PubMed Health⌕ Search

Biomedical subjects

C Marra

Publications and source records attributed to C Marra.

At least 19 recordsLinked to original sources

In vivo cholinergic circuit evaluation in frontotemporal and Alzheimer dementias.

The test of short latency afferent inhibition (SAI) of the motor cortex is helpful in demonstrating dysfunction of central cholinergic circuits in Alzheimer disease (AD). The authors evaluated SAI in 20 patients with frontotemporal dementia (FTD) and compared data with those from 20 patients with AD and 20 controls. SAI was normal in FTD, whereas it was reduced in AD. SAI may represent an additional tool to discriminate FTD from AD.

Afferent Pathways↗

Apolipoprotein E epsilon4 allele differentiates the clinical response to donepezil in Alzheimer's disease.

The existence of an association between apolipoprotein E (APOE) and Alzheimer's disease (AD) has been reported in several studies. The possession of an ApoE epsilon4 allele is now considered a genetic risk factor for sporadic AD. There has been a growing agreement about the role exerted by the ApoE epsilon4 allele on the neuropsychological profile and the rate of cognitive decline in AD patients. However, a more controversial issue remains about a possible influence of the APOE genotype on acetylcholinesterase inhibitor therapy response in AD patients. In order to address this issue, 81 patients diagnosed as having probable AD were evaluated by a complete neuropsychological test battery at the time of diagnosis (baseline) and after 12-16 months (retest). Patients were divided into two subgroups: (1) treated with donepezil at a dose of 5 mg once a day (n = 41) and (2) untreated (n = 40). Donepezil therapy was started after baseline evaluation. The APOE genotype was determined according to standardized procedures. We evaluated the possible effect of the APOE genotype on the neuropsychological tasks in relation to donepezil therapy. The statistical analysis of the results showed a global worsening of cognitive performances for all AD patients at the retest. Differences in the clinical outcome were analysed in the four subgroups of AD patients for each neuropsychological task. ApoE epsilon4 carriers/treated patients had improved or unchanged scores at retest evaluation for the following tasks: visual and verbal memory, visual attention and inductive reasoning and Mini Mental State Examination. These results indicate an effect of donepezil on specific cognitive domains (attention and memory) in the ApoE epsilon4 carriers with AD. This might suggest an early identification of AD patients carrying at least one epsilon4 allele as responders to donepezil therapy.

Aged↗

Retrospective analysis of variables favouring good surgical outcome in posterior epilepsies.

AIM: to determine variables favouring good surgical outcome in posterior epilepsies. METHODS: Fourteen patients submitted to epilepsy surgery were included in the study. The epileptogenic zone was located in temporo-parieto-occipital areas as assessed by both invasive and non-invasive pre-surgical evaluation. Several variables (age at first seizure; age at surgery; disease duration; type, frequency and clinical semiology of seizures; presence of lesion; scalp ictal and interictal EEG; localization and extension of epileptogenic zone; completeness of surgical resection) were compared (Fisher's exact test) with freedom from seizures to determine whether surgical outcome (Engel's classification) could be related to any of them. RESULTS: Seven patients were seizure free (Ia) and very satisfying results were obtained for 3 patients (2 Ib, 1 Ic). New post-surgical visual deficits occurred only in 3 patients. Surgical outcome was related significantly to two variables: scalp ictal EEG (focal versus non-focal; p: 0.014) and completeness of surgical resection of epileptogenic zone (p: 0.0023). A significant trend towards a better outcome for focal interictal intracranial activity versus a non-focal one (p: 0.07) was found. CONCLUSIONS: The correlation between completeness of epileptogenic zone resection and surgical outcome suggests that a presurgical protocol, allowing a precise definition of the area of resection, could help in obtaining more satisfying results in posterior epilepsies.

Adolescent↗

Neurophysiological predictors of long term response to AChE inhibitors in AD patients.

