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PubMed1998

Metrifonate treatment of the cognitive deficits of Alzheimer's disease. Metrifonate Study Group.

The efficacy and safety of metrifonate, an acetylcholinesterase inhibitor, was evaluated clinically in patients diagnosed with mild to moderate Alzheimer's disease (AD). This was a prospective, 30-week, multicenter, double-blind, randomized, parallel group, dose-finding study, which included a 2-week screening period, a 12-week treatment period, and follow-up visits at 8 and 16 weeks post-treatment. Patients received placebo or metrifonate once daily. Metrifonate-treated patients received a loading dose of 0.5 mg/kg (25 to 45 mg), 0.9 mg/kg (45 to 80 mg), or 2.0 mg/kg (100 to 180 mg) for 2 weeks, followed by a maintenance dose of 0.2 mg/kg (10 to 20 mg), 0.3 mg/kg (15 to 25 mg), or 0.65 mg/kg (30 to 60 mg) for 10 weeks. Four hundred eighty patients were enrolled. Percentages of patients completing double-blind treatment were 96% in the placebo group and 89 to 94% in the metrifonate group. Metrifonate significantly improved cognitive ability, as assessed by the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and enhanced global function, as assessed the Clinicians's Interview-Based Impression of Change with Caregiver Input (CIBIC-Plus). At 3 months, in the intent-to-treat patients, the treatment difference for the change in ADAS-Cog score in favor of metrifonate was 2.94 points (95% CI, 1.61 to 4.27; p = 0.0001). These patients also exhibited a 0.35-point improvement on the CIBIC-Plus relative to the placebo patients (95% CI, 0.15 to 0.54; p = 0.0007). Patients receiving lower drug doses had scores intermediate to those of the placebo and the 0.65 mg/kg metrifonate groups on both performance scales. The drug was well tolerated; side effects were predominantly gastrointestinal in nature, and no hepatic toxicity was observed. Therefore, in this study, metrifonate safely improved the cognitive deficits and benefited the global function of AD patients.

Aged↗
PubMed2006

Transcriptional profiling of the cell cycle checkpoint gene krüppel-like factor 4 reveals a global inhibitory function in macromolecular biosynthesis.

Krüppel-like factor 4 (KLF4; also known as gut-enriched Krüppel-like factor or GKLF) is known to exhibit checkpoint function during the G1/S and G2/M transitions of the cell cycle. The mechanism by which KLF4 exerts these effects is not fully established. Here we investigated the expression profile of KLF4 in an inducible system over a time course of 24 h. Using oligonucleotide microarrays, we determined that the fold changes relative to control in expression levels of KLF4 exhibited a time-dependent increase from 3- to 20-fold between 4 and 24 h following KLF4 induction. During this period and among a group of 473 cell cycle regulatory genes examined, 96 were positively correlated and 86 were negatively correlated to KLF4's expression profile. Examples of upregulated cell cycle genes include those encoding tumor suppressors such as MCC and FHIT, and cell cycle inhibitors such as CHES1 and CHEK1. Examples of downregulated genes include those that promote the cell cycle including several cyclins and those required for DNA replication. Unexpectedly, several groups of genes involved in macromolecular synthesis, including protein biosynthesis, transcription, and cholesterol biosynthesis, were also significantly inhibited by KLF4. Thus, KLF4 exerts a global inhibitory effect on macromolecular biosynthesis that is beyond its established role as a cell cycle inhibitor.

Cell Cycle↗
PubMed1987

[How to evaluate recirculation effect on brain function after global ischemia--broad spectral EEG analysis by Fourier method].

