Component analysis of verbal fluency in patients with schizophrenia.

OBJECTIVE: Clustering and-switching components of phonemic fluency performance were compared in patients with schizophrenia and healthy normal controls. BACKGROUND: These components were selected to provide evidence for a specific anatomic locus for the breakdown of language processes or for a multiple-disease model of schizophrenia. METHOD: As part of a larger battery of neuropsychological tests, phonemic fluency tests were administered on an individual basis. On separate 60-second trials, participants were instructed to generate words beginning with the letters C, F, and L, excluding proper names and variants of the same word. Three scores were obtained for each participant: (1) number of words generated, excluding errors and repetitions; (2) mean cluster size; and (3) raw number of switches. RESULTS: The patients showed small but significant impairments in clustering and larger impairments in switching relative to normal controls. CONCLUSIONS: This pattern suggests a relatively greater deficit in functioning in the frontal lobe than in the temporal lobe. However, neither measure was able to completely discriminate patients with schizophrenia from controls. Moreover, differences in fluency performance were observed among subtypes of schizophrenia. Taken together, the findings of impaired performance for both aspects of fluency, differences between subtypes, and the failure to completely discriminate patients with schizophrenia from controls indicate that there is not a single marker of the disease, at least among these fluency variables. Instead, the current findings are more supportive of a multiple-disease model of schizophrenia.

Anterograde and retrograde memory in children anesthetized with propofol.

Prior to anesthesia with propofol for gastrointestinal endoscopy, sets of pictures were presented to 20 children and adolescents (M age = 12 years). Word pairs (e.g., "hiking-woods") were presented via earphones after the children were anesthetized. Upon regaining consciousness, the children were tested for explicit memory of both the picture sets and word pairs by free recall, cued recall, and yes/no recognition. Implicit memory was tested by free association to category cues for the pictures and by word association for the word pairs. Postoperative testing revealed retrograde memory for material presented preoperatively but total amnesia for material presented intraoperatively. There was no evidence of implicit memory for material not available explicitly. The finding of uninterrupted ability to retain and retrieve information presented prior to anesthesia despite total anterograde amnesia has implications for preoperative communication directed toward pediatric patients as well as for intraoperative communication among surgical staff.

Longitudinal analysis of phonemic clustering and switching during word-list generation in Huntington's disease.

Two characteristics of word-list generation performance are forming clusters (i.e., contiguous words from the same subcategory) and switching among them. Patients with frontal lobe pathology show reduced switching on letter-cued word generation tasks, and clustering has been associated with temporal lobe functioning. Letter-cued word generation was examined in 72 patients with Huntington's disease (HD) and 41 healthy participants of equivalent age and education. As predicted, the patients showed reduced switching but normal clustering. In addition, switching but not clustering correlated inversely with disease severity, as measured by both movement and mental status scales. Furthermore, 5-year longitudinal analysis revealed a monotonic decrease in switching over time, whereas clustering performance remained stable. Control participants performed uniformly over time on both measures. These results are consistent with a progressive reduction in cognitive flexibility attributed to disruption of frontal-subcortical circuits secondary to neostriatal pathology in HD.

The efficacy and safety of aprotinin use in cardiac surgery.

BACKGROUND: The serine protease inhibitor aprotinin has received much attention in cardiac surgical practice as a pharmacologic intervention to improve the hemostatic derangement associated with cardiopulmonary bypass. This review highlights the major studies undertaken to investigate the efficacy and safety of aprotinin use in both primary and repeat coronary artery bypass graft surgical procedures. METHODS: There have been at least 45 controlled studies in more than 7,000 patients in a variety of patient populations. These have ranged from primary coronary artery bypass graft and valve operations to complex reoperation procedures, including aortic arch reconstructions and thoracic organ transplantation. The recently completed International Multicenter Graft Patency Experience trial, the largest study to date, involved 870 patients at 13 international sites. The study examined the effects of aprotinin on graft patency, incidence of myocardial infarction, and blood loss in patients undergoing primary coronary artery bypass graft operations with cardiopulmonary bypass. RESULTS: Twenty-one studies in approximately 5,000 patients undergoing primary coronary artery bypass graft or valve operations reported 33% to 66% reduction in blood loss with full-dose aprotinin therapy; 15 of the same studies reported significant reductions in transfusion requirements, ranging from 31% to 85%. The recently completed International Multicenter Graft Patency Experience study observed a significant reduction in thoracic-drainage volume of 43% (p < 0.0001) and a 49% (p < 0.001) reduction in the requirement for allogeneic blood transfusions. Aprotinin did not affect the occurrence of definite myocardial infarction (aprotinin, 2.9% versus placebo, 3.8%) or mortality (aprotinin, 1.4% versus placebo, 1.6%). There was no observed difference in the patency of internal mammary artery bypass grafts from all study sites in aprotinin- versus placebo-treated patients (aprotinin, 98.2% versus placebo, 98.0%). CONCLUSIONS: Given the risks and costs associated with excessive bleeding and transfusions and the limited supply of banked blood, aprotinin represents an important and safe approach to blood conservation.