BACKGROUND: In vivo evaluation of cholinergic circuits of the human brain has recently been introduced using a transcranial magnetic stimulation (TMS) protocol based on coupling peripheral nerve stimulation with motor cortex TMS (short latency afferent inhibition, SAI). SAI is reduced in Alzheimer's disease (AD) and drugs enhancing cholinergic transmission increase SAI. METHODS: We evaluated whether SAI testing, together with SAI test-retest, after a single dose of the acetylcholinesterase (AChE) inhibitor rivastigmine, might be useful in predicting the response after 1 year treatment with rivastigmine in 16 AD patients. RESULTS: Fourteen AD patients had pathologically reduced SAI. SAI was increased after administration of a single oral dose of rivastigmine in AD patients with abnormal baseline SAI, but individual responses to rivastigmine varied widely, with SAI change ranging from an increase in inhibition of approximately 50% of test size to no change. Baseline SAI and the increase in SAI after a single dose of rivastigmine were correlated with response to long term treatment. A normal SAI in baseline conditions, or an abnormal SAI in baseline conditions that was not greatly increased by a single oral dose of rivastigmine, were invariably associated with poor response to long term treatment, while an abnormal SAI in baseline conditions in conjunction with a large increase in SAI after a single dose of rivastigmine was associated with good response to long term treatment in most of the patients. CONCLUSIONS: Evaluation of SAI may be useful for identifying AD patients likely to respond to treatment with AChE inhibitors.

Aged↗

The role of brain infarcts and hippocampal atrophy in subcortical ischaemic vascular dementia.

We investigated if, in patients with vascular lesions, the variable that best discriminated demented from non-demented patients was the severity of the vascular pathology or the degree of hippocampal atrophy. A total of 39 patients multiple subcortical infarcts, who could be considered as possible vascular dementia with small vessel pathology, with underwent a neuropsychological study and brain magnetic resonance imaging (MRI) DSM IV criteria supported by neuropsychological data were used to distinguish demented from non-demented patients. The MRI study took into account the degree of hippocampal atrophy (hippocampal height and interuncal distance) and the severity of vascular pathology (number of brain infarcts). The distribution of lesions and a factor analysis showed that hippocampal atrophy is a better predictor of dementia than the number of brain infarcts. Multiple subcortical infarcts alone are probably not able to cause clinical dementia but the presence of vascular lesions increases the expression of concomitant Alzheimer's disease.

Aged↗

Midterm results of a prospective randomized comparison of two different rabbit-antithymocyte globulin induction therapies after heart transplantation.

This prospective randomized study compared the effects in heart transplant recipients of thymoglobulin and ATG, two rabbit polyclonal antithymocyte antibodies available for induction therapy. Among 40 patients (29 men and 11 women, mean age: 40.7 +/- 14 years) undergoing orthotopic heart transplantation, 20 were randomly allocated to receive induction with thymoglobulin (group A) and 20 to ATG-fresenius (group B). Comparisons between the two groups included early posttransplant (6 months) incidence of acute rejection episodes (grade >/= 1B), bouts of steroid-resistant rejection, time to first rejection, survival, graft atherosclerosis, infections, and malignancies. The study groups displayed similar preoperative and demographic variables. No significant difference was found with regard to actuarial survival (P =.98), freedom from rejection (P =.68), number of early rejections > 1B (P =.67), mean time to first early cardiac rejection (P =.13), number of steroid-resistant rejections (P =.69). Cytomegalovirus reactivations were more frequent among group A (65%) than group B (30%; P =.028). New infections due to cytomegalovirus occurred only in group A (four patients; 20%; P =.05). No cases of malignancies were observed at a mean follow-up of 32.8 +/- 8.9 months. Although thymoglobulin and ATG showed equivalent efficacy for rejection prevention, they have different immunological properties. In particular, thymoglobulin seems to be associated with a significantly higher incidence of cytomegalovirus disease/reactivation.

Adult↗

Efficacy and limitations of preemptive therapy against cytomegalovirus infections in heart transplant patients.

