Hence, arecoline-induced memory improvement is not due to the induction of 'stress' nor to the elevation of peripheral corticosteroid levels.

Adrenocorticotropic Hormone↗

PubMed1995

Treatment of Alzheimer disease by continuous intravenous infusion of physostigmine.

Physostigmine, a reversible and nonselective cholinesterase inhibitor, administered by steady-state, continuous intravenous infusion to carefully selected subjects with mild-moderate Alzheimer disease, produced significant but modest improvement in memory in five of nine subjects. Drug dosing was limited by the occurrence of adverse effects. Apparent tolerance to adverse effects was observed in two subjects when the dose of physostigmine was escalated slowly over at least 2 weeks. Steady-state cholinesterase inhibition by physostigmine appears to produce sustained cognitive improvement in some subjects with Alzheimer disease without substantially altering its therapeutic index.

Aged↗

PubMed1994

Anterior cruciate ligament mechanoreceptors. Histologic studies on lesions and reconstruction.

The fate of mechanoreceptors was studied in torn and reconstructed anterior cruciate ligaments in animals and in humans. In untreated anterior cruciate ligament lesions in humans, morphologically normal mechanoreceptors remained in the ligament for 3 months after the injury. After that time, their number gradually decreased. By the 9th postinjury month, only a few free nerve endings were present. Even free nerve endings were totally absent in the biopsy specimens from 1-year-old lesions. In experimental animals, anterior cruciate ligament reconstruction with autologous patellar tendon resulted in the presence of mechanoreceptors in the reconstructed anterior cruciate ligament. When an artificial ligament was used, no mechanoreceptors were found. Morphologically normal mechanoreceptors were present in 2 patients with a lax biologic anterior cruciate ligament reconstruction 9 and 10 years after the operation.

Animals↗

PubMed1993

Diagnosis of neurofibromatosis type 1 using RFLPs tightly linked to gene.

This study reports the results of a linkage analysis in nine families with members who had neurofibromatosis type 1 (NF1), using five restriction fragment length polymorphisms (RFLPs) tightly linked to the NF1 locus. The purpose of this analysis was to determine whether the at-risk individuals were carrying the NF1 allele and whether the nine families would be informative for prenatal testing. The families included 25 patients with NF1, 3 individuals at risk for NF1, and 11 unaffected subjects, with a total of 39 family members and 12 matings. In 6 matings two or more flanking probes were informative, in 3 matings only one probe was informative, and in the other 3 no probe was informative. DNA linkage analysis showed with more than 98% probability that the 3 at-risk individuals did not carry the NF1 mutation. No recombination events were observed. In 6 families it will be possible to do a DNA prenatal diagnosis if this type of test is requested. The NF1 gene has been identified and direct testing for the NF1 mutation is now possible. Linkage testing, however, will probably remain useful and complementary to direct analysis of the NF1 gene to reveal intragenic recombination events and for diagnosis in families in which the detection of mutation is difficult.

Adult↗

PubMed1993

Central nervous system imaging in reevaluation of patients with neurofibromatosis type 1.

We report the results of the reevaluation of 24 patients with neurofibromatosis type 1 (NF1) using central nervous system (CNS) imaging techniques. The first examination by computed tomography (CT) or magnetic resonance imaging (MRI) indicated the presence of optic glioma in three cases, "unidentified bright objects" (UBOs) in six, and a suspected right frontal tumor in one. In two patients optic glioma and UBOs were both present and in one of them a bulbar tumor was also suspected. Later imaging examinations revealed the appearance of optic glioma in three more cases and UBOs in nine. In two of these patients both optic glioma and UBOs were present. This study indicates that the likelihood of detecting imaging abnormalities in patients with NF1 increases when systematic follow-up is performed. Optic gliomas are characteristic of pediatric patients; they rarely give rise to clinical manifestations (1/6 cases) and in general progress very slowly. For these reasons, therapeutic strategy must be carefully considered and individually decided. UBOs are very frequent findings in pediatric patients with NF 1 and therefore they must be considered diagnostically relevant. They are not related to clinical manifestations and spontaneous regression has been observed. The nature of these imaging abnormalities is still unknown, but because they do not behave like tumors, useless and dangerous therapeutic procedures should not be employed.

Adolescent↗

PubMed1993

Relationship between café-au-lait spots as the only symptom and peripheral neurofibromatosis (NF1): a follow-up study.

