Diagnostic, therapeutic, ethic and legal issues in caring for dementia: the viewpoint of medical representative in Modena (Italy).
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Biomedical subjects
Publications and source records attributed to M Pinelli.
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This study was performed to evaluate the relation between a stable personality trait, a mood state and immune response to an examination stress. A self-reported measure of emotional stability (BFQ-ES scale) was obtained in a sample (n = 39) randomly selected from 277 cadets; this personality trait was also investigated by completing a neuroticism scale (Eysenck personality inventory) and a trait-anxiety scale (STAI). Natural killer (NK) cell activity was measured at baseline, long before the examination time and the examination day. The state-anxiety scale evaluated the response to the stressful stimulus. Taking subjects all together, the academic task did not result in significant modification over baseline in NK cell activity. Subjects were then divided into three groups based on emotional stability and state-anxiety scores: high emotional stability/low anxiety, medium, and low emotional stability/high anxiety. Examination stress induced significant increases in NK cell activity in the high emotional stability/low anxiety group, no effect in the medium group, and significant decreases in the low emotional stability/high anxiety group. The repeated-measure ANOVA revealed a significant interaction of group x period (baseline vs. examination) for both lytic units and percent cytolysis. The results did not change after introducing coffee and smoking habits as covariates. Our findings suggest that the state-anxiety acts in concert with a stable personality trait to modulate NK response in healthy subjects exposed to a psychological naturalistic stress. The relation between anxiety and poor immune control has been already described, whereas the ability of emotional stability to associate with an immunoenhancement has not yet reported. The peculiarity of our population, a very homogeneous and healthy group for life style and habits, can have highlighted the role of emotional stability, and may account for the difference with other studies.
We have used a great toe mini wrap-around flap for reconstruction of the thumb at, or distal to, the interphalangeal joint. Our series included 12 patients with traumatic amputations. A flap including the entire nail and most of the distal phalanx of the great toe was used. Eleven of the grafts survived. Sensibility was good with an average of 10 mm static two-point discrimination (range, 5-15) and there were no complaints of cold intolerance. All patients were pleased with the appearance of the thumb and there was no significant morbidity at the great toe donor site. The great toe mini wrap-around flap is an excellent reconstruction technique for selected patients with distal thumb amputations.
The consistency of measures from informants' report and from objective testing, both incorporated into the CAMDEX interview, was tested for elderly persons with mild dementia (n = 46), with moderate dementia (n = 41), and without cognitive impairment (controls, n = 56). Informants' reports permitted grading severity of dementia and provided measures of memory and mental functioning in everyday activities highly related to indices derived from objective testing.
Searches for MHC-encoded disease susceptibility genes have led to considerable knowledge of the content of the class I region. In an effort to further understand the nature of the five 6.7 family members previously mapped to this region of the genome, we have further analyzed the cross-reactive members of the family and have observed additional genomic instability within the HLA-A subregion. Such genomic variation may underscore the slower evolutionary rates of the HLA-A allelic family and the extended linkage disequilibrium of markers distal to this locus. Moreover, one of the largest genes associated with a member of the 6.7 family, the 3.8-1 gene found proximal to HLA-B, was found to demonstrate limited, composite similarity to RAG2 and complement C4a gene sequences. A pancreas-specific transcript embedded in a 6.7 cross-reactive fragment was found distal to HLA-H and suggests that the fragments have remained linked to transcriptionally active chromatin comprised of both a major class I gene and a second novel coding sequence since the time of their dispersal. The absence of a 6.7 fragment in the HLA-B subregions of higher nonhuman primates lends credence to the possibility that the great apes have suffered a recent deletion event within this region following the emergence of Homo sapiens.
