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Biomedical subjects

L Bäckman

Publications and source records attributed to L Bäckman.

At least 19 recordsLinked to original sources

Endoluminal laser-Doppler measurements of jejunal perfusion in patients undergoing liver transplantation.

Patients undergoing liver transplantation are at risk of developing the multiple organ dysfunction syndrome, and attention has been focused on the pathogenic role of decreased gastro-intestinal mucosal perfusion. The aim of this study was to investigate the use of laser-Doppler flowmetry for determination of jejunal perfusion. In 10 patients an endoluminal laser-Doppler catheter was positioned with the tip in the jejunum for continuous measurements of jejunal perfusion. The anhepatic phase was associated with a progressive decrease in jejunal perfusion to 49 (40/65)% (P < 0.01) of dissection phase value. At the end of surgery the jejunal perfusion had increased to 134 (103/158)% (P < 0.01) of dissection phase jejunal perfusion. The endoluminal laser-Doppler technique was found to be easily applicable for continuous monitoring of jejunal perfusion, and the technique could prove valuable in detecting gastro-intestinal hypoperfusion in patients undergoing liver transplantation.

Adult↗

Stability of the preclinical episodic memory deficit in Alzheimer's disease.

We sought to determine the course of the preclinical episodic memory deficit in Alzheimer's disease. Using data from a population-based study, we compared persons who developed Alzheimer's disease n = 15) with persons who were non-demented n = 105) 6 and 3 years prior to the diagnosis of dementia. Participants were tested on tasks assessing episodic memory free recall and recognition of words) and short-term memory digit span). The incident Alzheimer's disease cases performed more poorly than their non-demented counterparts both 3 and 6 years before diagnosis on recall and recognition. There were no group differences in either forward or backward digit span. The selective impairment of episodic memory before the diagnosis of Alzheimer's disease is consistent with the view that early changes in the hippocampal complex play an important role in the memory deficit in preclinical Alzheimer's disease. On both preclinical measurement occasions, recall and recognition made independent contributions to group classification in logistic regression analyses. However, there was no evidence for accelerated decline of episodic memory in the incident Alzheimer's disease group from 6 to 3 years before diagnosis. These results indicate that Alzheimer's disease is characterized by a long preclinical period during which episodic memory deficits are detectable. The magnitude of these deficits appears to be quite stable, at least up to 3 years before diagnosis. This may reflect the fact that those biological events that eventually result in clinically diagnosed Alzheimer's disease e.g. the appearance of amyloid plaques and neurofibrillary tangles) accumulate at a relatively slow rate.

Aged↗

The course of cognitive impairment in preclinical Alzheimer disease: three- and 6-year follow-up of a population-based sample.

OBJECTIVES: To examine the ability of the total score and individual items from the Mini-Mental State Examination in predicting the development of Alzheimer disease (AD) across a 3- and 6-year period in a population-based sample, and to describe the longitudinal changes in these measures across the same follow-up periods. DESIGN: Prospective follow-up of a community-based cohort, with 3 times of testing across a 6-year period. At each time of measurement, participants were clinically examined by physicians to identify demented and nondemented participants according to Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, criteria. PARTICIPANTS: The study population consisted of all participants who were nondemented at the first follow-up and participated in the second follow-up examination. Among those, 459 remained nondemented and 73 developed AD during the second follow-up period. RESULTS: Baseline differences in the total Mini-Mental State Examination score and the delayed memory item were seen 6 years before eventual dementia diagnosis (P<.01). Analysis of the longitudinal changes showed no differences in the rate of decline for the incident AD or nondemented group between time 1 and time 2 (P>.10). However, the incident AD group exhibited precipitous declines in 8 of the 10 subscales between time 2 and time 3, the point at which they were clinically diagnosed (P<.01). Logistic regression analyses showed that only the delayed memory item was a significant predictor of who would develop AD, independent of age, sex, and years of education, at both of the first 2 times of measurement (P<.001). CONCLUSIONS: The diagnosis of AD is preceded by a long preclinical phase in which deficits in memory performance are most common. These deficits remain relatively stable up until the time that a dementia diagnosis can be rendered. Arch Neurol. 2000.

Aged↗

Daclizumab prevents acute rejection and improves patient survival post transplantation: 1 year pooled analysis.