EEG alterations after 5 or 10 minutes of global ischemia were investigated for 6 hours of postischemic period in 18 adult cats, together with biophysiological parameters such as cerebral blood flow, intracranial pressure, systemic blood pressure, heart rate, and blood gases. Our EEG analytical system is composed of high fidelity pre-amplifier, AA 6 MK II (Medelec Limited, England) and signal processor 7T 08 (NEC-SanEi, Japan). It is qualified to analyze frequencies up to 20 kHz within 3 dB cut-off. Particular features of our EEG analytical method are focused on Fourier analysis about broad frequency bands, frequency and amplitude spectra to be expressed on bi-logarithmic graph and direct EEG recordings from various structures of the brain. On the basis of fluctuation theory following 3 types were divided; Type f which corresponds to 1/f fluctuation, Type L which corresponds to Lorentzian fluctuation, Type f+L which is the sum of Type f and L. The distribution of these types in the central nervous system corresponds with cortical structures, spinal cord and brain stem respectively. In conclusion, there was a good correlation between EEG and blood flow in the motor cortex. The functional reversibility after ischemia was different according to the types. Type f structures, namely the motor cortex, hippocampus and amygdala were vulnerable and Type f+L structures namely ventrolateral nucleus of the thalamus and midbrain reticular formation tended to recover or stay in preservation.

Animals↗
PubMedDate not supplied

[Diagnostic, symptomatic and sanitary assessment of schizophrenic patients in Liege psychiatric institutions].

This study was designed to provide a diagnostic, symptomatologic and sanitary assessment of schizophrenic patients in the network of institutions of the Plate-Forme Psychiatrique Liégeoise (Liège, Belgium). The diagnosis of schizophrenia was based on the DSM IV. Demographic, social and global functioning (GAF scale) data were collected from the Résumé Psychiatrique Minimum (RPM) , a clinical summary which has been imposed for each psychiatric hospital stay by the Belgian Ministry of Public Health. Symptoms components were derived from the Psychosis Evaluation tool for Commom Use by Caregivers (PECC). In the 44 participating institutions, 793 cases of schizophrenia were reported (533 men and 260 women) with a mean age of 46.1 14.4 years. The study confirmed the predominance of men in schizophrenia (67%) but revealed that women were about 6 years higher than men. PECC symptoms were studied in a random sample of 184 patients extracted from the 793 initial patients and analysed with respect to age, sex and type of care (full-time or part-time hospitalization, ambulatory care). Negative, cognitive and total PECC scores did not vary with sex but were positively correlated with age. Hospitalized patients were significantly older than the others. The cognitive deficit was significantly higher in hospitalized patients than in other patients, while the perception of the disease tended to be more apparent in ambulatory than in hospitalized patients. Data were also related to social information and global functioning. The GAF scores increased with age but were comparable in men and women. Moreover, GAF scores were significantly lower in catatonic type schizophrenia patients than in others.

Adult↗
PubMed1994

Influence of residual perfusion within the infarct zone on the natural history of left ventricular dysfunction after acute myocardial infarction: a myocardial contrast echocardiographic study.

OBJECTIVES: This study used myocardial contrast echocardiography to investigate the extent of residual perfusion within the infarct zone in a select group of patients with recently reperfused myocardial infarction and evaluated its influence on the ultimate infarct size. BACKGROUND: Limited information is available on the status of myocardial perfusion within postischemic dysfunctional segments at predischarge and on its influence on late regional and global functional recovery. METHODS: Twenty patients with acute myocardial infarction were selected for the study. Patients met the following inclusion criteria: 1) single-vessel coronary artery disease; 2) patency of infarct-related artery with persistent postischemic dysfunctional segments at predischarge; 3) stable clinical condition up to 6 months after hospital discharge. All selected patients underwent coronary angiography and myocardial contrast echocardiography before hospital discharge and repeated the echocardiographic examination 6 months later. Patients were grouped according to the pattern of contrast enhancement in predischarge dysfunctional segments. RESULTS: In nine patients (group I), the length of segments showing abnormal contraction coincided with that of the contrast defect segments. In the remaining 11 patients (group II), postischemic dysfunctional segments were partly or completely reperfused. There was no difference between the two groups in asynergic segment length at predischarge (7.3 +/- 2.5 vs. 7.2 +/- 4.3 cm, p = NS). At follow-up study, asynergic segment length was significantly reduced in group II patients, whereas no changes were observed in group I patients (from 7.2 +/- 4.3 to 4.7 +/- 3.7 cm, p < 0.005; and from 7.3 +/- 2.5 to 7.5 +/- 2.9 cm, p = NS, respectively). CONCLUSIONS: Among patients with a predischarge patent infarct-related artery, further improvement in regional and global function may be expected during follow-up when residual perfusion in the infarct zone is present.