We have cloned and sequenced a genomic region centromeric of the HLA-B locus from different MHC ancestral haplotypes. These haplotypes are associated with several diseases. The sequences were analyzed for coding potential and their relevance to disease associations were assessed with respect to the level of polymorphism. Analysis of sequences located approximately 25kb centromeric of HLA-B reveals the existence of fibroblast growth factor receptor related sequences. These sequences designated PERB1 (FGFR6) reveal 80% homology, at both nucleic acid and amino acid level, to the immunoglobulin domain 1 (Ig-1) of the human fibroblast growth factor receptor 3 (FGFR3) gene. Amino acid comparison of the Ig-1 domain of PERB1 to those of other FGFR molecules indicates that PERB1 is more closely related to FGFR3 and FGFR5 than to FGFR1, FGFR2 or FGFR4. Genomic sequence analysis, however, reveals no consensus splice sites and indicates the existence of inframe premature stop codons in the putative coding sequences. The results suggest that these sequences may represent FGFR gene fragments existing within the central MHC. Sequence analysis of the Mhc in 6 chimpanzee and one orangutan indicates that the existence of PERB1 predates the speciation of the three species. The fact that the MHC contains a mixture of functional and nonfunctional (pseudo) genes suggests that a functional copy of PERB1 (FGFR6) may exist within or in close proximity to the MHC.
The MHC contains clusters of polymorphic duplicated genes and gene sequences. It has been thought that these duplicated genes and sequences have arisen from single gene duplications. We compared the cloned region between TNF and HLA-B with the region in close proximity to HLA-A using sequence analysis and DNA hybridization. The results indicate that several sequences existing in the region centromeric of HLA-B are also present in close proximity to HLA-A. These include sequences belonging to the P5, BAT1, and PERB11 gene families as well as HLA class I gene sequences. Interestingly, when the two regions of approximately 200 kilobases are compared, the replicated sequences are organized similarly but in an inverted fashion suggesting the existence of an historical inverted en bloc duplication. Thus, we propose that the origin of these MHC gene clusters involves several mechanisms. In addition to single gene replication, a long-range duplication of a genomic block must have occurred. It is possible that a block at the telomeric end of the MHC represents a basic functional genomic unit conserved and duplicated en bloc.
Tourniquet paralysis is a serious complication after surgery. The authors report 15 cases recorded in their institution from 1972 to 1992. Seven were a consequence of routine operations on the upper limb and 8 were after microsurgical procedures. In the first group, the incidence of tourniquet paralysis was 1 in 7000 and this does not differ from published reports. In the second group, the incidence of complications is higher: 1 in 4300 cases. In all 15 cases the Tinel sign was absent. Great care was taken to distinguish all the painful conditions which ranged from simple hyperalgesia to allodynia and causalgia. The distressing aspect of tourniquet paralysis is that all the main nerves of the upper limb (median, radial and ulnar), distally to the elbow, are usually affected by the paralysis. In the two groups, the three nerves were affected in 13 cases and the ulnar nerve was partially spared in 3 cases. In both groups the radial nerve was more severely affected. It took an average of 105 days for complete recovery for the first group (range, 30-210 days) and 115 days for the second group (range, 20-180 days). Only in 1 patient in the first group was functional recovery incomplete. According to the authors' experience, general safety factors should be considered before using tourniquet. The tourniquet should be prohibited in patients with congenital susceptibility to nerve compression and should be used with caution in cases of underlying coagulation disorders and neuropathies, in tiny cachetic patients and in patients with systemic lupus erythematosus. In microvascular procedures its use should be limited to the first phase of replantation.
The purpose of developing the experimental model described in this study was to verify the hypothesis that free radicals are formed during ischemia-reperfusion of skeletal muscle. Spin trapping technique, along with electron spin resonance spectroscopy (ESR), directly indicates the presence of reactive radicals, which are widely considered to be important in tissue injury. The experimental model was a rat pedicled rectus femoris muscle flap. The femoral artery and vein were cannulated to inject the "spin trap" and collect the effluent flow. The spin trap agent was phenyl-t-butyl nitrone (PBN) and Hank's balanced salt solution. Three injections and collections were made: a) before ischemia; b) after ischemia of 15, 30, 60, 120, and 180 minutes, but before blood flow had been restored; and c) after blood flow had been restored. No ESR signal was detected either before the ischemic period or after only 15 minutes of ischemia. PBN radical adducts were detected after 30, 60, 120, and 180 minutes of ischemia. A similar signal was detected when PBN was injected during reperfusion 10 minutes after the ischemic periods. The study demonstrated the presence of free radicals in an in vivo intact skeletal muscle ischemia-reperfusion model.