OBJECTIVES: Cytomegalovirus (CMV) disease often represents a serious complication that promotes opportunistic infections in heart transplant recipients. In this study we evaluated the impact of preemptive gancylovir therapy, guided by pp65 antigenemia on the morbidity associated with viral reactivation. PATIENTS AND METHODS: We have performed a CMV infection surveillance program since March 1999, with antigenemia pp65 determinations weekly for the first 2 months biweekly in the third months, and monthly to the sixth month. Patients with pp65 antigenemia value >/= 10 positive cells per 2 x 10(5) polymorphonuclear cells (PMN) were treated with intravenous gancyclovir followed by 1 month of oral gancyclovir. RESULTS: Among the 107 patients who underwent the virological monitoring, 80 were pp65 antigenemia-positive with preemptive therapy administered in 48 cases. Five patients displayed symptomatic CMV disease (4.7% vs 18% rate in the period of 1988 to 1998 before the introduction of virologic monitoring; P <.01). We observed only one case of gancyclovir-resistant pneumonia which was successfully treated with foscarnet. CMV recurrence in 10 patients required a second cycle of gancyclovir treatment. Our experience included 13 opportunistic infections (12.7%) with 11 antigenemia-positive. CONCLUSIONS: Preemptive therapy drastically reduces the incidence of CMV disease and the associated morbidity. Compared to universal prophylaxis, this approach may avoid unnecessary pharmacologic treatment in more than 50% of transplant recipients. Indeed, preemptive therapy does not fully prevent CMV disease, because it may manifest at the first antigenemia determination, and furthermore may select gancyclovir-resistant strains.

Antigens, Viral↗

Motor cortex hyperexcitability to transcranial magnetic stimulation in Alzheimer's disease.

OBJECTIVES: Recent transcranial magnetic stimulation (TMS) studies demonstrate that motor cortex excitability is increased in Alzheimer's disease (AD) and that intracortical inhibitory phenomena are impaired. The aim of the present study was to determine whether hyperexcitability is due to the impairment of intracortical inhibitory circuits or to an independent abnormality of excitatory circuits. METHODS: We assessed the excitability of the motor cortex with TMS in 28 patients with AD using several TMS paradigms and compared the data of cortical excitability (evaluated by measuring resting motor threshold) with the amount of motor cortex disinhibition as evaluated using the test for motor cortex cholinergic inhibition (short latency afferent inhibition) and GABAergic inhibition (short latency intracortical inhibition). The data in AD patients were also compared with that from 12 age matched healthy individuals. RESULTS: The mean resting motor threshold was significantly lower in AD patients than in controls. The amount of short latency afferent inhibition was significantly smaller in AD patients than in normal controls. There was also a tendency for AD patients to have less pronounced short latency intracortical inhibition than controls, but this difference was not significant. There was no correlation between resting motor threshold and measures of either short latency afferent or intracortical inhibition (r = -0.19 and 0.18 respectively, NS). In 14 AD patients the electrophysiological study was repeated after a single oral dose of the cholinesterase inhibitor rivastigmine. Resting motor threshold was not significantly modified by the administration of rivastigmine. In contrast, short latency afferent inhibition from the median nerve was significantly increased by the administration of rivastigmine. CONCLUSIONS: The change in threshold did not seem to correlate with dysfunction of inhibitory intracortical cholinergic and GABAergic circuits, nor with the central cholinergic activity. We propose that the hyperexcitability of the motor cortex is caused by an abnormality of intracortical excitatory circuits.

Afferent Pathways↗

Noninvasive in vivo assessment of cholinergic cortical circuits in AD using transcranial magnetic stimulation.

BACKGROUND: A recently devised test of motor cortex excitability (short latency afferent inhibition) was shown to be sensitive to the blockade of muscarinic acetylcholine receptors in healthy subjects. The authors used this test to assess cholinergic transmission in the motor cortex of patients with AD. METHODS: The authors evaluated short latency afferent inhibition in 15 patients with AD and compared the data with those of 12 age-matched healthy controls. RESULTS: Afferent inhibition was reduced in the patients (mean responses +/- SD reduced to 85.7% +/- 15.8% of the test size) compared with controls (mean responses +/- SD reduced to 45.3% +/- 16.2% of the test size; p < 0.001, unpaired t-test). Administration of a single oral dose of rivastigmine improved afferent inhibition in a subgroup of six patients. CONCLUSIONS: The findings suggest that this method can be used as a noninvasive test of cholinergic pathways in AD. Future studies are required to evaluate whether short latency afferent inhibition measurements have any consistent clinical correlates.