Daclizumab is a genetically engineered human IgG1 monoclonal antibody specific for the alpha chain of the IL-2 receptor. A pooled analysis of two randomized, double-blind studies was performed on the efficacy and safety of daclizumab in renal transplantation, given in addition to standard immunosuppression. Patients receiving their first cadaveric renal allograft were randomized to receive 5 doses of daclizumab (n = 267) or placebo (n = 268), starting pre-operatively. Acute rejection at 1 year occurred less frequently with daclizumab (n = 74, 27.7 %) than with placebo (n = 116, 43.3%) (P = 0.0001). Fewer patients treated with daclizumab required anti-lymphocyte therapy for acute rejection (7.9 % vs. 15.3 %; P = 0.005). Mean cumulative doses of corticosteroids were lower with daclizumab (4133 mg) than with placebo (4562 mg). One year graft survival was 91.4 % with daclizumab, compared with 86.6 % on placebo (P = 0.065), with patient survival of 98.5 % and 95.1 % for daclizumab and placebo respectively (P = 0.022). Daclizumab was well tolerated. No increase in infectious episodes or lymphoproliferative disorders was observed with daclizumab. The incidence of cytomegalovirus infections was similar with daclizumab and placebo (15 % vs. 17.5 %). Therapy with daclizumab significantly reduces acute rejection in renal transplantation and improves patient survival without any increase in morbidity.

Adult↗

High suicidal ideation in persons testing for Huntington's disease.

This study examined the first participants who registered for the Huntington's disease predictive testing program 1990-1995 in Stockholm, Sweden. A psychosocial investigation was performed to evaluate potential effects of the presymptomatic testing. The results showed no significant differences between 13 gene carriers and 21 noncarriers in pretest attitudes, expectations, general well-being, life satisfaction and lifestyle, the need for support, estimated sense of wellbeing or degree of health. However, both groups showed high suicidal ideation and self-injurious behavior. Noncarriers had a very high frequency of attempted suicide, and both groups had similarly pronounced psychiatric dysfunction. Their relatives also had high frequencies of psychiatric diseases, suicide or suicidal attempts. Most of the participants had a desire to meet a psychologist or a social worker. The need for counseling, using a well designed protocol, and the importance of focusing on suicide risk of participants in predictive testing programs is emphasized.

Adult↗

Experiencing liver transplantation: a phenomenological approach.

In order to promote health, nurses and other health care professionals need to discover and articulate the meaning that is implicit in experiencing life after liver transplantation. From such an understanding, appropriate nursing interventions can be based. The aim of this study was to investigate the subjective experiences of the meaning of having a liver transplant, 1 year after the transplantation. After approval from the ethics committee at Goteborg University, 12 patients, nine women and three men, were interviewed. The study sample was chosen strategically to represent common diagnoses preceding liver transplantation. A phenomenological approach was chosen for the study. Analyses of the interviews were based on a modified version of a phenomenological method by Karlsson. Seven categories emerged: facing the inevitable; recapturing the body; emotional chaos; leaving the experts; family and friends; the threat of graft rejection; and honouring the donor. Having undergone a liver transplant meant living in a paradoxical situation. Knowing that you survived, it was a struggle to regain physical strength under great emotional stress. The recipients had to self-administer life-long medication, recognize symptoms indicating a potential problem and monitor for the possibility of graft rejection. Social support was essential for recovery. Meeting others with the same experience helped liver-transplanted patients to deal with their identity crises as well as undergo a transformation from being utterly unique to a survivor among others. The clinical implications from this study are that interventions, such as patient education, and social and mental support, are important tools to optimize both self-care capacity and the ability to maintain a healthy perception of identity after having a liver transplant at least up to 12 months post-transplant.

Activities of Daily Living↗

The relationship between signs of cardiovascular deficiency and cognitive performance in old age: a population-based study.

The influence of cardiovascular signs (CVS) on cognitive performance was examined in 227 older adults not suffering from dementia between 75 and 96 years of age who were sampled from the community. Participants received a comprehensive physical examination that included specific evaluation of current CVS, including dyspnea, cardiac murmur, and edema in lower limbs. They were administered tests of digit span, episodic recall and recognition, verbal fluency, and visuospatial skill. CVS were found to predict performance on tests of episodic memory and visuospatial skill, after the effects of age, education, gender, relevant drug use, and mood symptoms were controlled for. Although CVS accounted for relatively little general performance variation, the findings are relevant to the understanding of normal variation in late-life cognitive performance. Finally, CVS increased with age and accounted for a sizable proportion of the age-related cognitive variation.

Age Factors↗

Functional changes in brain activity during priming in Alzheimer's disease.

Patients with Alzheimer's disease (AD) are often impaired on certain forms of implicit memory, such as word-stem completion priming (WSCP). Lesion data suggest that deficient WSCP may be associated with abnormal functioning in the posterior neocortex. Using positron emission tomography (PET), we here provide direct support for this view. Compared with normal old adults, AD patients showed reduced priming on a word-stem completion task. The normal old showed decreased activity in right occipital cortex (area 19), whereas the AD patients showed increased activity in this region during priming. To the extent that decreased activity during priming reflects an experience-dependent reduction of the neuronal population involved, these results indicate that shaping of the relevant neurons is slower in AD, possibly as a result of inadequate initial stimulus-processing.

Adult↗

Age-related cognitive deficits mediated by changes in the striatal dopamine system.