We re-examined 21 children with the possible diagnosis of peripheral neurofibromatosis (NF1) based on the presence of café-au-lait (CAL) spots as the single clinical finding. We evaluated whether "typical" or "atypical" appearance of the spots was important for the final diagnosis and whether the co-existence of other non-specific signs (e.g. pectus excavatum) were of any significance for the final diagnosis. In 8/14 (57.1%) cases with "typical" CAL spots, the diagnosis of NF1 was finally established on the basis of other criteria. For the other 6 patients the diagnosis is not yet definitive but highly probable on the basis of the presence of macrocephaly, pectus excavatum and/or MRI findings. Only one patient among five with "atypical" CAL spots possibly has NF1.

Brain Neoplasms↗

PubMed1993

Memory improvement without toxicity during chronic, low dose intravenous arecoline in Alzheimer's disease.

Arecoline, a cholinergic agonist, administered at low doses by continuous intravenous infusion for up to 2 weeks, significantly and replicably improved memory in five of nine subjects with mild-moderate Alzheimer's disease. During dose finding, performance on a verbal memory task improved with an inverted U-shaped relation to dose. Six of nine subjects were classified as responders. During blinded, placebo-controlled, individualized optimal dosing for 5 days, verbal memory again improved in five of six responders but not in any non-responder. No adverse drug effects occurred. Arecoline, and possibly other cholinergic agonists, can safely improve memory in Alzheimer's disease at doses much lower than previously studied.

Aged↗

PubMed1992

Evaluation of four different methods for platelet freezing. In vitro and in vivo studies.

This report describes our experience with various techniques for the freezing of platelet-rich plasma, removed from the final product after leukapheresis procedures performed on 14 hematological patients. A total of 194 platelet units were frozen for subsequent autologous transfusion, by the following four methods: (1) 6% dimethyl sulfoxide (DMSO); (2) a combination of 5% DMSO/6% hydroxyethyl starch; (3) 3% glycerol; (4) 5% glycerol/4% glucose. Each technique was evaluated by measuring the percentage of platelet recovery, malondialdehyde (MDA) production, and lactate dehydrogenase release. To investigate the safety and therapeutic effectiveness of the previously frozen platelets, in vivo comparison of four platelet freezing methods was made in 8 thrombocytopenic patients, using corrected platelet increment (CCI), determined at 24 h. Our in vitro results indicate that the cryopreservation with 6% DMSO, without controlled cooling rate, provides significantly (p less than 0.05) greater platelet recovery (75%) as compared to other systems. The decrease of MDA production and the increase in plasma lactate measured after the thawing process was less in the DMSO-frozen units than in the other platelet units. When platelets, cryopreserved by this method, were subsequently transfused into patients, a significantly better CCI (greater than 5,000/microliters) was obtained. In our series, 6 patients were entirely supported with frozen autologous platelets. It appears from this study that a better understanding of the physical and biochemical events occurring during the freezing process will improve platelet cryopreservation, allowing a more systematic use of frozen platelets in the support of thrombocytopenic patients.

Adolescent↗

PubMed1991

Effects of acute infusion of the muscarinic cholinergic agonist arecoline on verbal memory and visuo-spatial function in dementia of the Alzheimer type.

1. Treatment of patients with dementia of the Alzheimer type (DAT) with arecoline, a muscarinic cholinergic receptor agonist, reportedly improves performance on a picture recognition memory task, but not on other memory measures. To examine further possible performance improvements following arecoline treatment, patients with DAT were treated with a 30 min intravenous infusion of arecoline (5 mg). 2. Psychometric testing was done at five time points (two before and three following the infusion). Patients were tested on a memory task (Buschke selective reminding) and a test of visuo-spatial performance (figure copying). 3. No net change from baseline was seen in mean scores following arecoline infusion. However, the changes in performance on the two tasks were correlated (p less than 0.02) over subjects at 10 min but not at 1.5 or 5.5 hr following the infusion. 4. This result suggests that although individual patients vary in their response to a given dose of arecoline, their responses are consistent across types of tasks. Thus the lack of a mean drug effect may be due to individual differences in response rather than to a lack of response.

Aged↗

PubMed1991

Density gradient separation of hematopoietic stem cells in autologous bone marrow transplantation.

Recently, the principles of density gradient cell separation have been transferred to the marrow fractionation, and the Ficoll technique by using a COBE 2991 blood cell processor has been developed and widely employed as well. This method is particularly useful in view of a chemical antineoplastic purging intended for autologous marrow transplantation. Forty marrows, which derived from patients suffering with leukemia and lymphoma, were fractionated with Ficoll on a COBE machine and in vitro purged with Mafosfamide at a dose of 50 micrograms/ml/1 x 10e7 MN cells. The density gradient separation enables to reduce the initial volume to 10%, the contaminating RBC to less than 1%, the total nucleated cells to 25% (greater than 80% of MNC) sparing about 80% of the CFU-GM. After purging, the surviving hemopoietic progenitor cells were 2.5%. The clinical effects of the fractionated purged cells were studied in 11 autotransplanted patients and compared with 14 transplants performed with untreated buffy-coat marrow derived cells. Ficoll cells produced less adverse effects at the time of reinfusion, while, as expected, the time of hematopoietic recovery was delayed in these patients (mafosfamide treated cells). These results confirm the usefulness of the gradient density cell separation to reduce the side effects of the DMSO and to make reliable the Mafosfamide purging manoeuvre, preventing the interference of contaminating RBC aldehyde dehydrogenase.

