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Our aims were to assess the impact on health-related quality of life (HRQOL) of a controlled ileal release (CIR) formulation of budesonide in active Crohn's disease (CD) and further define the role of HRQOL, using the Inflammatory Bowel Disease Questionnaire (IBDQ), in assessing outcome in CD. A randomized trial was conducted in 258 patients with active ileal or ileocecal CD. Budesonide CIR 1.5 mg, 4.5 mg, 7.5 mg, or placebo was given b.i.d. for 8 weeks. IBDQ score changes were compared among groups. Correlations for IBDQ and Crohn's Disease Activity Index (CDAI) scores were calculated. Mean IBDQ scores improved significantly over placebo by 2 weeks in budesonide 15 mg (155+/-38; p = 0.006) and 9 mg groups (157+/-33; p = 0.0002). Bowel, systemic, social, and emotional subscores were also significantly better (p < 0.002) at 2 and 8 weeks in the 9 mg group. Improved HRQOL scores correlated well with decreased CDAI (-0.8 < r < -0.4). Average per item change in IBDQ at remission was 1.17 to 1.48. Prior surgery (p < 0.005) or current smoker (p < 0.05) status predicted poorer initial HRQOL but not response. Budesonide CIR 9 or 15 mg/day rapidly and significantly improved HRQOL in active CD.

Episodic memory for simple commands is better following enacted than verbal encoding. This has been proposed to be due to the possibility to base retrieval on motor information. Here we used PET to test the hypothesis that motor brain areas show increased retrieval-related activity following enacted compared to verbal encoding. Brain activity was also monitored during retrieval after imaginary enactment during encoding. It was found that activity in the right motor cortex was maximal following encoding enactment, intermediate following imaginary encoding enactment, and lowest following verbal encoding. These findings provide support that one basis for the facilitating effect on memory performance of overt, and to a lesser degree covert, encoding enactment is the possibility to base retrieval on motor information.

1. Joint pain is a frequent manifestation of Crohn's disease. Budesonide controlled ileal release (CIR) is a predominantly topically acting glucocorticosteroid, which is effective in treating active ileal or ileocaecal Crohn's disease. 2. Therefore, it was of interest to study the effect of this predominantly topically acting therapy on the treatment of an extraintestinal symptom of Crohn's disease by analysing data collected from budesonide CIR (Entocort; Astra Draco AB, Lund, Sweden) trials. 3. Three large studies of budesonide CIR treatment in active Crohn's disease provided a reliable source of clinical data. Of the 611 patients treated in the prospective double-blind controlled trials, 291 had joint pain (arthritis/arthralgia) at entry, which was recorded as part of the Crohn's Disease Activity Index. Statistical analysis was based on all patients treated, provided that the patient had joint pain at the start of treatment. 4. Daily oral budesonide CIR (9mg) resulted in clinical remission of joint pain in 74% (95% confidence intervals (CI) 67-82%) of patients. This outcome was nearly twice as good as placebo (41%; 95% CI 34-57%) and as good as the outcome effected by daily oral prednisolone (40mg; 72%; 95% CI 60-84%). The favourable response to budesonide CIR (9 mg) did not correlate with glucocorticosteroid-associated side effects or with adrenal suppression, which were half those in the prednisolone (40 mg/day) group. 5. The favourable outcome may relate to restitution of normal intestinal immune function.

Background & Aims: Prevention of postoperative recurrence after resection for Crohn's disease (CD) would be of great clinical benefit. The efficacy of oral budesonide for prevention of endoscopic recurrence was evaluated in patients undergoing resection for ileal or ileocecal CD., Methods: Sixty-three patients received budesonide and 66 received placebo in a double-blind, randomized trial with parallel groups. Ileocolonoscopy, including biopsy, was performed after 3 and 12 months. Indications for surgery were fibrostenosis (78 patients), disease activity (41), and other reasons (10)., Results: The frequency of endoscopic recurrence did not differ between the groups at 3 and 12 months. In patients with disease activity as indication for surgery, the endoscopic recurrence rate at the anastomosis was lower in the budesonide group at 3 months, although not significantly (21% vs. 47%; P = 0.11), and at 12 months (32% vs. 65%; P = 0.047). There was no such difference with respect to fibrostenosis as indication for surgery. No differences in adverse event patterns were found between the two groups., Conclusions: Oral budesonide, 6 mg daily, offered no benefit in prevention of endoscopic recurrence after surgery for ileal/ileocecal fibrostenotic CD but decreased the recurrence rate in patients who had undergone surgery for disease activity.

