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Biomedical subjects

C Marra

Publications and source records attributed to C Marra.

At least 55 records · Page 3Linked to original sources

Verbal memory impairment in COPD: its mechanisms and clinical relevance.

STUDY OBJECTIVES: Identification of mechanisms accounting for verbal memory impairment in patients with severe COPD; assessing the relationship between verbal memory and the overall cognitive performance; verifying if verbal memory impairment affects medication adherence. DESIGN: Case-comparison study. SETTING: Outpatient Departments of Pneumology and Neurology, Day Hospital of General Surgery. PATIENTS: Forty-two COPD ambulatory patients, age 70+/-9.7 years, with hypoxemia and hypercarbia (group A); 27 normal subjects of comparable age and educational level (group B); 31 patients with Alzheimer's disease (group C); and 26 older normal subjects (group D). MEASUREMENTS AND RESULTS: The overall cognitive function and verbal memory were evaluated by the Mental Deterioration Battery and 14 indexes of verbal memory. Defective retrieval and recognition mechanisms distinguished group A from group B. According to discriminant analysis, verbal memory profile of COPD patients was group specific in 38.1% of cases and conformed to that of group B, C, and D in 19%, 16.7%, and 26.2% of cases, respectively. In COPD patients, both immediate and delayed recall, the strongest determinants of the discriminant function, were significantly correlated with the overall cognitive performance (rho=0.64, p=0.001; rho=0.61, p=0.001, respectively). Poor adherence to medication regimen was significantly associated with abnormal delayed recall score (82.3% vs 36% in subjects with normal delayed recall, p<0.008). CONCLUSIONS: Decline of verbal memory parallels that of the overall cognitive function in COPD patients and is due to the impairment of both active recall and passive recognition of learned material. It could be an important determinant of the level of medication adherence.

Aged↗

Role of the heart surgeon in the emergency treatment of diuretic resistant edema in grades III-IV heart failure.

Acute or chronic valvular diseases, acute myocardial infarction and its complications, dilated cardiomyopathies, all may became the cause of heart failure leading to different degrees of cardiogenic edema. Today cardiac failure is treated from its the early stage by medical and/or surgical therapy. Thereafter, in a small population of patients, heart failure may became unresponsive to any kind of standard medical treatment. Conventional surgical procedures are often inadequate and carry a high risk of perioperative mortality. This study analyzes the outcome of 139 patients with end-stage cardiomyopathy who underwent heart transplantation between January 1988 and October 1996. We found that patients transplanted while on severe decompensation are at a higher perioperative mortality due to irreversible multi-organ failure. The study also suggests that the implantation of a left ventricle assist device as a bridge to transplantation is a promising maneuver for the most severe patients.

Adolescent↗

Studies of flurbiprofen 4'-hydroxylation. Additional evidence suggesting the sole involvement of cytochrome P450 2C9.

Flurbiprofen, a non-steroidal anti-inflammatory drug (NSAID), is metabolized by both oxidation via the cytochrome P450 system and by glucuronidation. The major oxidative pathway in flurbiprofen metabolism is to a 4'-hydroxy metabolite, and recently we demonstrated that cytochrome P450 2C9 and its R144C variant were involved in this process (Tracy et al., Biochem Pharmacol 49: 1269-1275, 1995). Using complementary DNA (cDNA)-expressed cell systems, it has been demonstrated that at physiological concentrations of flurbiprofen there is a lack of involvement of P450s 1A2, 2C8, 2E1, and 3A4. In evaluating flurbiprofen as a potential probe for cytochrome P450 2C9, it is important to assess the involvement of additional P450s in this process. To this end, further studies were undertaken using specific inhibitors of P450 2C9 and P450 cDNA-expressed microsomes for P450 1A1, 2A6, 2B6, 2C19, and 2D6 to assess their potential involvement. We observed the inhibition of (R)- and (S)-flurbiprofen 4'-hydroxylation by an inhibitor of P450 2C9, sulfaphenazole (Ki = 0.07 and 0.06 microM, respectively), and the NSAID piroxicam (Ki = 10 and 7 microM, respectively). Furthermore, using microsomes from a lymphoblastoid cell line, we found that P450s 1A1, 2A6, 2B6, 2C19, and 2D6 were not involved in flurbiprofen hydroxylation at physiological concentrations of flurbiprofen. This finding is particularly important due to the sequence homology and potential substrate overlap of P450 2C9 and 2C19. These studies then provide additional evidence to suggest that P450 2C9 may be the only isoform involved to any substantial degree in flurbiprofen 4'-hydroxylation, and thus this reaction is useful as an in vitro probe for this particularly cytochrome P450 isoform and may be useful as an in vivo probe.