Bone Marrow Transplantation↗

PubMed1991

Effects of long-term continuous infusion of the muscarinic cholinergic agonist arecoline on verbal memory in dementia of the Alzheimer type.

Alzheimer's disease (AD) is accompanied by depletion of cholinergic markers in the central nervous system. In an attempt to improve cognitive function in AD, arecoline (a muscarinic cholinergic receptor agonist) was given to patients with probable or possible AD in a two-phase design, and verbal memory function was examined. First, escalating doses of arecoline, range .5-40 mg/day, were administered by continuous intravenous infusion over a 2-week period. Based on neuropsychological test performance, an optimal dose of arecoline was identified, and this dose then was infused continuously for 5 days in a double-blind, placebo-controlled, counter-balanced trial. Long-term recall on a selective reminding task was significantly improved (from 11.8 to 20.1 words, p less than .05) during dose finding by arecoline at 4 mg/day. Two of eight patients were nonresponders; that is, they showed no improvement at any dose during the dose-finding study. Responders demonstrated significant improvement on total recall (p less than .05) during the double-blind study. These results indicate that some patients demonstrate reliable improvements of verbal memory during arecoline treatment.

Aged↗

PubMed1988

Concomitant purification of prostatic carcinoma tumor markers from human seminal fluid under nondenaturing conditions.

We report a protocol for concomitant purification to homogeneity of both prostatic acid phosphatase [orthophosphoric-monoester phosphohydrolase (acid optimum), EC 3.1.3.2] and prostate-specific antigen, from human seminal fluid. The method requires only two chromatographic steps: passage through an Affigel-Blue column and gel filtration HPLC. This is a fast, efficient procedure for purification of these two important tumor markers, which are specific for prostatic cancer.

Acid Phosphatase↗

PubMed1988

Seven-day storage of single donor platelets in polyolefin bags: clinical, biochemical, morphological and microbiological evaluation.

We compared the in vitro and in vivo function of fresh and stored platelet concentrates (PCs) collected by an automated continuous-flow blood cell separator (CS 3000 Fenwal) in a closed-system apheresis kit in order to evaluate the possibility of extending the storage time to seven days with the polyolefin container (PL-732). The initial 220 ml platelet volume (5.14 +/- 1.23 x 10(11) was divided into two parts. Half was transfused and the other half was stored for 7 days. All cultured units were negative for bacterial contamination. Mean counts for fresh and stored platelets were respectively 2.34 +/- 0.59 and 2.17 +/- 0.50 X 10(11)/100 ml of PCs (mean recovery 88.7 +/- 11.9%). The pO2 levels were maintained during storage (179.9 +/- 30.5 mmHg) but pCO2, pH, LDH, osmolality, glucose consumption, bicarbonates, ATP, and osmotic stress values changed significantly after 7 days storage. From a clinical point of view, in 14 patients receiving a total of 38 PC transfusions no statistically significant change in corrected post-transfusional levels was observed between fresh and stored PC. Biochemical and morphological data and clinical results suggest that PCs collected with CS-3000 blood cell separator in a closed system and stored for 7 days in polyolefin bags (PL-732) can be satisfactorily employed in clinical practice.

Blood Platelets↗

PubMed1988

Enrichment of marrow hemopoietic progenitor cells using a blood cell processor.

A total of 93 bone marrows (BM) from normal donors and patients were processed using the IBM-COBE 2991 blood cell washer to produce a concentrated buffy coat (BC) for either bone marrow transplantation (BMT) or cryopreservation for subsequent autologous BMT. The reduction in volume was 73.3 +/- 8.5% and nucleated blood cells (NBC) recovery was 87.1 +/- 9.1% of original marrow. Red blood cell (RBC) and platelet (PLT) contamination was reduced 64.5 +/- 10.9% and 41.2 +/- 24.1%, respectively. Clonogenic activity indicated that the NBC fraction was highly enriched in hematopoietic progenitor cells (greater than 100%) as assessed in vitro (CFU-GM). Results were not affected by diagnosis, initial marrow volume or cell count of the BM suspension. We conclude that this is a simple and reproducible method using blood bank, facilities and permits BC preparation from BM without significant loss of hematopoietic progenitor cells.

Bone Marrow Cells↗