A patient approaching the final stage of his renal disease is faced with many difficult questions. Should he opt for a transplant or start on dialysis? In the case of dialysis, can he manage his treatment at home or will he need to be cared for in a clinic? Should be choose peritoneal dialysis or haemodialysis? Is the freedom of being independent from a machine, given by CAPD, as valuable as the freedom of having days without treatment, given by HD? The issues are complex and do not have a given answer. To make the proper decisions about his treatment the patient needs extensive information and support from the caregivers. Likewise, the caregivers need to know the patient well in order to give appropriate advice. In this exchange of information, the renal nurse has a very important role. Some patients may need to be dialysed in a hospital but most can get an equally good or even better dialysis treatment in a less stressful environment. A high degree of self-care is preferred by people who value independence and freedom of movement. Self-care also improves the self-confidence and increases the chances of maintaining employment and a rich social life. Self-care could mean both PD and HD, sometimes with the assistance of a spouse or a nurse. But a certain degree of self-care can also be maintained in limited-care centres and satellites, where the presence of nursing staff gives the feeling of security. For everybody involved, not least the purchasers of health care, it is desirable to keep the patients out of the costly hospital environment for as long as possible.

Background & Aims: Budesonide is a highly potent topical glucocorticosteroid that is characterized by low systemic availability as a result of high first-pass hepatic metabolism. The aim of this study was to evaluate the efficacy and safety of three doses of an enema preparation of budesonide in patients with active distal ulcerative colitis/proctitis., Methods: In a double-blind multicenter trial, 233 patients were randomized to receive either a placebo enema or budesonide enema at a dose of 0.5 mg/100 mL, 2.0 mg/100 mL, or 8.0 mg/100 mL. The primary efficacy variables were an improvement of sigmoidoscopic inflammation grade, total histopathology score, and remission rates. Effects on cortisol concentrations were also assessed., Results: After 6 weeks of treatment, there was significant improvement in sigmoidoscopy and histopathology scores in the budesonide 2.0-mg and 8.0-mg dose groups compared with placebo. Remission was achieved in 19% of patients in the 2.0-mg budesonide group (P

In three experiments, we studied memory for action events with respect to exceptions from the Tulving-Wiseman function demonstrated in experiments on recognition failure of recallable words. In Experiment 1, we examined exceptions of poor integration in a regular recognition failure condition (i.e., recognition of targets without contextual cues, followed by recall of targets in the presence of contextual cues). In Experiment 2, we examined exceptions of cue overlap in which subjects also had access to the information of contextual cues at recognition test. In Experiment 3, we attempted to equate the levels of recognition across the action and verbal encoding. In addition, the cue overlap and no-cue overlap conditions were studied in a within-subjects design. Results from the three experiments indicated that encoding enactment (episodic integration) and conceptual integration (semantic integration) are related to each other. As a consequence of this relationship, there is a larger independence between recognition and recall of well-integrated items with encoding enactment. On the other hand, for the poorly integrated items without encoding enactment, there is a larger dependence between recognition and recall. Even in the cue overlap condition, where there is a case of large dependence between recognition and recall, the same pattern of data was observed. The results are discussed in terms of an episodic integration view of encoding enactment.

The Temperament and Character Inventory (TCI) is a self-report personality questionnaire based on Cloninger's psychobiological model of personality, which accounts for both normal and abnormal variation in the two major components of personality, temperament and character. Normative data for the Swedish TCI based on a representative Swedish sample of 1,300 adults are presented, and the psychometric properties of the questionnaire are discussed. The structure of the Swedish version replicates the American version well for the means, distribution of scores, and relationships within the between scales and subscales. Further, the Swedish inventory had a reliable factor structure and test-retest performance. The results of this study confirm the theory of temperament and character as a seven-factor model of personality.

Objective: To describe the type and frequency of drug-related problems discussed in regular team meetings conducted in 15 Swedish nursing homes and report physician and staff assessments of these interventions and residents' outcomes., Data Sources and Methods: The data were collected within the context of a controlled trial with the primary aim of exploring the effects of regular team interventions on drug prescribing practices in Swedish nursing homes. In 15 experimental nursing homes, the residents' drug therapy was discussed regularly by a team consisting of a pharmacist, a physician, nurses, undernurses (similar to licensed practical nurses), and nurse's aides. The pharmacist documented problems, made changes, and observed outcomes. Following the intervention period, a questionnaire was sent to the medical staff that contained items regarding perceived outcomes, the intervention's impact on knowledge of drug therapy in the elderly, and attitudes toward the pharmacist's role., Results: Unclear indication and problematic choice of drugs were the most common drug-related problems discussed. In 19% of the situations, therapy changes were reported to have had a beneficial effect on the residents' clinical status; in 47% of the situations, staff reported no observable outcome from changes, suggesting that the changes had been appropriate. Finally, medical staff claimed in the follow-up survey that their knowledge about drug therapy had increased; they expressed an overall positive attitude toward this interactive collaboration., Conclusions: Regular intervention conducted by a multidisciplinary team incorporating a pharmacist can effectively improve prescribing practices, increase staff knowledge about appropriate drug therapy in the elderly, and result in improved quality of care for nursing home residents.