Adult↗
PubMed1986

Local myocardial and global ventricular function compared during positive inotropic medication.

The assessment of the pharmacological efficiency of cardiotonic drugs interferes with the complex force generation within the spatially netted myocardial meshwork. By multifocal local force and distance measurements we distinguished "afterloaded" from "unloading" force types, which essentially differ in their transient behaviour during changes in ventricular shape. Histologically we found the "afterloaded" force type in oblique fibre populations whereas the "unloading" force curve is generated in surface parallel fibres. Amrinon reduces pre- and afterload, thus inducing ventricular shrinkage. The resulting rearrangement of the intramural force pattern modifies the transmission of fibre tension to ventricular ejection in a way that contractility indices, derived from left ventricular pressure, become inapplicable. However, direct intracoronary drug injection, monitored by segmental force and distance measurements within the irrigated myocardial area, characterizes Amrinon as a potent positive inotropic drug.

Amrinone↗
PubMed1991

Client typology based on functioning level assessments: utility for service planning and monitoring.

Cluster analysis was used to develop a six-group typology based on level of functioning data from 2,447 clients with serious mental illness served by the Michigan public mental health system. The groups are described in terms of level of functioning in 16 domains, global functioning, diagnosis, demographic characteristics and services used. A group of older, poor functioning clients with high health needs was identified. A second group of highly dysfunctional clients with few health needs was also found. Two groups of young adult "chronic" clients were found: one with extensive substance abuse problems and one with moderate substance abuse problems and extreme levels of suicidal and aggressive behavior. Two groups of relatively good functioning clients were also identified: one with some problems in many areas and a second with functional problems in a number of life areas and pronounced symptoms of depression and demoralization. The results point to the utility of cluster analysis as a mechanism to organize and identify patterns within the rich array of information provided by multidimensional level of functioning assessments. The uses of empirically derived client types in planning and monitoring mental health services are discussed.

Catchment Area, Health↗
PubMed2000

Can dimercaptosuccinic acid renal scintigraphy be used to assess global renal function?

Use of dimercaptosuccinic acid (DMSA) has been proposed for the assessment of both relative and absolute renal function. Our aim was to test whether the renal absolute DMSA uptake (ADU) can reflect the absolute renal function from a theoretical point of view. A simple model was used to compute the ADU in the case of injury to one kidney. It was found that the assumption that ADU correctly reflects the absolute renal function may lead to a more than 50% overestimation of the function of both the normal and the impaired kidney. The later the measurement is made and the more impaired is the kidney, the more important is the error. Although DMSA can reliably quantify the relative renal function, it should not be used to assess absolute renal function lest major overestimation should occur.

Humans↗
PubMed1976

Methylprednisolone treatment in acute myocardial infarction. Effect on regional and global myocardial function.

The effects of methylprednisolong treatment on acute myocardial ischemia were studied in nine closed chest dogs. After 1 hour of proximal occlusion of the left anterior descending coronary artery, an intravenous bolus injection (50 mg/kg body weight) of methylprednisolone was administered and its effects studied during an additional 2 hours of occlusion. After 2 hours of treatment the following significant mean alterations from levels after 1 hour of occlusion were noted: an increase of 16.7% in heart rate and decreases of 23% in left ventricular end-diastolic pressure, 32% in stroke volume, 14% in cardiac output and 37% in stroke work. Peak systolic pressure, maximal rate of rise of left ventricular pressure (dP/dt), left ventricular end-diastolic volume, systemic vascular resistance and coronary sinus blood flow changed less than 10%. Ejection fraction and regional cardiac wall motion were not improved. Metabolic dysfunction of the coronary-occluded myocardium, revealed by regional lactate as well as potassium derangements, persisted throughout the 2 hour treatment period. Comparison of these results with equivalent data from an untreated series of nine dogs with 3 hours of occlusion demonstrated no improvement in the treated series. Methylprednistone failed to restore regional cardiac metabolic and mechanical function, and treatment was associated with a further rise in S-T segment elevations. Administration of methylprednisolone after 1 hour of proximal left anterior descending coronary occlusion apparently does not reverse cardiac dysfunction in the first 2 hours of treatment.