Aged↗

Coronary artery bypass grafting in patients with severe left ventricular dysfunction: a prospective randomized study on the timing of perioperative intraaortic balloon pump support.

In this prospective trial the results of preoperative and intraoperative IABP in coronary artery bypass graft (CABG) patients with low left ventricular ejection fraction (LVEF) were compared. Sixty CABG patients with preoperative LVEF < or = 0.30 were enrolled: in group A patients (n=30) IABP was started within 2 hours preoperatively; in group B (n=30) it was instituted intraoperatively before weaning from cardiopulmonary bypass. Cardiac performance was assessed through Swan-Ganz catheter monitoring and daily echocardiography. Hospital survival, length of IABP support, intubation, ICU and hospital stay, need for postoperative inotropic drugs and incidence of myocardial infarction were compared between the two groups. Survival in group A patients proved significantly higher (P=0.047). Cardiac performance after myocardial revascularization improved in both groups with significantly better outcomes in group A patients (P<0.001). Doses of inotropic drugs (dobutamine, enoximone) were lower in group A (P=0.001; P=0.004) and duration shorter (P<0.001; P<0.001). No major IABP-related complication was observed.

Adult↗

Treatment of locally recurrent rectal cancer.

PURPOSE: This study was designed to analyze the outcome for patients with isolated local recurrence after radical treatment of rectal cancer and to identify predictors of curative resection. METHODS: The medical records of 87 patients who developed isolated local recurrence after curative radical surgery for primary rectal cancer were retrospectively reviewed. Survival rates from the time of recurrence were calculated using the Kaplan-Meier method. Tumor stage and histology, patient characteristics, and treatment variables were analyzed using logistic regression to identify predictors of curative surgery. RESULTS: Symptomatic treatment alone or chemotherapy and/or radiation therapy was provided to 23 patients (26 percent), and surgical exploration was performed in 64 patients. In 22 patients (25 percent), the tumor was considered unresectable at surgery (n = 13) or was resected for palliation with gross or microscopic positive margins (n = 9). In 42 patients (48 percent), curative-intent resection was performed. The only independent predictors of resectability were younger age at diagnosis, earlier stage of the primary tumor, and initial treatment by sphincter-saving procedure. There was no difference in survival between patients who had no surgery and those who had palliative surgery. The estimated five-year survival rate for patients who had curative-intent resection was better than for those who had no surgery or palliative surgery (35 vs. 7 percent; P = 0.01). Of the 42 patients who underwent curative-intent resection, 14 (33 percent) developed a second recurrence at a mean of 15 +/- 11 months after reoperation. Twenty-five percent of patients developed major complications. CONCLUSIONS: Salvage surgery for locally recurrent rectal cancer may be helpful in a selected group of patients. The stage and treatment of the primary tumor may help to identify patients with the best chance for curative-intent resection.

Chi-Square Distribution↗

Asymmetric medial degeneration of the intrapericardial aorta in aortic valve disease.

BACKGROUND: A geometrical and functional asymmetry in the normal aortic root has been recently demonstrated. Whether the distribution of medial degeneration (MD) within the wall of the dilated ascending aorta in adult patients reflects such asymmetry, still has to be assessed. METHODS: Nineteen patients with fibrocalcific aortic valve disease and dilatation of the intrapericardial aorta, without clinical signs and familiar history of primary elastic connective tissue disorders, underwent surgery. Biopsies (57 specimens) were taken in each patient from three areas of the ascending aortic wall distal to the three sinuses of Valsalva. MD lesions found at histology in each specimen were classified in three degrees. Comparisons were made between the three sites as to distribution of the three degrees and between one site and the other two as to incidence of the highest degree. RESULTS: A mild degree of MD was found in 26 specimens (45.6%), moderate in 14 (24.6%), severe in 17 (29.8%). The distribution of the three degrees of MD changes was significantly different between one of the three studied wall areas and the other two (P<0.001): a significantly greater incidence of the highest degree of involvement in the aortic wall distal to the non-coronary sinus than in the wall areas corresponding to the coronary sinuses was found (P<0.001). CONCLUSIONS: MD lesions in dilated intrapericardial aorta are more severe in the wall area distal to the non-coronary sinus, likely due to haemodynamic stress asymmetry.