Objective: To evaluate the impact of regular multidisciplinary team interventions on the quantity and quality of psychotropic drug prescribing in Swedish nursing homes., Design: A randomized controlled trial., Setting: A sample of 33 nursing homes: 15 experimental homes and 18 control homes representing 5% of all Swedish nursing homes., Participants: The sample consisted of 1854 long-term care residents with an average age of 83 years. Seventy percent of the residents were women, and 42% had a documented diagnosis of dementia. An additional 5% had a psychotic disorder, and 7% had a diagnosis of depression., Intervention: Experimental homes participated in an outreach program that was designed to influence drug use through improved teamwork among physicians, pharmacists, nurses, and nurses' assistants. Multidisciplinary team meetings were held on a regular basis throughout the 12-month study period., Measurements: Lists of each resident's prescriptions were collected 1 month before and 1 month after the 12-month intervention. Measures included the proportion of residents with any psychotropic drug, polymedicine, and therapeutic duplication and proportion of residents with nonrecommended and acceptable drugs in each psychotropic drug class, as defined by current Swedish guidelines., Results: Baseline results show extensive psychotropic drug prescribing, with the most commonly prescribed drugs being hypnotics (40%), anxiolytics (40%), and antipsychotics (38%). After 12 months of team meetings in the experimental homes, there was a significant decrease in the prescribing of psychotics (-19%), benzodiazepine hypnotics (-37%), and antidepressants (-59%). Orders for more acceptable antidepressants also increased in the experimental homes. In the control homes there was increased use of acceptable antidepressants, but there were no significant reductions in other drug classes., Conclusions: There is excessive prescription of psychotropic drugs in Swedish nursing homes. Improved teamwork among caregivers can improve prescribing as defined by clinical guidelines.

The relationship between gender and memory has been largely neglected by research, despite occasional studies reporting gender differences in episodic memory performance. The present study examined potential gender differences in episodic memory, semantic memory, primary memory, and priming. Five hundred thirty women and 470 men, randomly sampled from the city of Umeå, Sweden, 35-80 years of age, participated in the study. There were no differences between men and women with regard to age or education, or on a measure of global intellectual functioning. As has been demonstrated previously, men out performed women on a visuospatial task and women outperformed men on tests of verbal fluency. In addition, the results demonstrated that women consistently performed at a higher level than did men on the episodic memory tasks, although there were no differences between men and women on the tasks assessing semantic memory, primary memory, or priming. The women's higher level of performance on the episodic memory tasks could not be fully explained by their higher verbal ability.

This study examined the effects of dual task requirements on age differences in free recall performance. One thousand adults ranging in age between 35 and 80 years performed a word recall task alone and concurrently with a card-sorting task (at encoding, retrieval, or both). Age differences in memory performance were substantial under single task conditions, but after correcting memory performance under dual task conditions for differences in single task performance, age did not predict performance. These results do not support the hypothesis that reduced attentional capacity in old age is underlying age differences in episodic memory.

Two important objectives in the neuroscience of memory are (1) identification of neural pathways involved in memory processes; and (2) characterization of the pattern of interactions between these pathways. Functional neuroimaging can contribute to both of these goals. Using image subtraction analysis of regional cerebral blood flow data measured with positron emission tomography, we identified brain regions that changed activity during episodic memory retrieval (visual work recognition). Relative to a baseline reading task, decreased activity was observed in bilateral prefrontal, bilateral anterior and posterior temporal, and posterior cingulate cortices. Brain regions showing increased activity were the right prefrontal (different from deactivated regions), left anterior cingulate, and left occipital cortices, and vermis of cerebellum. We then performed a network analysis with structural equation modeling to test the hypothesis that regional decreases came about through active inhibition by regions showing increased activity during retrieval. This analysis demonstrated that the influence of activated regions on deactivated regions was more negative during retrieval than during reading, confirming the inhibition hypothesis. Such confirmation could not have been made from the subtraction analysis alone because decreases can come about, at the very least, through reduction of functional influences as well as by active inhibition. The concepts of ensemble excitation and inhibition, as defined through network analysis, are introduced. We argue that is is critical to examine the combined pattern of excitatory and inhibitory influences to fully appreciate the neural basis of episodic memory.

The effect of mild aphasia (n = 9), as a result of subarachnoid haemorrhage (SAH), was evaluated against one matched (sex, age, and education) control group suffering from SAH of unknown origin without aphasia, and against one matched healthy control group. According to aphasia testing (Reinvang & Engvik, 1980), criteria for a classical diagnosis were not met. Therefore, the patients were characterized as mild aphasics: They generally displayed intact audo-verbal comprehension and repetition abilities, and they demonstrated a fluent, spontaneous speech. However, they showed phonemic and semantic paraphasias, with self-corrections; a few patients displayed alexia and agraphia. Memory performance of these three groups was evaluated by a neuropsychological test battery, designed to tap various components of verbal memory function. From the results it was concluded that: (a) Short-term memory is impaired, as regards the phonological loop and the central executive in working memory, whereas maintenance rehearsal is unaffected, given that the demands on phonological coding is minimized, (b) long-term memory is also generally impaired, whereas long-term learning and forgetting by means of subject-performed tasks proceeds within a normal range. Impairments were hypothesized to reflect less efficient central executive functions of working memory, involving generation of less appropriate semantic codes and phonological representations, (c) mildly aphasic patients are not subjectively aware of their own memory deficits, and (d) aphasia classification by means of standard procedures do not sufficiently characterize the nature of a mildy aphasic patient's memory problems.