Anti-Inflammatory Agents, Non-Steroidal↗

Factors affecting recurrence in Crohn's disease. Results of a prospective audit.

It has been suggested that certain clinical and morphological features can modify the outcome of Crohn's disease, particularly regarding recurrence after surgery. A series of 233 patients was followed prospectively. They underwent a resectional surgical procedure for both primary and recurrent Crohn's disease during a fifteen-year period with a minimum follow-up of eighteen months. Possible risk factors for recurrence were studied. They included duration of disease before primary surgery, the type of clinical presentation at onset (whether "Perforating" or "Non-perforating"), the initial anatomical location, the presence of microscopic disease at the resection edges, the type of surgical procedure (anastomosis vs stoma), post-operative surgical complications and the age of the patient. The duration of the disease before the initial operation was the only significant factor related to the recurrence rate.

Adult↗

Some preliminary findings concerning a new scale for the assessment of depression and related symptoms in stroke patients.

The authors describe a new scale, the Post-Stroke Depression Rating Scale (PSDRS), specifically constructed to investigate the emotional, affective and vegetative disorders of stroke patients. They also report some preliminary data concerning the validity and reliability of the new scale and of its sections and the first results obtained administering the PSDRS to 68 stroke patients and 10 subjects affected by a "functional" form of major depression. The comparison between the results obtained on the PSDRS by patients classified (on the basis of DSM III diagnostic criteria) as having major depression of either vascular or functional origin seems to show an incomplete overlap between these two forms of depression. In patients classified as having major post-stroke depression, part of the symptomatology seems to be due either to the direct effect of the brain lesion or to the psychological reaction of the patient to the disabilities and handicaps provoked by the lesion.

Cerebrovascular Disorders↗

Effects of aging and of Alzheimer's disease on verbal memory.

This study aimed to define the verbal memory profiles of very old normal subjects and subjects with Alzheimer's Disease, and to identify verbal memory indices having the highest discriminant power. Forty-three old normal subjects (mean age = 71 years, SD = 3, range = 65-75), 39 very old normal subjects (mean age = 81 years, SD = 4, range = 76-87), and 45 Alzheimer's patients (mean age = 70 years, SD = 5, range = 59-78) received the Rey test of verbal memory and the WAIS-R Digit Span forward and backward. All but one of the indices could distinguish very old from Alzheimer's subjects. A discriminant analysis disclosed a verbal memory profile of Alzheimer type in 15.4% of the very old group and of very old type in 16.2% of the Alzheimer's patients. Rate of forgetting, immediate and delayed Rey indices, and the true positive responses were, in decreasing order, the main determinants of the discriminant function. Thus, all of the components of verbal memory are differently affected by aging and Alzheimer's disease and contribute to define individual verbal memory profiles.

Aged↗

A prospective survey of knowledge and perceptions of ondansetron: what do health care workers know about this drug?

Ondansetron is a relatively new drug whose optimal use is dependent on an understanding of its characteristics and role relative to traditional antiemetics. To assess perceptions and knowledge regarding ondansetron, we conducted a prospective written survey involving 56 physicians, pharmacists, and nurses at this hospital. Pharmacists claimed to be exposed to ondansetron promotion by industry more than the other groups. Apart from industry, pharmacists were considered to be the most common source of drug information. Nurses were less aware of dosage form equivalence than the other groups (p = 0.042). Physicians were more aware of twice daily dosing efficacy than other respondents (p = 0.0006). Nurses were able to better identify the relative duration of antiemetic benefit over metoclopramide (p = 0.008); however, most participants tended to be misinformed on this issue. Pharmacists were more familiar with the side effect profile while physicians were more cognizant of oral (p = 0.001) and parenteral (p = 0.018) drug costs than other groups. Overall, survey scores for physicians and pharmacists were higher than those for nurses (p = 0.007). There is an apparent difference across health care profession disciplines in the perceptions and knowledge about ondansetron. Specific misconceptions could lead to suboptimal drug use and warrant efforts to ensure a good understanding of the attributes and relative role of this agent.

Antiemetics↗

Some aspects of memory disorders clearly distinguish dementia of the Alzheimer's type from depressive pseudo-dementia.

