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Biomedical subjects

L Nyberg

Publications and source records attributed to L Nyberg.

At least 19 recordsLinked to original sources
PubMed1999

The diagnosis of interstitial cystitis revisited: lessons learned from the National Institutes of Health Interstitial Cystitis Database study.

PURPOSE: The lack of a precise working definition of interstitial cystitis may have resulted in the de facto use of the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK) "research" definition by clinicians. We evaluated these strict criteria in light of the broader inclusion criteria for patients evaluated in the Interstitial Cystitis Database study to determine their utility in clinical practice as a useful basis for the diagnosis of interstitial cystitis. MATERIALS AND METHODS: A total of 379 women who completed screening for the Interstitial Cystitis Database before January 1, 1996 met the basic criteria of urinary frequency, urgency or pain for at least 6 months in duration without a diagnosable etiology. Of these patients 148 underwent cystoscopy and hydrodistention of the bladder as a part of the evaluation. All patients were followed for a minimum of 1 year. Comparisons were made between patients judged to have a clinical diagnosis of interstitial cystitis and those who met the NIDDK research definition of the syndrome. RESULTS: Almost 90% of patients potentially meeting NIDDK criteria are believed by experienced clinicians to have interstitial cystitis, confirming the research value of these criteria in defining a homogeneous population for study. However, strict application of NIDDK criteria would have misdiagnosed more than 60% of patients regarded by researchers as definitely or likely to have interstitial cystitis. CONCLUSIONS: The NIDDK criteria are too restrictive to be used by clinicians as the diagnostic definition of interstitial cystitis.

Cystitis, Interstitial↗
PubMed1998

Functional brain imaging of episodic and semantic memory with positron emission tomography.

Human memory is composed of several independent but interacting systems. These include a system for remembering general knowledge, semantic memory, and a system for recollection of personal events, episodic memory. The results of positron emission tomography (PET) studies of regional cerebral blood flow indicate that networks of distributed brain regions subserve episodic and semantic memory. Some networks seem to be generally engaged in memory processes whereas the involvement of others is specific to factors such as the type of information to be remembered or the level of retrieval success. The PET findings help to understand memory dysfunction (a) by showing that multiple brain regions are involved in different memory processes and (b) by sharpening the interpretation of the functional role of different brain regions.

Brain↗
PubMed1998

Fractures after stroke.

Fractures are a serious complication after stroke. Among patients with femoral neck fractures, a large subgroup have had a previous stroke. This study aimed to investigate the incidence of fractures after stroke. Included in the study were 1139 patients consecutively admitted for acute stroke. Fractures occurring from stroke onset until the end of the study or death were registered retrospectively. Hip fracture incidence was compared with corresponding rates from the general population. Patients were followed up for a total of 4132 patient-years (median 2.9 years). There were 154 fractures in 120 patients and median time between the onset of stroke and the first fracture was 24 months. Women had significantly more fractures than men (chi 2 = 15.6; p < 0.001). In patients with paresis most of the fractures affected the paretic side (chi 2 = 22.5; p < 0.001) and 84% of the fractures were caused by falls. Hip fracture was the most frequent fracture and the incidence was 2-4 times higher in stroke patients compared with the reference population. Fractures are thus a common complication after stroke. They are usually caused by falls and affect the paretic side. It is necessary to focus on the prevention of post-stroke fractures, including the prevention of both falls and osteoporosis.

Accidental Falls↗
PubMed1998

Mapping episodic memory.

This paper presents an analysis of brain regions generally associated with a frequently used episodic memory task; visual word recognition. The results from five positron emission tomography studies of regional cerebral blood flow, involving a total of nine pairwise comparisons of brain activity related to episodic retrieval and to performance on non-episodic reference tasks, were considered. Across studies, increased activity has been observed in the right anterior and posterior prefrontal, anterior cingulate, bilateral parietal, and cerebellar regions. Decreased activity has been found in bilateral temporal and left midfrontal regions. Comparison of this activation pattern with those of other memory tasks, episodic and semantic, indicate that the right anterior and posterior prefrontal regions guide processes selectively demanded by episodic memory retrieval. There is suggestive evidence from subtraction analyses that these prefrontal regions are activated by different processing components, and analyses of functional connectivity provide further support for functional differentiation. These analyses also point to a critical role of medial-temporal brain regions in episodic retrieval. Taken together, these results show that episodic memory retrieval is mediated by an extensive set of brain regions, some of which seem to be specifically engaged by episodic remembering.

Animals↗
PubMed1998

Human proximal duodenal alkaline secretion is mediated by Cl-/HCO3- exchange and HCO3- conductance.