Background & Aims: Budesonide is a corticosteroid with high topical anti-inflammatory activity and low systemic activity due to rapid hepatic metabolism. The efficacy and safety of an oral controlled-release preparation of budesonide for maintenance of remission was evaluated in patients with ileal or ileocecal Crohn's disease., Methods: In a double-blind, multicenter trial, 105 patients were randomly assigned to receive placebo or budesonide at doses of 3 or 6 mg daily for 1 year. The primary outcome measure was relapse defined by a Crohn's Disease Activity Index score of > 150 and a minimum increase of 60 points., Results: Patients receiving 6 mg of budesonide had a median time to relapse or discontinuation of therapy of 178 days compared with 124 days in those receiving 3 mg of budesonide and 39 days in those receiving placebo. However, at 1 year, the rate of relapse in the group receiving 6 mg of budesonide was similar to the rates in the 3-mg and placebo groups. Basal plasma cortisol levels and incidence of corticosteroid-associated effects were similar in the three groups., Conclusions: Oral controlled-release budesonide (6 mg/day) was well tolerated and prolonged remission in Crohn's disease of the ileum and proximal colon, but this effect was not sustained at 1-year follow-up.

Positron emission tomography (PET) was used to identify brain regions associated with two component processes of episodic retrieval; those related to thinking back in subjective time (retrieval mode) and those related to actual recovery of stored information (ecphory). Healthy young subjects recognized words that had been encoded with respect to meaning or the speaker's voice. Regardless of how the information had been encoded, recognition was associated with increased activation in regions in right prefrontal cortex, left anterior cingulate, and cerebellum. These activations reflect retrieval mode. Recognition following meaning encoding was specifically associated with increased activation in left temporal cortex, and recognition following voice encoding involved regions in right orbital frontal and parahippocampal cortex. These activations reflect ecphory of differentially encoded information.

One experiment compared the effect of elaboration on enacted and non-enacted events. The commands were either presented in a basic form (e.g., "wave your hands") or in an enriched form. The commands were enriched by adding statements to the commands of how to perform the actions (e.g., "wave your hands as a conductor"). Free- and cued-recall data showed elaboration to have a dissociative effect on enacted and non-enacted events. Memory for the non-enacted events benefited from enrichment, whereas simple enacted events were remembered to a higher extent than complex enacted events. Lack of benefit from elaboration on memory of enacted events is suggested to be due to enactment leading to a sufficient degree of item-specific processing, and a negative effect of elaboration is suggested to occur when the way of manipulating item complexity decreases the familiarity of the actions. Familiarity ratings of the items by two independent groups of subjects supported this interpretation.

When subjects study a list of B items paired with A items and are tested for recognition of the B items alone, and then for recall of the B items given the A items as cues, B items that can be recalled frequently go unrecognised. The extent of this recognition failure is predictable from a function discovered by Tulving and Wiseman (1975), which relates the probability of recognising the recallable items to the probability of recognising all items. Two kinds of exceptions to this function have been discovered: encoding exceptions and retrieval exceptions. Very few observations of retrieval exceptions exist. Four experiments described in this article provide further evidence that such exceptions occur when the B items are categorised and the A items are the names of the categories. According to a contextual account of the function and exceptions to it, these retrieval exceptions occur because the information provided by the A-item cues can be largely retrieved from the B items in the recognition test; hence, as cues, the A items do not provide much different contextual information to that provided by the B items. By this account, the function is an empirical law; exceptions fall outside the range of this law and define its boundary conditions.

Enactment during the encoding of simple imperatives has been found to improve substantially performance on conceptually driven explicit-memory tests. In two experiments the effect of this manipulation on a conceptually driven implicit test (category association) was studied. A conceptually driven explicit test (free recall) was also included. In Experiment one three different study conditions (enactment with real objects, reading, and generation) were considered. In Experiment two there were two study conditions (enactment with imaginary objects and reading). Compared to reading, generation was found to improve the performance on both free recall and category association, whereas enactment affected free recall only. In a final experiment subjects imagined that they performed the tasks, and this manipulation was found to improve the memory performance on both tests. Taken together, this pattern of results is interpreted as suggesting that free recall and category association have a process in common that is sensitive to semantic processing at study (promoted by generation and imagery, but not by enactment), and that free recall involves a retrieval process in addition that is facilitated by a rich encoding environment (provided by enactment).

The effect of retrieval enactment on memory for nouns (objects) or verbal phrases describing simple actions (e.g., "lift the box") was addressed in two experiments. In Experiment 1, the type of object involved in the actions was manipulated, with three different types of object being used (body parts, laboratory-related objects, and external objects). In Experiment 2, the integration between the verb-noun pairs was manipulated (well-integrated vs. poorly integrated). Results from both experiments showed that whereas encoding enactment (motor encoding and verbal test) substantially improved the memory performance compared with a verbal condition (verbal encoding and verbal test), retrieval enactment (verbal encoding and motor test) had no major impact on the number of recalled nouns or phrases. Moreover, there was no additional effect of dual enactment (motor encoding and motor test). The overall pattern of the results suggests that there is a fundamental difference between motor processing at encoding and motor processing at retrieval, and the lack of encoding specificity advantage for the motor modality contradicts the view that encoding enactment of verbal commands results in storage of motor representations.

