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Biomedical subjects

M Franceschi

Publications and source records attributed to M Franceschi.

At least 109 records · Page 6Linked to original sources

Metabolism of 99mTc-L,L-ethyl cysteinate dimer in healthy volunteers.

99mTc-L,L-Ethyl cysteinate dimer (ECD) is a brain-perfusion imaging agent, which exhibits selective retention in brain and rapid renal excretion. The pharmacokinetics and metabolism of ECD were studied in vivo in healthy humans and its metabolism in vitro was evaluated in tissue from human brain. In vitro studies showed 99mTc-L,L-ECD to be metabolized to a polar 99mTc-complex. It has been shown previously that most of the activity of 99mTc retained in the brain of the monkey in vivo is in the form of a polar 99mTc complex (Walovitch, Hill, Garrity, Cheesman, Burgess, O'Leary, Watson, Ganey, Morgan and Williams, 1989). Whole body images of the distribution of 99mTc-L,L-ECD (10 mCi i.v.) in four adult males showed good uptake in brain, with slow elimination (6.8 +/- 0.3% injected dose [mean +/- SE] at 5 min), with less than 25% decrease in activity during 4 hr of imaging. Background areas in the head and lungs washed out rapidly, providing ideal imaging conditions. Elimination of 99mTc from venous blood was biphasic, with a plateau of activity between 2-15 min (7-8% injected dose) before a terminal phase, with a t1/2 of a few hours. Organic extraction of whole venous blood showed greater than 50% of the 99mTc-L,L-ECD to be in the form of polar metabolite(s) at 5 min. They were identified in the urine as the 99mTc ethylenediylbis-L-cysteine, monoethyl ester complex (ECM) and the 99mTc-ethylenediylbis-L-cysteine complex (EC). These metabolites were excreted rapidly (75% injected dose in urine within 6 hr). The results of this study support the hypothesis that the selective retention in brain, rapid blood elimination and renal excretion of 99mTc-L,L-ECD is due to its metabolic transformation to polar end products.

Adult↗

ACTH and cortisol secretion in patients with Alzheimer's disease.

The "glucocorticoid cascade hypothesis" for pathological ageing of the brain is supported by strong experimental data, but the clinical correlates are far less clear. The basal ACTH and cortisol secretion have been studied before and after the dexamethasone suppression test in patients in the early stages of clinically probable Alzheimer's disease and in controls, and the results were all normal. These findings do not support the hypothesis that the pathological brain ageing of Alzheimer's type is caused by hyperactivity of the pituitary-adrenal axis.

Adrenocorticotropic Hormone↗

Sleep-related growth hormone secretion in human obesity: effect of dietary treatment.

Eight obese patients (4 male, 4 female; mean age = 35.9 years) before [mean body mass index (BMI) = 37.1] and after (mean BMI = 31.4) weight loss by means of a mixed hypocaloric diet were compared with 8 lean subjects (4 male, 4 female; mean age = 37.1 years, mean BMI = 22.3) in a study of their nocturnal sleep patterns and sleep-related growth hormone (GH) secretions. Although no sleep disorders (in particular, sleep apnea and hypersomnia) were observed, GH secretion was markedly altered in obese patients that showed no sleep-related GH peaks. After weight loss, the sleep architecture in obese subjects was unchanged. On the contrary, GH peak appeared to be only partially restored and delayed until after stage III-IV of non-REM sleep. Our study on obese subjects suggests that the altered nocturnal GH secretion, probably related to a hypothalamic dysfunction, may be the result of the obesity per se.

Adult↗

[The behavior of the arterial pressure at rest and under exertion in normotensive and hypertensive subjects exposed to acute hypoxia at a median altitude].