The proximal duodenal epithelium secretes bicarbonate into an adherent mucus layer, thereby protecting the mucosa from injury by gastric acid and pepsin. While bicarbonate secretion is stimulated and inhibited by a number of agonists and antagonists, the apical anion transport pathways have not been addressed fully. The objective was to assess if apical Cl-/HCO3- exchange and Cl-:HCO3- conductance are involved in duodenal mucosal bicarbonate secretion (DMBS). In healthy volunteers, the proximal 4 cm of duodenum was isolated, perfused with either saline or 4,4'-diisothiocyano-2,2'-disulfonic acid (DIDS), and bicarbonate secretion and transepithelial potential difference (PD) were stimulated by either PGE2 or the phosphodiesterase inhibitor theophylline to increase cyclic AMP. Luminal DIDS abolished PGE2-stimulated DMBS, yet had no effect on the increase in PD and failed to significantly alter theophylline-induced DMBS and PD. Therefore, in human proximal duodenum, it appears that PGE2 and cAMP activate distinct HCO3- transport pathways likely involving a DIDS-sensitive Cl-/HCO3- exchanger and DIDS-insensitive HCO3- conductance.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1998

Pharmacokinetics of bambuterol in healthy subjects.

AIMS: To study the pharmacokinetics and bioavailability of the prodrug bambuterol and its bronchodilator moiety terbutaline in healthy subjects. METHODS: Eight healthy subjects (four women) received intravenous doses of bambuterol and terbutaline. On a third occasion, they, plus another four subjects, ingested oral bambuterol as a single dose followed by repeated doses once daily for 7 days. Plasma concentrations and urinary excretion of bambuterol and terbutaline were measured. RESULTS: After intravenous administration, renal clearances of bambuterol and terbutaline were similar (about 140 ml min(-1)), but there was a five-fold difference in total clearance (bambuterol 1.25 l min(-1), terbutaline 0.23 l min(-1)). Volume of distribution (Vss) was 1.6 l kg(-1) b.w. for both substances. A similar renal clearance of bambuterol was found during oral administration but that of terbutaline decreased (to about 120 ml min(-1)). Mean terminal half-life of bambuterol was 2.6 h after intravenous and 12 h after oral administration, implying that uptake was rate-limiting. Mean residence time of terbutaline generated from oral bambuterol was 34 h compared with 8.0 h when terbutaline as such was infused. Generated terbutaline had a bioavailability of 36% (28-46) after intravenous and 10.2% (6.1-13.2) after oral administration of the prodrug. Bambuterol was well tolerated. The mean activity of plasma cholinesterase, an enzyme catalyzing bambuterol metabolism, was inhibited between 30-60% during repeated oral dosing. It virtually regained original activity within 48 h after the last dose. CONCLUSIONS: The plasma concentration ofterbutaline fluctuated little during repeated oral administration (mean peak: trough ratio 1.9), as a result of prolonged absorption of bambuterol and slow formation of terbutaline. Thus, the pharmacokinetic properties of bambuterol make it suitable for oral once-daily dosage.

Administration, Oral↗
PubMed1998

Pharmacokinetics of bambuterol in subjects homozygous for the atypical gene for plasma cholinesterase.

AIMS: It has been assumed that both plasma cholinesterase (EC 3.1.1.8) and oxidative enzymes are needed for optimum formation of the bronchodilator terbutaline from its biscarbamate prodrug bambuterol. The present study aimed at investigating the fate of bambuterol in subjects with deficient plasma cholinesterase but with normal oxidative (CYP2D6) capability. METHODS: The pharmacokinetics of bambuterol and terbutaline were studied in four healthy subjects (two men and two women) being homozygous for the atypical gene for plasma cholinesterase. Their oxidative metabolism was apparently good as they were all rapid metabolizers of debrisoquine. Bambuterol hydrochloride 20 mg was given orally once daily for 10 days, and plasma and urine samples were taken for 1.5 days (plasma) and 4.5 days (urine) after administration of the last dose. RESULTS: The pharmacokinetic parameters in the present study were grossly similar to those found in a study of bambuterol in subjects with normal plasma cholinesterase activity (N). However, subjects with atypical cholinesterase had a shorter terminal half-life of bambuterol (a measure of uptake rate), 4.8-12.6 h vs 8.3-22.3 h in N, and slightly higher plasma concentrations of bambuterol (average concentrations 1.9-3.7 nmol l(-1) vs 1.5-3.1 nmol l(-1) in N). Peak/trough terbutaline plasma concentrations ratios (2.1-3.2) were somewhat increased, but average plasma concentrations (8.3-14.5 nmol l(-1)) and terminal half-life (16.5-21.8 h) of terbutaline did not differ. CONCLUSIONS: In Caucasian populations, one subject out of 2500 is homozygous for the atypical gene for plasma cholinesterase. The atypical enzyme has a much lower affinity for bambuterol than the normal enzyme. Nevertheless, the subjects with atypical cholinesterase were able to produce terbutaline as efficiently as normal subjects. This might be explained by an altered uptake and metabolism in the absence of plasma cholinesterase, or the importance of this enzyme for the formation of terbutaline from bambuterol in vivo may have been overestimated.