Background: Corticosteroids are the most efficacious drugs for inducing remission in active Crohn's disease, but their benefits are frequently offset by serious side effects. Budesonide is a corticosteroid with high topical antiinflammatory activity but low systemic activity because of extensive hepatic metabolism. We investigated the efficacy and safety of an oral controlled-ileal-release preparation of budesonide in patients with active Crohn's disease involving the ileum or ileum and proximal colon., Methods: In a double-blind, multicenter trial, 258 patients were randomly assigned to receive placebo or one of three doses of budesonide--3, 9, or 15 mg daily. The primary outcome measure was clinical remission, as defined by a score of 150 or less on the Crohn's disease activity index., Results: After eight weeks of treatment, remission occurred in 51 percent of the patients in the group receiving 9 mg of budesonide (95 percent confidence interval, 39 to 63 percent), 43 percent of those receiving 15 mg (95 percent confidence interval, 31 to 55 percent), and 33 percent of those receiving 3 mg (95 percent confidence interval, 21 to 44 percent), as compared with 20 percent of those receiving placebo (P < 0.001, P = 0.009, and P = 0.13, respectively). Improvements in the quality of life, as measured by the patients' responses to the inflammatory bowel disease questionnaire, paralleled these remission rates. Location of disease, prior surgical resection, and previous use of corticosteroids did not affect the outcome. A total of 119 patients (46 percent) were withdrawn from the study before the trial ended, 96 because of insufficient therapeutic effects, 13 because of adverse reactions, and 10 because of noncompliance. Budesonide caused a dose-related reduction in basal and corticotropin-stimulated plasma cortisol concentrations but was not associated with clinically important corticosteroid-related symptoms or other toxic effects., Conclusions: In an eight-week trial, an oral controlled-release preparation of budesonide at an optimal daily dose of 9 mg was well tolerated and effective against active Crohn's disease of the ileum and proximal colon.

If a recognition test is followed by a cued recall test then the probability of recognition given recall generally follows the Tulving-Wiseman function. Despite this regularity two types of exceptions have been discovered. Both poor integration and cue overlap causes an observed value of recognition given recall that is higher than predicted. The present study explores the first type of exception by proposing and testing an analytical tool, which emanates from confidence ratings given to recall responses, for relating poor integration directly to variations in the degree of deviation from the function. It is demonstrated that very poor integration produces a deviation above the function, whereas a very good integration produces a deviation below the function. The effect of integration (and cue overlap) is explained by means of a conceptualization cue dependency. Support is also given to the notion that an enhanced variability of goodness of encoding contributes to an enhanced dependence between recall and recognition.

Two experiments addressed the influence of secondary task performance at encoding on recall of different features of subject-performed tasks (SPTs) involving objects (e.g., turn the wallet). In Experiment 1, memory for verbs and colors of objects was assessed, with object names serving as cues. In Experiment 2, object and color memory were assessed, with verbs serving as cues. Results from both experiments indicated a greater deterioration of memory performance under divided attention for verbal features than for colors. In addition, intention to remember did not affect performance for any feature in either experiment. The overall pattern of outcome is discussed relative to the view that encoding of verbal features of SPTs is more attention-demanding than encoding of physical task features, such as color.

Hintzman (1991; 1992) has claimed that the reason data points approximate the recognition failure function discovered by Tulving and Wiseman (1975) is that they are mathematically constrained to do so, and the reason that a few data points do not approximate the function, but are exceptions to it, is that these data points are less subject to mathematical constraints. He has additionally argued that such exceptions are more likely with low levels of recall and strong underlying sources of positive covariance. We provide empirical evidence relevant to this mathematical model using 301 observations from a database of all relevant experimental conditions published between 1973 and 1992 (Nilsson & Gardiner, 1993). We conclude that mathematical constraints have only a minor influence on the function, not the causal role assigned to them in Hintzman's (1992) model. By our account, both the function and exceptions to it reflect a single psychological principle, the functional effectiveness of contextual cues.

This paper presents a database of all published studies based on the recognition failure paradigm, which involves the study of pairs of items followed by a recognition test of the second item of each pair and a recall test of the same target item with the first item of each pair provided as a context cue. The paper also identifies, on the basis of a quantitative analysis, exceptions to the recognition failure function encompassing most data in the database. The database includes reference information about each study and a short description of materials and the manipulations made in each of the 302 experimental conditions reported. The database also includes information about the total number of observations for each condition, the overall hit rate in free or forced choice recognition, the overall probability of recall, the observed probability of recognition given recall, the predicted probability of recognition given recall, the difference between observed and predicted values, and the critical ratio between these difference scores and their overall standard deviation.