OBJECTIVE: The study examined the influence of losses in dopaminergic function on age-related cognitive deficits. METHOD: Eleven healthy subjects (21-68 years of age) completed a set of cognitive tasks used to assess perceptual speed and episodic memory. D(2) receptor binding was measured in the caudate and the putamen by using positron emission tomography. RESULTS: A gradual age-related deterioration was found for all cognitive tasks and for D(2) binding in both striatal structures. Statistical control of D(2) binding eliminated the age-related cognitive variation, whereas residual effects of D(2) binding were seen after the analysis controlled for age. CONCLUSIONS: D(2) receptor binding is a more important factor than chronological age in accounting for variation in cognitive performance across the adult lifespan. Changes in dopaminergic neurotransmission play an important role in aging-related cognitive decline.

Adult↗

The occurrence of depressive symptoms in the preclinical phase of AD: a population-based study.

OBJECTIVE: To examine preclinical depressive symptoms 3 years before the diagnosis of AD. METHODS: The authors compared incident AD patients and nondemented individuals in terms of baseline mood- and motivation-related symptoms of depression, and assessed whether depressive symptoms in preclinical AD are related to self-perceived memory problems. Participants came from a population-based longitudinal study on aging and dementia in Stockholm, Sweden. The sample consisted of 222 persons older than 74 years who were followed for a 3-year interval. Thirty-four individuals had developed AD at follow-up, whereas 188 remained nondemented. Dementia diagnosis was made according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised. Depressive symptoms were assessed by the Comprehensive Psychopathological Rating Scale. RESULTS: The incident AD patients had more depressive symptoms than the nondemented persons at baseline. There was a dominance of motivation-related symptoms of depression (e.g., lack of interest, loss of energy, concentration difficulties) in preclinical AD. This association remained when adjusting for subjective memory complaints. CONCLUSIONS: Depressive symptoms are elevated preclinically in AD, and this elevation is not merely a by-product of self-perceived cognitive difficulties. Thus, depressive symptoms may be part of the preclinical phase in AD.

Aged↗

The influence of prolactin response to d-fenfluramine on executive functioning in major depression.

BACKGROUND: The main purpose of this study was to assess the influence of serotonergic activity, as measured by prolactin response to d-fenfluramine, on executive functioning in major depression. METHODS: Forty-one persons between 22 and 71 years of age who met the DSM-IV criteria for major depressive episode were administered the Wisconsin Card Sorting Test (WCST) in computerized format, and d-fenfluramine was administered orally. Postfenfluramine blood samples for ascertaining plasma prolactin levels were obtained. RESULTS: The key finding was that prolactin response was positively related to four out of five selected WCST variables. Also, increasing age was associated with decreasing WCST performance. There was no interaction between prolactin response and age, indicating that the effects of prolactin response on the WCST generalized across the age range examined. CONCLUSIONS: The overall pattern of results suggests that there may be a relationship between serotonergic activity and executive functioning in major depression.

Adult↗

Brain regions associated with episodic retrieval in normal aging and Alzheimer's disease.

OBJECTIVE: To examine patterns of brain activation during verbal episodic retrieval in normal elderly subjects and patients in an early phase of AD. BACKGROUND: It is established that 1) a profound episodic memory impairment is a cardinal symptom of AD; and 2) some of the earliest brain changes in this disease occur in regions critical to episodic memory, such as the hippocampus and neighboring regions. Yet, it remains largely unknown whether the episodic memory deficit seen in AD is paralleled by concomitant alterations in brain activity during actual task performance in these or other brain areas. METHODS: Using PET, blood flow was assessed in normal elderly subjects and patients with early AD during two retrieval conditions involving completion of word stems: baseline and cued recall. RESULTS: The patients with AD showed a marked performance deficit in cued recall, although the two groups were indistinguishable in the baseline task condition. Both groups showed bilateral activity in orbital and dorsolateral prefrontal cortex, left precuneus, and right cerebellum, as well as decreased activity in distinct left temporal regions during cued recall. The normal elderly alone activated the left parietal cortex and the left hippocampal formation during episodic retrieval. By contrast, AD-related increases in activity during cued recall were observed in the left orbital prefrontal cortex and left cerebellum. CONCLUSIONS: The similar patterns of activations in the two groups suggest that a large distributed network involved in episodic memory retrieval functions relatively normally in early AD. Those retrieval activations seen in the normal elderly, as opposed to the patients, may reflect AD-related failures in semantic processing and successful recollection of the target information, respectively. Finally, the AD-related increases in activity were interpreted in terms of compensatory reactions to the difficulties in performing the episodic memory task.

Aged↗

Further evidence on the effects of vitamin B12 and folate levels on episodic memory functioning: a population-based study of healthy very old adults.