Two groups of patients affected by mild dementia of the Alzheimer's type (n = 42) or by depressive pseudo-dementia (n = 26) were given a modified version of the Rey's Auditory Verbal Learning Test. The two groups were roughly matched for overall level of cognitive impairment. The main purpose of the research was to determine if some aspects of their memory disorders distinguished the two diagnostic groups. Comparison between results obtained on recall and on recognition measures was of little diagnostic usefulness in distinguishing dementia of the Alzheimer's type (DAT) from depressive pseudo-dementia (DPD). A marked prevalence of the recency over the primary effect in immediate recall, a high rate of forgetting, and the presence of many intrusion errors on delayed recall were observed more frequently in DAT than in DPD patients. None of these indices, however, was sensitive and specific enough to allow a confident diagnostic discrimination at the individual case level. The memory measure which best distinguished DAT from DPD patients was the presence of several false positive errors on delayed recognition because DAT patients adopted a very liberal response bias, endorsing many false recognition errors, whereas DPD patients adopted a conservative criterion and tended to miss real stimuli, rather than making false recognition errors.

Aged↗

Neuropsychological abnormalities in AIDS and asymptomatic HIV seropositive patients.

Neuropsychological and immunological parameters were studied in 36 AIDS patients with early disease and without clinical, laboratory, and neuroradiological signs of CNS impairment, and also in 33 asymptomatic HIV seropositive subjects. Many AIDS patients performed abnormally on timed psychomotor tasks, tasks involving sequencing and "set-shifting", and memory tasks stressing attention, learning, active retrieval, and monitoring of information. Asymptomatic HIV seropositive subjects as a group did not perform significantly worse than controls. However, on the basis of a cut off number of pathological performances on neuropsychological tasks, 52.8% of AIDS and 30.3% of asymptomatic HIV seropositive subjects had cognitive impairment, compared with 3.9% of HIV seronegative controls. Low values of CD4+ cells and of CD4+/CD8+ ratio and high titres of P-24 antigen in the blood prevailed among subjects with cognitive impairment, especially in the asymptomatic HIV seropositive group.

Acquired Immunodeficiency Syndrome↗

Chronic obstructive pulmonary disease. An original model of cognitive decline.

In order to characterize the neuropsychologic profile of patients with hypoxic-hypercapnic chronic obstructive pulmonary disease (COPD), the performance of 36 patients with COPD 69 +/- 10 yr of age (mean +/- SD) on 19 tests exploring eight cognitive domains was compared with those of 29 normal adults (69 +/- 7 yr of age), 20 normal elderly adults (78 +/- 2 yr of age), 26 patients with Alzheimer-type dementia (72 +/- 6 yr of age), and 28 with multi-infarct dementia (MID) (70 +/- 8 yr of age). The discriminant analysis of cognitive test scores showed that 48.5% of patients with COPD had a specific pattern of cognitive deterioration characterized by a dramatic impairment in verbal and verbal memory tasks, well-preserved visual attention, and diffuse worsening of the other functions. The remaining patients with COPD were functionally classified as normal adults (12.1%), normal elderly adults (15.2%), those with MID (12.1%), and those with Alzheimer-type dementia (12.1%) according to discriminant analysis. Cognitive impairment was significantly and positively correlated with age (p < 0.05) and duration of hypoxic-hypercapnic chronic respiratory failure (p < 0.05). Because patients with COPD were receiving oxygen therapy from the beginning of oxyhemoglobin desaturation, results suggest that continuous oxygen therapy does not prevent or only partly prevents cognitive decline in COPD. Although some analogies between age-related and COPD-related cognitive decline are evident, a distinct cognitive profile was found in a large fraction of patients with COPD and it differs in several aspects from those of both normal and demented subjects.

Aged↗

Cognitive risk factors and neuropsychological performance in HIV infection.

Almost all investigations examining the effects of early HIV infection on neuropsychological functioning in homosexual males have excluded subjects with cognitive risk factors such as recreational drug use and head injury. While insuring that results reflect the influence of the virus on cognition, this selection bias limits the ability to generalize findings. Comprehensive neuropsychological evaluations were compared between two groups of homosexual males with a variety of cognitive risk factors. Subjects were 132 HIV seropositive males (108 CDC class II & III and 24 CDC class IVA & IVC2) and 65 HIV seronegative controls. Recreational drug use in the six months prior to exam was found to interact with HIV infection and was associated with selective areas of cognitive decline and a significantly worse overall neuropsychological performance. Although significantly lower functioning in the domains of Verbal Memory and Attention and Speed of Information processing was noted for subjects with CDC class IVA and IVC2 compared to seropositives with CDC class II & III, overall neuropsychological performance was similar in these two groups. At this early stage of HIV infection, we did not find indication of association between neuropsychological performance and decreased immunological status. A history of head injury and recent recreational drug use emerged as primary cognitive risk factors associated with decreased neuropsychological performance. As 50% of our HIV seropositive subjects reported active recreational drug use, this cognitive risk factor in particular may contribute to the appearance of HIV-related cognitive deficits during early stages of HIV infection.