Two experiments were designed to test a claim made by Gardiner (1988) that there are generation effects in implicit memory as measured by word-fragment completion. Subjects either read words at study or generated the words from fragments. As in previous research, fragments were completed to a greater extent if they were identical at study and test than if they differed. In Experiment 1 it was found that subjects could recognize explicitly the exact form of fragments that had been used for self-generation and distinguish these from other forms of fragments. An analysis of the contingency relations between recognition of fragments and fragment completion showed a high degree of dependence between the two tests. In Experiment 2 it was found that the match of surface features between study and test was a necessary, but not sufficient, condition to produce enhancement of priming. The results are interpreted as supporting the claim that generation does involve a data-driven component in addition to semantic elaboration.

The ability of patients with Alzheimer's disease (AD) to utilize semantic category cues in order to improve memory performance was examined. Categorizable lists of words or objects were presented under five different encoding conditions: (a) nouns, (b) objects, (c) objects with a semantic orienting question, (d) objects with self-generated motoric acts, and (e) objects with experimenter-instructed motoric acts. Subjects were asked to memorize the items for a free recall test, and were subsequently provided with the category names in a cued recall test. Mildly, moderately, and severely demented AD patients, and a group of normal older adults participated in the study. Results showed that normal older adults and mildly demented AD subjects were able to utilize cues to improve memory performance in all conditions. Moderately demented patients utilized cues in all conditions except in the verbal condition (condition [a]), whereas severely demented patients utilized cues only in the motoric condition (condition [e]). These results suggest that the ability to utilize category cues following a motoric encoding is preserved later in AD than the ability to utilize cues after a semantic encoding.

In a coordinated, double-blind multi-centre trial, adults with symptoms of acute pyelonephritis were randomly assigned to receive a two-week course of oral treatment with either 400 mg norfloxacin twice daily or 1 g cefadroxil twice daily. Of 197 patients enrolled in the study, 140 could be evaluated for drug efficacy and 193 for drug safety. Norfloxacin gave a significantly higher bacteriological cure rate than cefadroxil, both at 3 to 10 days (98% versus 65%; p less than 0.0001; 95% confidence interval (CI) for difference in proportions 21-46%) and up to eight weeks (87% versus 48%; p less than 0.0001; 95% CI 25-54%) after cessation of treatment. The differences between the two regimens were most pronounced in men and in patients with complicating factors such as diabetes mellitus and urinary tract abnormalities. The clinical response during treatment did not differ between the two groups, but symptomatic recurrences at follow-up were more common in the cefadroxil group (28% versus 3%; p less than 0.0001; 95% CI 14-36%). Adverse events were more often reported by patients receiving cefadroxil (39% versus 22%; p = 0.011; 95% CI 4-30%) and consisted mainly of gastrointestinal disturbances and vulvo-vaginitis. In terms of bacteriological and clinical efficacy and safety, a two-week course of norfloxacin was superior to a two-week course of cefadroxil for oral treatment of community-acquired acute pyelonephritis.

One might argue that the decrease in the number of brain cells as a function of age could be the source of the functional age deficits in memory performance. However, this possibility seems less likely since the actual loss of neurons up to advanced age is relatively small. There are no good estimates of the loss of synapses. Golgi staining of cortical neurons would indicate that there is a loss with higher age. So far, however, the most convincing data of marked loss with age appear at the biochemical level. Most human data fail to demonstrate a decrease in cholinergic and serotonergic activity as a function of normal aging, although there is a loss of corresponding receptors. In AD/SDAT, however, there is a marked damage to these systems. Conceivably, acetylcholine may be providing informational rather than tone setting or balancing influence on memory function. This may explain the failure of cholinomimetic drugs to improve memory in AD/SDAT due to their inability to supply the informational properties of normal neuronal transmission. The catecholamines, noradrenaline and dopamine are both lost in normal aging and to a much higher degree in AD/SDAT. Animal data show that noradrenaline deficiency results in scattered attention. Such a pattern might also exist in the intact aged and through guidance by means of instructions, contextual cues, and a richer TBR information, the elderly are being forced to attend. This may promote and supersede the normal functions of the noradrenaline system by directions from external rather than internal influences, conceivably by potentiating the remaining noradrenaline neurons. The cortical motor areas are relatively spared from neuro-degenerative changes in normal aging and in AD/SDAT and this might provide a neuroanatomical basis for the elderly's and mildly to moderately demented patients' success in memory performance when motor action is involved. The role of dopamine in motor function and its stability with age in hippocampus may also provide a neurochemical basis for the preservation of memory when the subjects are allowed to act physically during encoding.