Analyses of coronary graft patency after aprotinin use: results from the International Multicenter Aprotinin Graft Patency Experience (IMAGE) trial.

OBJECTIVE: We examined the effects of aprotinin on graft patency, prevalence of myocardial infarction, and blood loss in patients undergoing primary coronary surgery with cardiopulmonary bypass. METHODS: Patients from 13 international sites were randomized to receive intraoperative aprotinin (n = 436) or placebo (n = 434). Graft angiography was obtained a mean of 10.8 days after the operation. Electrocardiograms, cardiac enzymes, and blood loss and replacement were evaluated. RESULTS: In 796 assessable patients, aprotinin reduced thoracic drainage volume by 43% (P < .0001) and requirement for red blood cell administration by 49% (P < .0001). Among 703 patients with assessable saphenous vein grafts, occlusions occurred in 15.4% of aprotinin-treated patients and 10.9% of patients receiving placebo (P = .03). After we had adjusted for risk factors associated with vein graft occlusion, the aprotinin versus placebo risk ratio decreased from 1.7 to 1.05 (90% confidence interval, 0.6 to 1.8). These factors included female gender, lack of prior aspirin therapy, small and poor distal vessel quality, and possibly use of aprotinin-treated blood as excised vein perfusate. At United States sites, patients had characteristics more favorable for graft patency, and occlusions occurred in 9.4% of the aprotinin group and 9.5% of the placebo group (P = .72). At Danish and Israeli sites, where patients had more adverse characteristics, occlusions occurred in 23.0% of aprotinin- and 12.4% of placebo-treated patients (P = .01). Aprotinin did not affect the occurrence of myocardial infarction (aprotinin: 2.9%; placebo: 3.8%) or mortality (aprotinin: 1.4%; placebo: 1.6%). CONCLUSIONS: In this study, the probability of early vein graft occlusion was increased by aprotinin, but this outcome was promoted by multiple risk factors for graft occlusion.

Adjustment to residential placement in Alzheimer disease patients: does premorbid personality matter?

AIM: To evaluate the influence of premorbid personality on adaptation to placement in a long-term care facility. SUBJECTS: Twenty-eight persons with probable Alzheimer disease (AD) residing in an academically affiliated nursing home for 6-9 months. METHODS: Premorbid personality was described retrospectively by two informants for each resident using the revised NEO Personality Inventory (NEO-PI-R). Standardized tests and rating scales were used on admission to the facility to assess cognition, mood state, physical dependency and general health. Nurses rated each AD resident's social behaviour, participation in activities and quality of sleep. RESULTS: Poorer adjustment was associated with more severe dementia but better physical health. None of the NEO-PI-R domain scores predicted adjustment. CONCLUSIONS: Contrary to popular belief, premorbid personality is relatively inconsequential for an AD patient's adaptation to a long-term care facility.

Access to information about famous individuals in Alzheimer's disease.

Alzheimer's disease (AD) patients and normal adults were tested in two complementary recognition tasks. On each trial of the faces task, participants matched the photograph of a famous individual to one of four names. On each tial of the names task, participants matched the name of a famous individual to one of four photographs. The AD patients made enough consistent errors across the two tasks to suggest an impairment in the storage of information about the individuals. In addition, they made enough inconsistent errors to suggest a generalized retrieval deficit. The AD patients performed as well on the faces taslk as on the names task, providing no evidence of a specialized deficit in the retrieval of lexical information.

Perseverations during paired-associate learning in Huntington's disease.