Adult↗

Deep sternal wound infection: the role of early debridement surgery.

OBJECTIVE: This retrospective chart review study aimed to evaluate whether a more aggressive staged approach can reduce morbidity and mortality following post-cardiotomy deep sternal wound infection. METHODS: Between 1979 and 2000, 14620 patients underwent open heart surgery: mediastinitis developed in 124 patients (0.85%). Patients were divided in two groups: in 62 patients (Group A) (1979-1994) an initial attempt of conservative antibiotic therapy was the rule followed by surgical approach in case of failure; in 62 patients (Group B) (1995-2000) the treatment was staged in three phases: (1) wound debridement, removal of wires and sutures, closed irrigation for 10 days; (2) in case of failure open dressing with sugar and hyperbaric therapy (11 patients, 17%); (3) delayed healing and negative wound cultures mandated plastic reconstruction (three patients, 4%). Categorical values were compared using the Chi-square test, continuous data were compared by unpaired t-test. RESULTS: Incidence of mediastinitis was higher in Group B (62 out of 5535; 1.3%) than in Group A (62 out of 9085; 0.7%) (P=0.007). Mean interval between diagnosis and treatment was shorter in Group B (18+/-6 days) than in group A (38+/-7 days) (P=0.001). Hospital mortality was higher in Group A (19/62; 31%) than in Group B (1 out of 62; 1.6%) (P<0.001). Hospital stay was shorter in Group B (30.5+/-3 days) than in group A (44+/-9 days) (P=0.001). In Group B complete healing was observed in all the 61 survivors: 47 cases (76%) after Stage 1; 11 (18%) after Stage 2; three (4.8%) after Stage 3. CONCLUSIONS: Although partially biased by the fact that the two compared groups draw back to different decades, this study showed that an aggressive therapeutic protocol can significantly reduce morbidity and mortality of deep sternal wound infection.

Cardiac Surgical Procedures↗

The National NeuroAIDS Tissue Consortium: a new paradigm in brain banking with an emphasis on infectious disease.

The National NeuroAIDS Tissue Consortium (NNTC) was founded in 1998, in response to the scientific need for well-characterized central nervous system (CNS) and peripheral nervous system (PNS) tissues and fluids from HIV-infected individuals. In addition to performing the routine functions of non-transplant anatomic tissue banks, the Consortium offers a unique model for the integration of independent research entities in order to provide well-characterized tissues and fluids for the international research community. Herein, we describe the structure of the Consortium, pointing out the inherent strengths of linking together multiple independent sites for the purpose of banking HIV-infected nervous system tissues. We describe the neuropathology protocol that was adopted and successfully implemented at the four participating banks of the Consortium.

AIDS Dementia Complex↗

A double dissociation between accuracy and time of execution on attentional tasks in Alzheimer's disease and multi-infarct dementia.