Cognition Disorders↗

Unrecognized dementia: sociodemographic correlates.

Eighteen geriatric patients, aged 77 +/- 8 years, in whom a diagnosis of dementia was formulated during an unrelated hospital stay, were studied to clarify why dementia had not been detected at an earlier stage. The control group was composed of 20 patients aged 79 +/- 11 years with a comparable degree of cognitive impairment who had been recognized 1-3 years previously. The index group was characterized by a lower formal education (5.2 +/- 3.7 years vs 8.5 +/- 4.7 years, p < 0.05), and higher prevalence of subjects living in rural areas (50% vs 10%, p < 0.006); other sociodemographic variables (age, sex, marital status, employment before retirement) could not distinguish the groups. A multivariate logistic regression analysis showed that the end point late diagnosis was significantly correlated with the independent variables, rural residence (odds ratio = 4.65, C.I. = 1.7-12.9) and lower occupational role (odds ratio = 3.3, C.I. = 1.2-9.5). A structured interview with relatives of the patients disclosed 3 main reasons accounting for later diagnosis: poor awareness of the problem of dementia; respect for parents and grandparents; and negligible effect of this problem on family life and economy. In the control group, dementia had been diagnosed earlier mostly because of its heavier social and economic impact on the family.

Aged↗

Central nervous system manifestations in human immunodeficiency virus infection without AIDS.

To characterize neurological and neuropsychological findings associated with human immunodeficiency virus type-I (HIV) infection, 77 seropositive homosexual or bisexual males with no or minor symptoms of HIV were compared prospectively to 44 HIV seronegative men by observers blinded to serological status of the subjects. Neurological symptoms and examination findings were not significantly different between seropositives and seronegatives except for cranial nerve findings, predominantly mild hearing impairment. Mean performance scores for a 15-test neuropsychological battery were within an unimpaired range for both groups, although for five tests, mean scores were significantly poorer in seropositives. After adjustment for vocabulary score, and demographic and psychosocial variables, the mean score of seropositives was significantly worse only for the Benton Visual Retention Test. Magnetic resonance (MR) images of brain were abnormal in 14 (27%) of 52 seropositives and one of 10 seronegatives (value was not significant). HIV was isolated from cerebrospinal fluid (CSF) in 31 (61%) of 51 seropositives. The only clinical or laboratory difference between CSF culture positives and negatives was a higher CSF immunoglobulin synthesis rate in the former subjects (medians of 10.3 versus 0.1 mg/day; p = 0.03). An additional 13 seropositive subjects had immunologic evidence of central nervous system HIV infection, defined by a serum-to-CSF HIV antibody ratio of less than 5.5. Intracranial abnormalities on MR imaging were associated with CSF immunologic responses to HIV. Nervous system involvement occurred in the vast majority of men with early HIV infection, but clinically significant impairment was uncommon.

Adult↗

An experimental model of early central nervous system syphilis.

Although up to 40% of patients with early syphilis have evidence of central nervous system (CNS) invasion by Treponema pallidum, the pathogenesis of CNS syphilis is not understood. A rabbit model that mimics early CNS involvement in humans was developed and characterized. Mild cerebrospinal fluid pleocytosis was evident 2 weeks after intracisternal inoculation of T. pallidum and peaked at 9 weeks. The VDRL test in cerebrospinal fluid was reactive in 24% of animals, most commonly at 9 weeks after infection. T. pallidum could be isolated from the CNS of animals infected for 4, 6, or 9 weeks but not from animals infected for 12 or 20 weeks. Clinically, 6% of animals developed uveitis, similar to the frequency in patients with secondary syphilis. Thus, this model of meningeal and ocular syphilis seems to be analogous to the early CNS infection in humans and can be used for studies of pathogenesis and treatment.

Animals↗

Double dissociation between temporal and spatial pattern processing in patients with frontal and parietal damage.

One hundred and twenty nine patients affected by a cerebral lesion confined to a single lobe, underwent a battery of tests including the "Temporal Rule Induction" (TRI) and the Raven's "Coloured Progressive Matrices" (CPM). Frontal patients scored lower than any other group on TRI and parietal patients on CPM. This contrasting pattern of performance provides strong empirical support to the hypothesis that the frontal lobe is specifically involved in tasks that require a control on temporally ordered information whereas the parietal lobe is concerned with cognitive activities that imply visuo-spatial analysis.

Adult↗