In order to evaluate blood pressure changes at rest and during effort in response to moderate altitude acute hypoxia, we performed noninvasive blood pressure monitoring and maximal bicycle stress testing in 10 normotensive and 13 untreated mild hypertensive subjects at sea-level and in a mountain resort (m. 2572). Blood pressure was measured every 10 minutes by the Spacelabs 5200 pressurometer and bicycle stress test was performed at initial workload of 50 watts and steps of 50 watts every 3 minutes until exhaustion. Mean systolic blood pressure resulted unchanged in the normotensive subjects (120.8 +/- 10.6 vs 121.5 +/- 6.9 NS) while in the hypertensive ones it increased slightly at 2572 m. (131.0 +/- 12.3 vs 137.0 +/- 13.1 NS). Mean diastolic blood pressure did not increase significantly at 2572 m in either group (respectively from 74.5 +/- 90 to 80.1 +/- 7.9 NS and from 88.3 +/- 10.2 to 94.7 +/- 10.7 NS) even if blood pressure increase was relevant in some hypertensive subjects. During the monitoring, heart rate increased at 2752 m in both groups, even if this difference was significant in the hypertensive group only (respectively 82.8 +/- 11.8 vs 94.3 +/- 13.2 in normotensive subjects-NS-and 88.0 +/- 6.3 vs 104.0 +/- 7.8 in hypertensive subjects-p less than 0.001). During the ergometric test submaximal systolic blood pressure (100 and 150 watts) increased slightly in both groups, but this difference was significant in hypertensive subjects at a workload of 150 watts only (208.3 +/- 18.2 vs 219.3 +/- 19.2 p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Tumor marker determinations.

A combination of 2 or 3 tumor markers was determined in the serum of 478 patients with malignant tumors. In 195 out of 213 patients with differentiated thyroid cancer and without relapse or metastases, the Tg concentration has undetectable. In 9 patients with nonfunctioning thyroid metastases the Tg level was correlated with the progress of the disease or the success of the treatment. In 114 patients with gastrointestinal cancer CA 19-9, TPA and IAP were measured simultaneously. The highest discrepancies between patients with relapse or metastases (increased values in 1/2 of patients) and patients without relapse or metastases (increased values in 1/4 of patients) were given by CA 19-9. In the serum of 90 patients with breast cancer increased CA 15-3 values were found in 2/3 of patients with relapse or metastases and in 1/4 of patients without signs of tumor. A combination of universal tumor markers TPA and IAP had no value in monitoring 26 patients with melanoma.

Biomarkers, Tumor↗

Effect of L-alpha-glyceryl-phosphorylcholine on amnesia caused by scopolamine.

The present study was carried out to test the effects of L-alpha-glycerylphosphorylcholine (L-alpha-GFC) on memory impairment induced by scopolamine in man. Thirty-two healthy young volunteers were randomly allocated to four different groups. They were given a ten day pretreatment with either L-alpha-GFC or placebo, p.o., and on the eleventh day either scopolamine or placebo, i.m. Before and 0.5, 1, 2, 3, and 6 h after injection the subjects were given attention and mnemonic tests. The findings of this study indicate that the drug is able to antagonize impairment of attention and memory induced by scopolamine.

Adult↗

Prevalence of dementia in adult patients with trisomy 21.

Neuropathological lesions characteristic of Alzheimer's disease (AD) are found in all the brains of patients with trisomy 21 who die after age 40 years. However, clinical signs of AD are much less frequent in these patients. Previous studies indicate prevalence figures ranging from 15% to 51% of adult patients. We report here on the prevalence rate of dementia in a population of adult patients with trisomy 21 with mild retardation living at home. For all these patients accurate and reliable anamnestic data could be obtained from parents and caregivers. All underwent neurological examination, cognitive testing, and, if necessary, further bioimaging and neurophysiological studies. Dementia was diagnosed according to clinical NINCDS/ADRDA criteria slightly modified. Dementia was found in 9 of 50 (18%) patients age 20-52 years, but its prevalence increased from 0 in the age group 20-29, to 33% in the age group 30-39, and to 55% in the age group 40-52. All the demented patients had signs of brain atrophy on CT scans and slow EEGs. Dementia is an important problem for patients with trisomy 21 older than age 30 years.

Adult↗

Cardiac autonomic dysfunction during sleep in some neurological diseases.

The most widely used tests for the investigation of the autonomic nervous system (ANS) functioning measure the heart rate (HR) variations during wakefulness. Most tests have some limitations: they require patient collaboration and can be modified by his or her emotional status. We studied HR variability in relation to body movements during sleep in some neurological diseases. Our method seems to be better than the traditional tests in detecting early cardiac ANS damage, especially when the patient is non-co-operative for ANS evaluation during wakefulness after various stimuli.