Verbal (word) and nonverbal (design) paired-associate tasks were administered to Huntington's disease (HD) patients and healthy control subjects. An AB-AC paradigm, in which the cue stimuli were paired with different responses on the learning (e.g., BED-REST) and test trials (e.g., BED-SHEET), was used. It was hypothesized that HD patients would continue to respond with AB associations on the AC trials. The results were contrary to expectations: Patients showed impaired learning of both verbal and nonverbal associations but did not display a perseverative response style, even when the associative strength between word pairs was manipulated to elicit perseverations. Patients made more nonperseverative than perseverative errors in all conditions, an error pattern similar to that of control subjects. HD patients did not demonstrate increased susceptibility to proactive interference on these associative learning tasks.

Mitral valve repair combined with aortic valve replacement.

BACKGROUND AND AIMS OF THE STUDY: Combined aortic and mitral valve replacement continues to result in significant morbidity and mortality. Although mitral repair has improved the results of mitral valve surgery, its influence on combined aortic valve replacement has not been assessed. METHODS: We reviewed 38 consecutive patients who underwent aortic valve replacement (AVR) and mitral repair (MR) between 1985 and 1995. The average age was 57 years; 20 were men and 18 women. Nineteen patients were considered high risk: six had previous cardiac surgery, three were on chronic dialysis, two required emergency surgery for low output syndrome, one had a chronic tracheotomy for chronic lung disease, and seven had left ventricular ejection fraction < 30%. MR consisted of ring application alone in 28 patients, chordal shortening in nine, posterior leaflet transfer in six and posterior leaflet resection in four. AVR was accomplished with 21 bioprostheses, 14 mechanical and three allograft valves. The mean (+/-SD) cross-clamp time was 133 +/- 41 min. Additional procedures included coronary bypass in six patients and tricuspid procedures in three. RESULTS: There were no operative deaths. Six patients died between 4 and 73 months postoperatively. Patient survival was 75% five and 67% 10 years after surgery. The causes of death were heart failure (two cases), and respiratory failure, drug overdose, electrolyte imbalance and unknown (one each). Logistic risk analysis was significant for females and rheumatic valve disease, bacterial endocarditis, and degenerated valve patients. During follow up there were no valve failures or endocarditis, but three embolic episodes occurred without permanent sequel. CONCLUSIONS: With increased surgical expertise, improved myocardial protection of MR combined with AVR offers excellent short- and long-term results, optimal chordal preservation, no valve failure and no endocarditis; it is the ideal choice where anti-coagulation is contraindicated. The prolonged cross-clamp time was well tolerated.

Aprotinin for primary coronary artery bypass grafting: a multicenter trial of three dose regimens.

BACKGROUND: High-dose aprotinin reduces transfusion requirements in patients undergoing coronary artery bypass grafting, but the safety and effectiveness of smaller doses is unclear. Furthermore, patient selection criteria for optimal use of the drug are not well defined. METHODS: Seven hundred and four first-time coronary artery bypass grafting patients were randomized to receive one of three doses of aprotinin (high, low, and pump-prime-only) or placebo. The patients were stratified as to risk of excessive bleeding. RESULTS: All three aprotinin doses were highly effective in reducing bleeding and transfusion requirements. Consistent efficacy was not, however, demonstrated in the subgroup of patients at low risk for bleeding. There were no differences in mortality or the incidences of renal failure, strokes, or definite myocardial infarctions between the groups, although the pump-prime-only dose was associated with a small increase in definite, probable, or possible myocardial infarctions (p = 0.045). CONCLUSIONS: Low-dose and pump-prime-only aprotinin regimens provide reductions in bleeding and transfusion requirements that are similar to those of high-dose regimens. Although safe, aprotinin is not routinely indicated for the first-time coronary artery bypass grafting patient who is at low risk for postoperative bleeding. The pump-prime-only dose is not currently recommended because of a possible association with more frequent myocardial infarctions.

Item priming and skill learning in amnesia.

This study employed a semantic decision-making task to examine both item priming and skill learning in amnesia, which traditionally have been demonstrated with separate tasks. Fourteen amnesic patients of mixed etiologies and 14 normal control subjects judged whether words represented animate or inanimate objects. One list was presented repeatedly on four continuous blocks of trials, and a new list was presented on the fifth block. For both groups, decision times decreased significantly from Block 1 to Block 5 (indicating skill acquisition) and increased significantly from Block 4 to Block 5 (indicating item-specific learning). The amnesic patients demonstrated a normal rate of skill learning, but a reduced magnitude of item priming. As expected, the amnesics had significantly impaired explicit memory of the implicitly learned items, as measured by recognition accuracy. The results suggest that both implicit and explicit learning of individual items is impaired in amnesia, despite normal semantic skill learning.