Adult↗
PubMed1998

Digestion of ceramide by human milk bile salt-stimulated lipase.

BACKGROUND: There is a renewed interest in metabolism of sphingolipids because of their role in signal transduction. Sphingomyelin is the dominating phospholipid in human milk but its metabolism and possible function in the gastrointestinal tract of breast fed infants is unknown. We explored whether bile salt-stimulated milk lipase has a role in sphingolipid metabolism. METHODS: In vitro assays of sphingomyelinase and ceramidase activities, using radiolabeled substrates, human milk samples and purified native and recombinant variants of bile salt-stimulated milk lipase with or without known activators or inhibitors. RESULTS: Human whey and purified lipase catalysed hydrolysis of palmitoyl-labeled ceramide with the highest rate around pH 8.5-9.0. 1 mg of lipase hydrolysed 0.7 micromol ceramide in one hour at pH 8.5 in presence of 4 mM bile salt. The activity of whey was inhibited by antibodies towards human bile salt-stimulated milk lipase, indicating that this lipase accounted for virtually all ceramidase activity in the milk. In contrast, bile salt-stimulated milk lipase showed no activity against sphingomyelin. However we give evidence of a separate, hitherto unknown, acid sphingomyelinase in human milk. Under the used in vitro conditions this sphingomyelinase could account for hydrolysis of half of milk sphingomyelin in one hour. CONCLUSIONS: Human milk bile salt-stimulated milk lipase hydrolyses ceramide and may thus have a role in sphingomyelin digestion, but only after initial hydrolysis to ceramide and phosphorylcholine. Part of the latter could be carried out in the stomach by the acid milk sphingomyelinase now described. We speculate that these two milk enzymes may be of importance for optimal use of human milk sphingolipids.

Amidohydrolases↗
PubMed1998

Attention, frailty, and falls: the effect of a manual task on basic mobility.

OBJECTIVE: To investigate the effect of a second task on balance and gait maneuvers used in everyday life. Our hypothesis was that those who were more distracted by a familiar manual task performed concurrently with functional maneuvers were more frail and more prone to falls. DESIGN: A cross-sectional design with prospective follow-up for falls. SETTING: Sheltered accommodation in Umeå, Sweden. PARTICIPANTS: Forty-two residents (30 women, 12 men; mean age +/- SD = 79.7 +/- 6.1 years), ambulant with or without a walking aid, able to follow simple instructions and able to carry a tumbler. MEASUREMENTS: Timed Up & Go (TUG), i.e., the time taken to rise from an armchair, walk 3 meters, turn round, and sit down again. TUG was repeated with an added manual task (TUGmanual), which was to carry a glass of water while walking. The Montgomery-Asberg Depression Rating Scale, Barthel Index, Functional Reach, Mini-Mental State Examination, and Line Bisection test were used to assess for frailty. The subjects were followed-up prospectively regarding falls indoors for a period of 6-months. RESULTS: Subjects with a time difference (diffTUG) between TUGmanual and TUG of > or = 4.5 seconds were considered to be distracted by the second task. Ten subjects had a difference in time of > or = 4.5 seconds. These subjects were more frail, and seven of them fell indoors during the follow-up period (odds ratio 4.7, 95%Confidence Interval (CI) 1.5-14.2). CONCLUSION: The time difference between the TUGmanual and the TUG appears to be a valid marker of frailty and a useful tool for identifying older persons prone to falling.

Accidental Falls↗
PubMed1998

In-patient rehabilitation after stroke: outcome and factors associated with improvement.

A study aimed at examining the outcome of activities of daily living (ADL) of patients undergoing geriatric stroke rehabilitation was performed. Background and admission data of 99 patients surviving the acute phase and needing further hospital rehabilitation were registered. Forty per cent of the patients improved their ADL ability. The logistic regression modelling with the dichotomous dependent variable improvement versus no improvement showed the following factors associated with improvement: a diagnosis of intracerebral haemorrhage, male sex, high postural stability score at the admission and cohabitation. In conclusion, the most severely affected stroke patients, especially patients with intracerebral haemorrhage, have a great potential for improving their ADL. The results of the logistic regression model can serve as a useful guide when it comes to identifying patients that stand a fair chance of improving during their rehabilitation stay. Equally important, patients with a poor rehabilitation prognosis who may need intensified rehabilitation efforts to achieve optimum improvement can now be identified.