BACKGROUND: The relationship between vitamin status and cognitive functioning has been addressed in several recent studies with inconclusive results. The purpose of this study was to examine separate and combined effects of serum vitamin B12 and folic acid on episodic memory functioning in very old age. METHODS: Four study groups were selected from a population-based sample of healthy very old adults (90-101 years of age): normal B12/normal folic acid, low B12/normal folic acid, normal B12/low folic acid, and low B12/low folic acid. Cutoff levels were set at 180 pmol/L for vitamin B12 and at 13 nmol/L for folic acid. Subjects completed two episodic recall tasks (objects and words) and two episodic recognition tasks (faces and words). RESULTS: Neither vitamin affected recognition or primary memory. Most interesting, although B12 was unrelated to recall performance, subjects with low folic acid levels showed impairment in both word recall and object recall. CONCLUSIONS: These results replicate and extend previous findings that folic acid may be more critical than B12 to memory functioning in late life. The selective effects of folic acid on episodic recall were discussed in terms of encoding and retrieval mechanisms, as well as in relation to brain protein synthesis.

Aged↗

Sirolimus (rapamycin)-based therapy in human renal transplantation: similar efficacy and different toxicity compared with cyclosporine. Sirolimus European Renal Transplant Study Group.

BACKGROUND: Sirolimus (rapamycin) is a potent immunosuppressant with a mechanism of action different from cyclosporine (CsA) or tacrolimus. METHODS: In 11 European centers, first cadaveric renal allograft recipients were randomized to CsA (n=42) or sirolimus (n=41). Dosing of these agents was concentration-controlled and open-labeled. All patients received corticosteroids and azathioprine. RESULTS: At 12 months, graft survival (98% sirolimus vs. 90% CsA), patient survival (100% vs. 98%), and incidence of biopsy-confirmed acute rejection (41% vs. 38%) were similar. Serum creatinine was lower with sirolimus, significantly (P< or =0.05) so at 3 and 4 months, and serum uric acid and magnesium were normal. Laboratory abnormalities reported significantly more often with sirolimus included hypertriglyceridemia (51% vs. 12%), hypercholesterolemia (44% vs. 14%), thrombocytopenia (37% vs. 0%), leukopenia (39% vs. 14%), and, of lesser importance, increased liver enzymes and hypokalemia. These abnormalities improved 2 months after transplantation when the sirolimus target trough level was lowered from 30 to 15 ng/ml. Occurrence of cytomegalovirus was comparable (14% vs. 12%); incidences of herpes simplex (24% vs. 10%, P=0.08) and pneumonia (17% vs. 2%, P=0.03) were higher with sirolimus. No gingival hyperplasia was seen with sirolimus, tremor was rare, and hypertension was less frequent (17% vs. 33%). Two malignancies were observed with CsA and none with sirolimus. CONCLUSIONS: Results at 12 months suggest that sirolimus can be used as base therapy in the prophylaxis of acute renal transplant rejection, and has a safety profile that differs from CsA.

Adult↗

A randomized multicenter trial of the anti-ICAM-1 monoclonal antibody (enlimomab) for the prevention of acute rejection and delayed onset of graft function in cadaveric renal transplantation: a report of the European Anti-ICAM-1 Renal Transplant Study Group.

BACKGROUND: T-cell activation through T-cell receptor engagement requires co-stimulatory molecules and also adhesion molecules such as ICAM-1. Moreover ICAM-1 mediates leukocyte invasion from the blood into tissue during inflammatory processes. In animal studies using mouse monoclonal antibodies against ICAM-1 (enlimomab), renal allograft survival has been improved and reperfusion damage from ischemia reduced. The European Anti-ICAM-1 Renal Transplant Study (EARTS) was a randomized, double-blind, parallel-group, placebo-controlled study lastingl year and performed in 10 transplant centers in Europe. METHODS: A total of 262 recipients of cadaveric kidneys were given either enlimomab or a placebo for 6 days and were given triple immunosuppressive therapy of cyclosporine, azathioprine, and prednisolone. The primary efficacy endpoint was the incidence of the first acute rejection within 3 months, and each event was assessed by a committee including investigators and independent pathologists. RESULTS: There was no significant difference in the incidences of first acute rejection at 3 months between the placebo and enlimomab groups (39% vs. 45%), and enlimomab did not reduce the risk of delayed onset of graft function (DGF) (26% vs. 31%). Neither was there a difference in patient survival (95% vs. 91%) or graft survival (89% vs. 84%) at 1 year. Fatal events occurred in 19 (7%) patients (7 placebo, 12 enlimomab). Clinically, the most important non-fatal adverse events were infections; however, there was no statistically significant difference between the incidences in the two groups (70% vs. 79%). CONCLUSION: Short term enlimomab induction therapy after renal transplantation did not reduce the rate of acute rejection or DGF.

Acute Disease↗