We have used the novel strategy of overlapping yeast artificial chromosome (YAC) clones to localize a series of new transcripts within a 170 kb region of the human major histocompatibility complex (MHC), containing genes likely to be of importance for disease susceptibility. Using cloned genomic probes we have further localized these transcripts to a region 15 kilobases (kb) centromeric of HLA-B. In the liver there are at least four transcripts ranging in size between 7.5 kb and 3.4 kb, while in the lung two transcripts of 5.8 kb and 4.2 kb are detected. The possible implications of these transcripts for autoimmune disease are discussed, given that they are located in a region previously shown to be of importance for susceptibility to insulin-dependent diabetes mellitus and myasthenia gravis. Furthermore, we conclude that YACs as large as 360 kb are able to be used as probes to identify new transcripts and that the MHC region between HLA-B and BAT1 is the site of a large multiply spliced gene, provisionally designated PERB6.
OBJECTIVE: To compare pregnancy outcome following first-trimester fluoxetine (Prozac) exposure with pregnancy outcome in two matched control groups. Fluoxetine is a new antidepressant used by many young women. Currently, no published data exist on its safety in pregnancy. DESIGN: We prospectively collected and followed up 128 pregnant women exposed to a mean daily dose of 25.8 mg (+/- 13 mg) of fluoxetine during the first trimester and compared pregnancy outcome with two matched groups of women exposed during the first trimester of pregnancy to either nonteratogens or tricyclic antidepressants. RESULTS: Rates of major malformations were comparable within the three groups and did not exceed those expected in the general population. Women treated with fluoxetine had a tendency for increased risk for miscarriage when compared with women exposed to nonteratogens (relative risk, 1.9; 95% confidence interval, 0.92 to 3.92). The rate of miscarriages in the fluoxetine group was comparable with the tricyclic group (13.5% and 12.2% vs 6.8% in the nonteratogens). CONCLUSIONS: Our study suggests that the use of fluoxetine during embryogenesis is not associated with an increased risk of major malformations. Women exposed to both fluoxetine and tricyclic antidepressants tended to report higher rates of miscarriage; further studies will be needed to confirm this observation and to separate the effects of the psychiatric condition from the associated drugs. Long-term studies will be warranted to rule out potential developmental teratology of fluoxetine, which affects a central nervous system neurotransmitter.
The MHC is a region of some 4 megabases that has been studied intensively owing to the large number of diseases that are associated with susceptibility genes within this region of the genome. The total number of genes located within the MHC is now approximately 100, but more can be predicted. Recently identified genes within the MHC include PERB6, a large gene producing multiple transcripts located between HLA-B and TNF, and PERB1, a member of the protein tyrosine kinase-gene family. PERB6 was identified by YAC probing of tissue blots, while PERB1 was identified by genomic sequencing.
Two hallmarks of the MHC are the high degree of polymorphism apparent at multiple loci and "linkage disequilibrium." The data presented here suggest that a consequence of selection at a particular locus may be the inhibition of recombination through the accumulation of DNA sequence polymorphisms. Equivalent 6.4 kb regions from a locus, CL1, located approximately 25-30 kb centromeric of HLA-B, were sequenced for three ancestral haplotypes: A1,B8,DR3; A30,B18,DR3; and A1,B57,DR7. Comparison of the sequences indicated that the level of DNA sequence polymorphism was high when compared with the TNF region; approximately 80 single nucleotide differences were found when comparing any two sequences. In addition, multiple deletions/insertions were present. We believe that the degree of polymorphism within the CL interval may be adequate to at least partially inhibit recombination between the haplotypes studied.