Nonsteroidal anti-inflammatory drugs in Alzheimer's disease.

We reviewed the records of 210 patients in the Johns Hopkins Alzheimer's Disease Research Center to evaluate the role of nonsteroidal anti-inflammatory drugs (NSAIDs) on clinical features and progression of the disease. We compared patients taking NSAIDs or aspirin on a daily basis (N = 32) to non-NSAID patients (N = 177) on clinical, cognitive, and psychiatric measures. The NSAID group had a significantly shorter duration of illness at study entry. Even after controlling for this difference, the NSAID group performed better on the Mini-Mental State Examination, Boston Naming Test, and the delayed condition of the Benton Visual Retention Test. Furthermore, analysis of longitudinal changes over 1 year revealed less decline among NSAID patients than among non-NSAID patients on measures of verbal fluency, spatial recognition, and orientation. These findings support other recent studies suggesting that NSAIDs may serve a protective role in Alzheimer's disease.

Using a computer model to explore impairments of acquisition processes following ingestion of diazepam.

Hypotheses about the information processes impaired in diazepam-induced amnesia were tested by fitting the output from a computer simulation of list learning to observed serial position curves and to overt rehearsal protocols. Twenty-four subjects received an average weight-relative dosage of 0.18 mg/kg oral diazepam; 24 subjects received placebo. Immediate free recall of 16-word lists was examined at 2- and 8-s presentation times. Subjects receiving diazepam recalled significantly fewer words than placebo subjects (diazepam = 6.77 +/- 2.39 words; placebo = 9.29 +/- 1.42 words); their memory impairment was greater at the 8-s than 2-s presentation time. Tests of nonlinear regression models based on computer simulations of list learning performance were consistent with the hypothesis that diazepam reduces rehearsal capacity and disrupts the formation or utilization of contextual and inter-item associations. Among these causes of diazepam-induced amnesia, the disruption of contextual associations appears most important. The results further suggest that quantitative modeling of memory data may complement traditional methods of inferring relationships between brain processes and cognitive dysfunction in amnesic states.

Selective dissociations of sedation and amnesia following ingestion of diazepam.

Forty-eight healthy volunteers received 0.2 mg/kg oral diazepam or a placebo in a double-blind manner. The effect of the drug on memory was assessed by the free recall of unrelated word lists, and arousal was assessed by subjective ratings of drowsiness, multiple trials of a digit cancellation task, and the rate at which subjects rehearsed aloud items from the word lists. As expected, diazepam, depressed both memory functioning and all three measures of arousal. However, within the diazepam group, rehearsal rate was the only arousal measure that correlated with performance on the recall task. When looking at change scores, or the degree to which performance deteriorated from baseline to the diazepam condition, digit cancellation reduction was the only arousal measure that correlated with recall deterioration. Analyses also revealed that the three arousal measures did not correlate with each other. Results support the view that the arousal/attentional system is composed of partially independent subsystems with varying relationships to memory functioning.

A comparison of in vitro cellular responses to mechanical and electrical stimulation.

In the last several decades, enormous interest has been generated toward understanding the cell as it is controlled by its external physical environment. The purpose of this study was to determine the effects of well-defined applied mechanical stress and time-varying electric fields on the cellular synthesis of connective tissue macromolecules. Chondrocytes harvested by trypsin digestion of 15-day-old chick embryo sternae were randomly dispersed and cultured on elastin membranes in a humidified atmosphere with 10 per cent CO2 and 90 per cent air. Following five days of growth in F12 media and 5 per cent fetal calf serum, the membranes underwent either 1) a 10 per cent cyclic mechanical stretch or 2) 60 Hz A.C. electrical stimulation with current densities of 1 to 1,000 nA/mm2 or 3) control without stimulation, each for an eight-hour period. C14-hydroxyproline incorporation into collagen, and H2 35 SO4 incorporation into glycosaminoglycans (GAGs) were measured by liquid scintillation techniques. Scanning and transmission electron microscopy analysis of control and stimulated cells demonstrated discernable differences. Both mechanically and electrically stimulated chondrocytes showed a two- to three-fold increase in GAG synthesis and a general depression in protein and collagen synthesis over controls. The general similarity in response to both mechanical and electrical stress suggests common processes by which they modulate cellular synthesis of cartilage connective tissue proteins.