Activities of Daily Living↗
PubMed1997

Age-related differences in effective neural connectivity during encoding and recall.

Age-related differences in brain activity may reflect local neural changes in the regions involved or they may reflect a more global transformation of brain function. To investigate this issue, we applied structural equation modeling to the results of a positron emission tomography (PET) study in which young and old adults encoded and recalled word pairs. In the young group there was a shift from positive interactions involving the left prefrontal cortex during encoding to positive interactions involving the right prefrontal cortex during recall, whereas in the old group frontal interactions were mixed during encoding and bilaterally positive during recall. The present results suggest that age-related changes in neural activation are partly due to age-related changes in effective connectivity in the neural network underlying the task.

Adult↗
PubMed1997

Alkaline sphingomyelinase activity is decreased in human colorectal carcinoma.

BACKGROUND: The metabolism of sphingomyelin generates important signals regulating cell proliferation and apoptosis. Previous studies found that the administration of colon carcinoma carcinogen was associated with an accumulation of membrane sphingomyelin, and that dietary sphingomyelin inhibited promotion of experimental colon carcinoma in mice, indicating that the abnormal metabolism of sphingomyelin is linked to colon carcinoma development. However, the changes in sphingomyelinase (SMase) activity in colon carcinoma have not been directly studied. The authors identified, specifically in the intestine, a distinctive alkaline SMase that differs from the known acidic and neutral SMases. The functions and clinical implications of the enzyme are unknown. This study examined the changes in all three SMase activities in human colorectal carcinoma. METHODS: Tissue samples were taken from colorectal carcinoma and normal mucosa from 18 patients. After homogenization, the activities of acidic, neutral, and alkaline SMase, as well as ceramidase and alkaline phosphatase, were determined. The enzyme activities in cancer tissue were compared with normal tissue from the same patients. RESULTS: In the normal tissue, there is an activity gradient from the ascending colon to the rectum for neutral and alkaline SMases but not for acidic SMase. In colorectal carcinoma, alkaline SMase activity was preferentially decreased by 75%, whereas acidic and neutral SMase activity decreased by 30% and 50%, respectively. No changes could be found for either ceramidase or alkaline phosphatase activity. CONCLUSIONS: Alkaline SMase activity preferentially decreases in human colorectal carcinoma, suggesting a regulatory role of the enzyme in colon mucosa cell proliferation.

Adult↗
PubMed1997

Age-related differences in neural activity during memory encoding and retrieval: a positron emission tomography study.

Positron emission tomography (PET) was used to compare regional cerebral blood flow (rCBF) in young (mean 26 years) and old (mean 70 years) subjects while they were encoding, recognizing, and recalling word pairs. A multivariate partial-least-squares (PLS) analysis of the data was used to identify age-related neural changes associated with (1) encoding versus retrieval and (2) recognition versus recall. Young subjects showed higher activation than old subjects (1) in left prefrontal and occipito-temporal regions during encoding and (2) in right prefrontal and parietal regions during retrieval. Old subjects showed relatively higher activation than young subjects in several regions, including insular regions during encoding, cuneus/precuneus regions during recognition, and left prefrontal regions during recall. Frontal activity in young subjects was left-lateralized during encoding and right-lateralized during recall [hemispheric encoding/retrieval asymmetry (HERA)], whereas old adults showed little frontal activity during encoding and a more bilateral pattern of frontal activation during retrieval. In young subjects, activation in recall was higher than that in recognition in cerebellar and cingulate regions, whereas recognition showed higher activity in right temporal and parietal regions. In old subjects, the differences in blood flow between recall and recognition were smaller in these regions, yet more pronounced in other regions. Taken together, the results indicate that advanced age is associated with neural changes in the brain systems underlying encoding, recognition, and recall. These changes take two forms: (1) age-related decreases in local regional activity, which may signal less efficient processing by the old, and (2) age-related increases in activity, which may signal functional compensation.

Adult↗
PubMed1997

Epidemiology of interstitial cystitis.