Two cancellation/attentional tasks: (i) Lines Cancellation (LC) and Multiple Features Targets Cancellation (MFTC) and (ii) a standard battery of neuropsychological tests, the Mental Deterioration Battery (MDB), were administered to 68 patients with dementia of the Alzheimer's type (DAT) and 40 patients with multi-infarct dementia (MID), who were accurately matched for the overall severity of dementia, and to 40 normal controls. Both accuracy and time of execution were considered in evaluating performance on the two cancellation tasks, which involved visuospatial exploration and psychomotor speed, but were differently demanding in terms of selective attention. On the first cancellation task (LC), requiring a lower attentional load, the two demented patient groups performed at the same level of accuracy. On the second cancellation task (MFTC), which was more demanding in terms of selective and divided attention, DAT patients were significantly less accurate than MID patients, making a higher number of 'false-alarm' errors. Conversely, the time employed in the execution of both LC and MFTC took longer for MID than for DAT patients, suggesting a greater impairment of psychomotor speed in MID. In the MDB, DAT patients scored significantly worse than MID patients on several measures of episodic memory (the immediate recall, delayed recall and delayed recognition of Rey's Auditory Verbal Learning Test) and on a test of visual-spatial memory. These data suggest that, while psychomotor speed and the lower (sensorimotor) levels of attention are preferentially impaired in subcortical forms of dementia such as MID, the higher levels of selective and divided attention are more markedly disrupted in the Alzheimer type of dementia.

Aged↗

Brain perfusion abnormalities in Alzheimer's disease: comparison between patients with focal temporal lobe dysfunction and patients with diffuse cognitive impairment.

OBJECTIVES: Patients with Alzheimer's disease (AD) showing a selective impairment of episodic and semantic memory have recently been classified as affected by focal temporal lobe dysfunction (FTLD) and considered as a distinct subgroup of patients affected by a particular form of AD. The aim was to compare the cerebral perfusion of patients with AD with FTLD and patients with AD with the more typical profile of diffuse cognitive impairment (dAD). METHODS: Ten patients with AD with FTLD, 14 patients with AD with dAD, and 12 normal controls were studied. All the 24 patients with AD underwent a complete neuropsychological assessment. SPECT examination with [(99m)Tc]-HMPAO, using a four head brain dedicated tomograph, was performed in patients and controls. Tracer uptake was quantified in 27 regions of interest (ROIs), including lateral and mesial temporal areas. Mean counts in the 27 ROIs of controls, patients with FTLD and those with dAD were compared using an ANOVA for repeated measures with Bonferroni's correction. A logistic regression analysis, followed by a receiver operating characteristic (ROC) analysis, was also applied to select SPECT patterns which significantly differentiated patients with FTLD and those with dAD. RESULTS: Two scintigraphic patterns of abnormalities, shaping a double dissociation between the FTLD and dAD groups, emerged: a bilateral mesial temporal hypoperfusion, characteristic of FTLD and a posterior parietal (and temporal parietal) hypoperfusion characteristic of patients with dAD. CONCLUSIONS: These scintigraphic findings provide further support to the hypothesis that FTLD is not a mere stage but a distinct anatomoclinical form of AD. The combination of neuropsychological tests and [(99m)Tc]-HMPAO SPECT may be very useful in identifying patients with FTLD from the wider group of patients with dAD. This issue is particularly worthwhile, as there is increasing evidence that patients with FTLD have a slower rate of cognitive decline.

Aged↗

Relation between depression after stroke, antidepressant therapy, and functional recovery.

The aim was to evaluate the effects of poststroke depression and antidepressant therapy on the improvement of motor scores and disability, to verify if the negative effects of poststroke depression on functional recovery could be counterbalanced by taking antidepressant drugs. RESULTS OBTAINED BEFORE, DURING, AND AFTER REHABILITATION: On the Barthel index, Canadian neurological scale, and Rivermead mobility index-by 49 depressed patients with stroke, who had been treated (n=25) or not treated (n=24) according to the different therapeutic approaches of their physicians, were compared with results similarly obtained by 15 non-depressed patients with stroke. Analysis was by multivariate analysis of variance for repeated measures There was a non-significant difference between the groups in their motor and functional scores, and a significant improvement on time. A significant interaction between group and time was seen. This interaction was particularly significant on the Rivermead mobility index, and was due to the fact that the recovery of non-treated depressed patients with stroke was less than the non-depressed and the depressed but treated patients with stroke. Furthermore, recovery from depression was significantly greater in treated than in non-treated depressed patients with stroke. In conclusion, poststroke depression has negative effects on functional recovery, and a pharmacological treatment of depression can counterbalance this effect.

Aged↗