Intraperitoneal 5-fluorouracil (5-FU) was given to eight patients with unresectable colorectal liver cancer and to one patient after radical hepatectomy. A subcutaneous intraperitoneal access device was implanted, and treatment consisted of continuous infusion of 1,000 mg 5-FU/d for 5 days, repeated every 6 weeks. Evaluation of treatment was performed after every two cycles of therapy. A total of 32 infusion cycles were given. The mean steady-state concentration of 5-FU was 0.56 +/- 0.04 mumol/l (mean +/- SEM), and the total body clearance was 10.0 +/- 0.71/min mean +/- SEM). The levels of 5-FU in peripheral venous blood were stable and reproducible. When incubated in whole blood at 37 degrees C the concentration of 5-FU fell rapidly and after 2 h, only 22% of the starting level remained. When kept ice-cold, 5-FU samples were stable. Patient acceptance was excellent, and the therapy was free from complications except for slight abdominal discomfort, not enough to require alleviation by analgesic drugs. Computerized tomography (CT) scan showed stationary tumor volume after two cycles of therapy in four of eight patients who could be evaluated. It is concluded that continuous intraperitoneal infusion of 5-FU produces stable and reproducible levels of the drug in peripheral venous blood, that 5-FU is degraded by blood cells at 37 degrees C, that the use of a subcutaneous access device makes the delivery easy and safe, and that the efficacy of the therapy seems to be similar to that obtained with hepatic arterial infusion.

Free recall performance of young and old adults was examined in three memory tasks: acts carried out by the subjects (subject-performed tasks or SPTs), sentences with imagery instructions, and sentences. The subjects were presented with the same verbal information in all three tasks. No age differences were observed on free recall of SPTs, whereas typical aging effects were obtained on free recall of the other tasks. This way the data from a previous study of no age effects on SPT recall were replicated. A hypothesis about imagery as a critical factor for the lack of age differences on SPT recall gained no support. Two main concepts were proposed to account for the data: Compensation among the elderly by means of the multimodal and rich properties of SPTs, and a superior ability for a spontaneous recoding of verbal information among young adults. The results were also discussed in relation to a presumption of memory tasks as varying in attentional demands.

In a complete crossover study, balanced for sex and treatment order, we have investigated the pharmacokinetics of diltiazem in 10 healthy middle-aged volunteers. The treatments were 60 mg t.i.d. and 120 mg t.i.d. during 14 days' treatment, with the last dose pulsed with 1.85 MBq [14C]diltiazem. The absorption was rapid and did not differ between treatments. The disposition could be appropriately described using a two-compartment model with terminal half-lives of 6.57 +/- 1.41 h (mean +/- SD) after 60 mg t.i.d. and 5.44 +/- 0.66 h after 120 mg t.i.d. The half-life of the metabolite N-demethyldiltiazem (MA) was similar to that of diltiazem, whereas the half-lives of deacetyldiltiazem (M1) and N-demethyldeacetyldiltiazem (M2) were longer. The plasma concentrations and areas under the curve found after doubling of the dose were not significantly different from dose-adjusted directly proportional estimations. However, the mean concentration of MA in percent of diltiazem concentration was significantly higher at the lower-dose regimen 41 +/- 11% versus 36 +/- 8%, whereas the corresponding values for M1 were 11 +/- 3% versus 11 +/- 4% and for M2 12 +/- 4% versus 12 +/- 6%, respectively. The median cumulative excretions of radioactivity during 120 h were 90 and 93%, respectively. The drug was mainly excreted in urine (73 versus 73%, median), the remaining amounts were eliminated in feces.

Three groups of patients with dementia of the Alzheimer type (mildly, moderately and severely demented) and two groups of healthy older adults (73 and 82 yr old) were examined on free and cued recall of subject-performed tasks (SPTs) or verbally presented sentences depicting the same verbal information as the SPTs. Results indicated that all groups examined performed better on SPTs than on the verbal task. In addition, for all groups cuing effects were greater in the SPT task than in the verbal task.

Patients with a ruptured supratentorial aneurysm undergoing early surgery after the subarachnoid haemorrhage were treated postoperatively with nimodipine to prevent delayed ischaemic dysfunction. It was given first as a continuous intravenous infusion 2 mg/h (mean dose 0.5 micrograms/kg/min) for at least 7 days, and then orally (45 mg X 6) for at least a further 7 days. During the i.v. infusion, the mean plasma concentration was 26.6 +/- 1.8 ng/ml. The plasma clearance ranged from 0.57 to 1.771/kg/h and was negatively correlated with the age of the patient. Immediately prior to successive oral doses, the mean plasma concentration was 13.2 ng/ml (range less than 3-38.8 ng/ml). The peak level was usually found after 1 h; it ranged from 7.0-96.0 ng/ml. Mean bioavailability was 15.9%. The nitropyridine metabolite was found in measurable concentrations only after oral treatment with nimodipine. In some cases, the concentration of metabolite exceeded that of the parent compound. The three patients investigated who developed delayed ischaemic dysfunction had plasma concentrations well within the range in patients who did not, so it seems unlikely that the therapeutic failure could be attributed to individual deviations in the pharmacokinetics of the drug.