OBJECTIVES: To discuss what is currently known about the population prevalence of interstitial cystitis (IC) and demographic characteristics of IC patients. METHODS: Changes over time in the criteria for diagnosis of IC are described. The 3 published studies of the population prevalence of IC are reviewed. Epidemiologic issues important in the design of studies of IC are cited. RESULTS: IC is a disease of chronic voiding symptoms. There is very little reliable information published on the etiology, risk factors, or number of persons affected. The criteria used for diagnosis of IC by different investigators have been variable. In 1988, research criteria for a case definition of IC were published, to be applied for IC patients enrolled in National Institutes of Health-funded studies. Three published studies of the population prevalence of IC are available. Each study used different criteria for defining a case of IC, and none used the NIH research criteria to define a case. Prevalence estimates for IC vary significantly, from 10 cases/100,000 reported in Finland in 1975, (based on hospital record review), to 30/100,000 in the United States in 1987, (based on a mailed survey of board certified urologists), to 510 cases/100,000 in the United States in 1989, (based on participant self-report in the 1989 National Health Interview Survey). It is unclear the extent to which these estimates represent true differences in prevalence, rather than reflect the different methods used to define an IC case. Several investigators have reported demographic characteristics of the IC patients followed in their clinics. All studies of adults show a marked female predominance, with reported onset of symptoms generally in the middle years of life. Patients may experience a delay of years from the onset of symptoms to the time of definitive diagnosis. The natural history of symptoms of IC has been reported to be that of a subacute onset with a rapid peak in severity, and then a relatively constant plateau of chronic symptoms thereafter. However, many patients do experience remissions and flares in their disease symptoms. CONCLUSIONS: Few therapies for IC have been evaluated using rigorous epidemiologic methods. Many questions remain to be answered. New studies of IC should include epidemiologic consultation at the stage of study design.

Cystitis, Interstitial↗
PubMed1997

Brain regions differentially involved in remembering what and when: a PET study.

Recollecting a past episode involves remembering not only what happened but also when it happened. We used positron emission tomography (PET) to directly contrast the neural correlates of item and temporalorder memory. Subjects studied a list of words and were then scanned while retrieving information about what words were in the list or when they occurred within the list. Item retrieval was related to increased neural activity in medial temporal and basal forebrain regions, whereas temporal-order retrieval was associated with activations in dorsal prefrontal, cuneus/precuneus, and right posterior parietal regions. The dissociation between temporal and frontal lobe regions confirms and extends previous lesion data. The results show that temporal-order retrieval involves a network of frontal and posterior brain regions.

Adult↗
PubMed1997

Correlation between frontal lobe functions and explicit and implicit stem completion in healthy elderly.

The authors investigated the relationship between performance on neuropsychological tests, which were sensitive to medial-temporal and frontal lobe function, and implicit and explicit stem completion in a group of healthy elderly participants (mean age = 77.3 years). Several stem-completion conditions varying in the size of the search space and the specificity of the cues were included. Across conditions, performance on a frontal lobe sensitive test (word fluency) and on medial-temporal tests (California Verbal Learning Test; delayed recall) correlated with explicit stem completion. The correlations between frontal and medial-temporal test performance and implicit stem completion were weaker. However, a relationship was observed between frontal lobe functioning and stem completion when (a) the search space was large and the cues were constrained and (b) when the search space was limited and the cues were relatively unconstrained. Therefore, the role of the frontal lobes in implicit stem completion seems to be to detect bias resulting from prior study, and this involvement can only be revealed when the interaction between the size of the search space and the retrieval cues (a) makes bias detection necessary and (b) allows it to play a role. The stronger involvement of the frontal lobes in explicit stem completion likely reflects strategic retrieval processes, and the medial-temporal lobe involvement may be related to verification processes.

Aged↗
PubMed1997

The use of physical restraints in elder care in relation to fall risk.

Physical restraints are a frequently used but disputed method to prevent falls. The aim of the present study was to investigate how the use of restraints in institutional elder care relates to previous falls and to the estimated fall risk of the individual patient. A total of 1142 patients, mean age 82 years, were included in the study. A questionnaire, the Multi-Dimensional Dementia Assessment Scale (MDDAS), was used to measure motor function, vision, hearing, ADL performance, behavioral symptoms, psychiatric symptoms, cognitive impairment and use of medication. Questions concerning the use of physical restraints and known previous falls were added to the instrument. Based on data from the questionnaire (MDDAS), a score on the Downton Fall Risk Index was calculated for each patient. All in all, 248 (22%) of the patients had been subject to restraints and for 155 of them (14%) such measures had been taken to prevent falls. Only weak connections were found between the restraining of patients to prevent falls and the prevalence of known previous falls during hospital stay (phi = 0.05), and estimated fall risk (phi = 0.07). The results indicate that the use of physical restraints is poorly connected with the estimated fall risk. Therefore, this study may point to a possible overuse of these measures.

Accidental Falls↗