Adult↗

Myocardial clearance of Tc-99m hexakis-2-methoxy-2-methylpropyl isonitrile (MIBI) in patients with coronary artery disease.

Myocardial clearance of the new cationic, lypophilic myocardial perfusion agent, Tc-99m-hexakis-2-methoxy-2-methylpropyl isonitrile (MIBI) was studied in nine patients with coronary artery disease. Regional time-activity curves were determined from serial postexercise myocardial SPECT images after a single dose of Tc-99m MIBI. There were significant differences between the clearance rates from normal and ischemic myocardium. Tc-99m MIBI washout from normal myocardium was 27 +/- 8% by 6 hours after injection. Clearance from mild myocardial defects (initial activity greater than 60% of the activity in normal myocardium) was 16% by 6 hours in six patients. No washout was detected by 6 hours in the three patients with severe myocardial defects. The ratio between the activity in ischemic and normal myocardium increased from 0.70 +/- 0.08 to 0.80 +/- 0.13 and 0.84 +/- 0.13 at 4 and 6 hours after injection in the patients with mild defects. In the patients with large defects, the ratio increased from 0.42 +/- 0.09 to 0.54 +/- 0.07 at 6 hours. It is concluded that, while redistribution is substantially slower than with Tl-201, image interpretation and data evaluation should be approached cautiously when imaging is delayed 4 hours or more after injection of Tc-99m MIBI. Quantitative techniques aimed at evaluating the extent and intensity of myocardial ischemia will be particularly affected.

Aged↗

Surname versus gene structure of a small isolate.

A hierarchical partition of the Wright coefficient of inbreeding (F) is shown for an isolated population (about 2000 inhabitants) from a mountainous region of Tuscany (Italy) with regard to both surnames and genes. At total population level surname variation proves substantially consistent with the observed genetic differentiation of the isolate. Analysis of parental isonymy reveals that the population is structured in subunits and it is concluded that the unit population of the region may be very small, practically coinciding with the village (less than 500 inhabitants). The agreement of 'demographic' and genetic structures is less satisfactory at this level, partly because of subsample size, but we conclude that analysis of surnames may give at least a rough idea of the genetic structure of the population.

Consanguinity↗

Clinical and epidemiological aspects of Alzheimer's disease with presenile onset: a case control study.

Little is known regarding the pathogenetic factors for Alzheimer's disease (AD). We studied 63 AD patients in order to evaluate if there were clinical subtypes of AD and whether prior illnesses and life-styles were involved in the development of the disease. In our patients selected for onset of symptoms before age 65 we did not find any significant clinical heterogeneity. Furthermore, we found no data in the medical history that are predictive for the development of presenile AD but observed a significantly increased frequency of dementia in the families of AD patients in comparison to controls.

Age Factors↗

Cortical pathophysiology and clinical neurologic abnormalities in acute cerebral ischemia. A serial study with single photon emission computed tomography.

We studied brain cortical radioactive tracer activity in a consecutive series of nine patients with acute hemispheric ischemic stroke at their first cerebral ischemic stroke at their first cerebral ischemic episode. Results from N,N,N'-trimethyl-N'- (2-hydroxy-3-methyl-5-[123-I]-iodobenzyl)-1,3 propanediamine-2HCl (four patients) and technetium Tc 99m hexamethylpropyleneamine oxime (five patients) single photon emission computed tomographic studies were compared with x-ray computed tomography (CT) and clinical findings within the first 48 hours, on day 10, and on day 30 after the clinical ictus. Cortical hypoactivity agreeing with the clinical findings was found on all initial scans but not in the follow-up studies. Cortical activity on the affected side in patients with stroke was significantly lower when compared with cortical activity in sex- and age-matched controls (n = 21). Computed tomography (with contrast) was less sensitive in detecting the ischemic lesions. These studies demonstrate that in the acute phase of stroke there is a single photon emission computed tomographic cortical disturbance that agrees with clinical findings, even when computed tomography scan infarction is limited to subcortical structures.