Three experiments were discussed as a means of bridging the gap between biological and psychological data on aging and memory. Memory performances of young-old (73 year-old) and old-old (82 year-old) subjects were compared. The common denominator of these experiments was that contextual or cognitive support had been provided at study and/or test. The rationale behind discussing these experiments in the present context was that subjects should be able to use this support to focus attention on the critical aspects of the to-be-remembered information; thereby the subjects should be able to compensate for neurological degeneration pertinent to attentional difficulties. The nature of the differences between young-old and old-old subjects was found to vary among tasks. Study 1 demonstrated qualitative differences between young-old and old-old subjects, whereas Studies 2 and 3 demonstrated the differences to be merely quantitative in nature. Implications for memory training programs for the elderly were discussed.

The pharmacokinetics of diltiazem in healthy middle-aged volunteers have been investigated after single and multiple doses. Twenty men or women were recruited and were given one single dose and one steady-state treatment in a crossover fashion. Ten were given 60-mg single dose and 60-mg t.i.d. during 14 days and 10 received 120 mg as a single dose and as 120-mg t.i.d. The single dose and the last dose in steady state were pulsed with 1.85 MBq [14C]diltiazem. The absorption was rapid and did not differ between treatments. The disposition could be described using a two-compartment model with terminal half-lives of 6.27 +/- 3.23 h (mean +/- SD) after a single dose of 60 mg diltiazem, 6.05 +/- 1.59 h after 60-mg diltiazem t.i.d., 5.85 +/- 1.04 h after 120-mg diltiazem and 5.90 +/- 0.69 h after 120-mg diltiazem t.i.d. The half-life of the metabolite N-demethyldiltiazem was similar to that of diltiazem whereas the half-lives of the metabolites deacetyldiltiazem and N-demethyldeacetyldiltiazem were longer. The area under the curve of diltiazem in a dosing interval at steady state increased significantly compared with the single dose, indicating an increased bioavailability after repeated dosing, probably because of decreased presystemic elimination. The cumulative excretions of radioactivity in urine within 120 h were 72 +/- 5%, 71 +/- 8%, 71 +/- 6%, and 73 +/- 4%, respectively. The remaining amounts were excreted in feces.

In two experiments four different conditions of visual presentation were studied with the purpose of furthering our understanding of the role of temporal and spatial factors underlying modality effects in single-trial free recall. Enriching spatial factors in the visual presentation did not produce a higher performance in the recency part of the serial-position curve, and it was therefore concluded that the modality effect could not be due to any visual handicap. A lag distribution measure was suggested and applied to the data to characterize output order (the order of recall) in single-trial free recall. The two experiments carried out used a within-subjects and a between-subjects design, respectively, and illustrate the importance of the methodological difference between these two designs.

Antacids and anticholinergic drugs may delay gastric emptying and cause reduced absorption of isoniazid, but the influence of reduced gastric acidity has not been determined. In the present investigation, the influence of cimetidine and ranitidine on uptake and elimination of isoniazid was determined in six male and seven female healthy volunteers. The group comprised five rapid and eight slow acetylators, similar to the proportions in the general population. H2 blockers did not delay or reduce uptake of isoniazid, which thus seemed to be pH independent. Neither the acetylation of isoniazid nor the oxidative metabolism of acetylated isoniazid appeared to be affected by cimetidine or ranitidine.

We have investigated the pharmacokinetics of 14C-labeled diltiazem, 20 mg, given as an i.v. infusion over 20 min in 10 healthy volunteers. This disposition of the drug could be described using a two-compartment model with half-lives of 0.40 +/- 0.48 h (mean +/- SD) in the alpha phase and 2.77 +/- 0.82 h in the beta phase. Systemic clearance was 992 +/- 159 ml/min; the volume of the central compartment was 119 +/- 77 L, and the volume of distribution at steady state was 209 +/- 56 L. The concentrations of metabolites (deacetyldiltiazem, N-demethyldiltiazem, and N-demethyl-deacetyldiltiazem) were low, and no pharmacokinetic parameters for these could be calculated. The median cumulative excretion of radioactivity during 120 h was 87.3%. The drug was mainly excreted in urine (71.1 +/- 7.8%), and the remaining amounts was excreted in feces. There were slight but significant decreases in supine systolic and diastolic blood pressures and heart rate. The PQ interval was significantly prolonged for 5 h, and in multiple regression analyses there were good correlations (p less than 0.01) between PQ intervals and logarithms of plasma concentrations of diltiazem.

Young, old, alcohol intoxicated, and sleep deprived subjects studied weakly and strongly related word pairs, and were tested in lexical decision priming and cued recall. Results showed memory deficits for old, alcohol intoxicated, and sleep deprived subjects in cued recall of weakly related pairs. In contrast, there were no differences between these three groups and a control group of young subjects in cued recall of strongly related pairs, and there were no differences between groups in priming. This pattern of results is interpreted to support (a) a hypothesis of functional similarities between the memory deficits associated with adult ageing, alcohol intoxication, and sleep deprivation; (b) the notion that memory deficits in these subjects are more likely to occur in tasks which require effortful rather than automatic processes; and (c) the view that the memory deficits observed are due to inefficiencies at both encoding and retrieval.