Fetal exposure to nonsteroidal inflammatory drugs beyond the 34th week of gestation is theoretically associated with premature closure of the fetal ductus arteriosus due to the inhibition of cyclooxygenase. Inadvertent exposure to tiaprofenic exposure in the first trimester is of concern due to the paucity of prospective human data. Experiential data are limited to retrospective reports submitted to the manufacturer and animal data, the extrapolation of which to humans is very inaccurate. We report pregnancy outcome in 12 women who voluntarily contacted the Motherisk Program in Toronto about first trimester exposure to tiaprofenic acid. These women were older than women who generally contact Motherisk (30.6 years +/- 3.9 years versus 29.9 years +/- 3 years). Three pregnancies ended in first trimester miscarriages and one woman elected to terminate her pregnancy. Of the eight live births, the mean gestational age at delivery was 39.2 weeks +/- 2 weeks, the mean birthweight was 3359 +/- 503 gm, no malformations were detected, and age of attainment of developmental milestones was normal. Although 25% of exposed cases ended in miscarriages, this may not be statistically meaningful. However, a similar trend is documented in animal studies and should be borne in mind when counseling the pregnant patient.
This study aimed to assess the relationships between the scores of subjective assessment (metamemory) and those of performance testing for memory, on the one hand, and the level of depression, on the other. A hundred and eighty elderly subjects (102 women and 78 men; mean age 65.7 years) were selected for the study. They showed neither intellectual impairment (as assessed through Mini Mental State test: MMS) nor neuropsychiatric symptoms. Each subject was administered the Randt Memory Test (RMT) for performance testing, the Sehulster Memory Scale (SMS) for the subjective assessment, and the Geriatric Depression Scale (GDS). A MULTCOVA analysis showed that both age and the depression level are negatively correlated with both the measures (Acquisition-Recall: AR; Delayed Memory: DM) of the RMT. The scores of the second (memory complaints) of the three sets of SMS were positively correlated with those of AR and DM indices. A Multivariate Regression Analysis showed that in males age and the depression level were significant regressors for both AR and MD scores while in females only the depression level was a significant regressor for AR and only age was a significant regressor for DM. Our results suggest that a) the relationships between the depression level and memory functioning are close, although not fully homogeneous in men and women; and b) that the scores in some areas of metamemory parallel, independently of the level of depression, the performance outcomes of memory functioning.
This study aimed to assess the relationships among depression level, memory and metamemory scores on a large sample of elderly subjects (139 men and 147 women). Preliminary examination showed that none of the sampled subjects had intellectual impairment (as assessed by means of the Mini-Mental State Examination) or neuropsychiatric symptoms. Each subject was administered the Randt Memory Test (RMT), the Sehulster Memory Scale (SMS) and the Geriatric Depression Scale (GDS). A Multivariate Analysis of Covariance revealed a negative influence of depression on the two RMT measures (Acquisition-Recall: AR; Delayed Memory: DM) and on the three SMS measures (Set1: self-comparison; Set2: memory complaints; Set3: peer comparison), and of age on AR and DM, and Set1 and Set2. A Multivariate Regression Analysis showed that DM scores were positively correlated with Set2 in men and women, and with Set1 in women and Set3 in men, whereas AR scores related to Set2 and Set3 in men and Set1 in women. In addition, depression influenced negatively Set1, Set2 and AR scores in both men and women and DM scores only in men. On the whole, the results suggest that depression, memory and metamemory are rather closely related in non-severely depressed older individuals, albeit with slightly different patterns in men and women, and that some areas of metamemory are congruent with objective functioning regardless of the level of depressive symptoms.
Griffith psychometric test has been experimented on a group of 20 healthy newborn infants, monitored during their 1st year of life with quarterly check-ups. It was clear that the development general rates were constantly higher than the original values reported by the English author. In particular, in 12 months old infants, the rates appeared significantly higher than the rates observed on the same Italian specimen in past periods. A transverse and longitudinal study of the psychomotor development of subjects included in the specimen has given the opportunity to verify some of his features. The development outlines, traced by employing the average rates relevant to the 5 different aspects monitored (motor, personal-social, language, eye-hand co-ordination, practical reasoning), appeared to be well-balanced, that is without dissynchronisms between the different scales. The only exception being the scale of the social behaviour, were the average rates appear to be sensibly higher at every age. Individual development outlines, on the contrary, appeared to be disjointed in all aspects (except for 4 cases). In the longitudinal analysis then, some noteworthy oscillations in both general and partial rates, were observed among the controls carried out in subsequent periods in all the subjects.