Adult↗

Effects of flunitrazepam on cognitive functions.

The effects of various oral doses (1, 2, 4 mg) of flunitrazepam on vigilance, attention, immediate memory, short-term memory, learning, non-consolidated and consolidated long-term memory were determined. Twelve healthy young male volunteers were given placebo or flunitrazepam in a double-blind, random latin-square sequence, crossing over every 2 weeks. Volunteers completed a battery of tests at night, 3.5 h after drug administration, and in the morning, 10 h after drug administration. Flunitrazepam 1 mg did not significantly impair any of the functions tested at night, while 4 mg impaired vigilance, attention, immediate memory, short-term verbal memory and learning. The impairments of immediate and short-term memory seem to be related and proportional to reductions in vigilance and attention. Doses of 2 mg and 4 mg impaired the speed of learning but did not decrease the amount of material learned. Flunitrazepam caused dose-related impairment of long-term memory, both consolidated and not. This reduction of long-term memory does not seem to be related to the impairments of vigilance, attention or learning. The lowest dose did not modify vigilance and learning in any subject, improved attention in half of the subjects but reduced long-term memory in a similar number of subjects. Therefore, our results indicate selective impairment of long-term memory. Since there were no differences between the effects on consolidated and non-consolidated memory, the amnesic effect of flunitrazepam seems to be due to a decrease in the storage of memory traces. There were no clear generalized residual effects in the morning after administration.

Adult↗

Neuron-binding antibodies in Alzheimer's disease and Down's syndrome.

We used an indirect immunoperoxidase technique (Avidin-Biotin system) to study the sera of patients with "clinically probable" Alzheimer's disease (AD) and with Down's Syndrome (DS), compared with age-matched controls. Diluted sera were incubated with paraffin sections of hippocampus, frontal, temporal, and parieto-occipital lobes from normal human brains. Biotinylated anti-human goat gamma-globulins were used as secondary antisera. A significantly greater percentage of neurons were immunostained in all the brain regions (frontal, temporal, and parieto-occipital lobes and hippocampus) incubated with sera of AD patients than with sera of DS patients or of controls. This indicates that AD patients have an excess of circulating neuron-binding antibodies (NBAs), mainly reacting with cytoplasmic structures. NBAs could be either the cause or the result of the cerebral lesion found in AD. This study is not able to answer this question, but some previous data from our own and other laboratories suggest that NBAs have a role in the pathogenesis of AD lesions. Since we found no increase of NBAs in DS patients, the brain lesions in DS appear to have a different pathogenesis.

Aged↗

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History, Modern 1601-↗

Nonrefractory temporal lobe epilepsy: 1.5-T MR imaging.

Thirty-one patients with temporal lobe epilepsy (TLE) of mild to moderate severity, well controlled by pharmacotherapy (nonrefractory TLE), and with negative findings at computed tomography, were studied with magnetic resonance (MR) imaging at 1.5 T. Examination disclosed significant findings in 16 patients: mesial temporal abnormalities (n = 9), basitemporal abnormalities (n = 2), and alterations in frontoparietal white matter (n = 5). Coronal views and sequences with a 120-msec echo time (TE) depicted lesions in 16 patients; axial views depicted lesions in only nine of 16 patients; sequences with a 35-msec TE depicted lesions in only ten. These results underline the importance of screening with MR imaging in nonrefractory TLE patients and suggest that the MR imaging sequence of choice is a thin-section, coronal, T2-weighted sequence.

Adolescent↗

Tuberoinfundibular dopaminergic function in Parkinson's disease.

A deficit of nigrostriatal, mesocortical and mesolimbic dopamine systems in Parkinson's disease is well known. We know less about the involvement of tuberoinfundibular dopamine (TID) systems. In untreated (naive or wash-out) men with Parkinson's disease, we studied TID function through basal and stimulated plasma levels of growth hormone, prolactin and thyrotropin. Only minor abnormalities in prolactin responses to thyrotropin-releasing hormone were found, probably reflecting denervation hypersensitivity. TID function is preserved in men with Parkinson's disease.

Aged↗