Acute Disease↗
PubMed1986

Theophylline improves global cardiac function and reduces dyspnea in chronic obstructive lung disease.

Theophylline has been utilized widely as a bronchodilator, but only in recent years have its positive cardiovascular effects been recognized in patients with chronic obstructive pulmonary disease. After intravenous administration of aminophylline, pulmonary artery pressures and pulmonary vascular resistance are reduced, and both right and left ventricular ejection fraction are increased. Similar short- and long-term enhancement of biventricular performance is produced by orally administered long-acting theophylline. Possible mechanisms for this theophylline-induced improvement in right and left ventricular systolic pump performance include enhanced ventricular inotropy and reduced ventricular afterload. A recent study has established that orally administered theophylline also reduces dyspnea in patients with chronic obstructive pulmonary disease. Accordingly, in patients with chronic obstructive pulmonary disease theophylline may be useful for reducing pulmonary artery pressure and pulmonary vascular resistance, treating right or left heart failure, reducing dyspnea, and partially reversing airway obstruction.

Dyspnea↗
PubMed1984

A microcomputer-based package for determination of regional and global cardiac function and coronary hemodynamics.

A multichannel data acquisition package for reduction of systemic and coronary hemodynamic data that utilizes a personal microcomputer is described. The system provides a printout of heart rate, maximal rate of left ventricular pressure development (+dP/dt), maximal rate of ventricular relaxation (-dP/dt), absolute and normalized myocardial segment lengths, the degree of shortening of the segment over the cardiac cycle, systolic, diastolic, and mean coronary blood flow velocities, left ventricular systolic and end diastolic pressures, and systolic, diastolic, and mean aortic blood pressure from six channels of input data. Obtained values are precisely linked to the cardiac cycle. To illustrate the output of this system, data obtained by reading strip-chart records are compared to microcomputer-derived values in conscious, instrumented dogs.

Animals↗
PubMed2004

Sharing time on the fly.

The investigation of circadian clock function in Drosophila has progressed from the identification of clock genes to the analysis of timing mechanisms in the cells and tissues where these genes are expressed. As the biological context for investigating circadian clock systems is expanded, new features of molecular timing mechanisms are becoming apparent. Examples come first from studies on peripheral clocks, which perform local, tissue-specific functions as well as global functions that relate to the control of individual behavior, and second from the evaluation of social influences on circadian rhythms. The identification of inter-organismal components of the circadian system in Drosophila suggests new perspectives as the progression continues from the systems level to the social level and onwards to the level of ecosystems.

Animals↗
PubMed1997

Affect recognition in schizophrenia: a function of global impairment or a specific cognitive deficit.

To investigate cognitive variables related to affect recognition in schizophrenia, 63 subjects with DSM-III-R diagnoses of schizophrenia or schizoaffective disorder were administered a test battery which included the Bell-Lysaker Emotion Recognition Task (BLERT), Wisconsin Card Sorting Test (WCST), Wechsler Memory (WMS-R) and Adult Intelligence Scales (WAIS-R), Hopkins Verbal Learning Test, Gorham's Proverbs, and Continuous Performance Task (CPT). Coefficients revealed a moderate relationship between emotion recognition and WCST and CPT but no significant relationship with other test variables. Multiple regression analysis demonstrated that approximately one-third of the variance in BLERT scores could be explained by cognitive variables including the Digit Symbol Subtest, CPT, and Hopkins Verbal Learning Test. Other analyses demonstrated that subjects with moderate to severe affect recognition impairment had more perseverative errors, had fewer complete categories on the WCST and had more errors on the CPT. However, there were no significant differences on global measures of impairment such as WAIS-R IQs and Digit Symbol Substitution Test. The discussion focuses on deficits in affect recognition as a distinct feature which contributes to the heterogeneity of the disorder.

Adult↗
PubMed1999

Wall motion of noninfarcted myocardium. Relationship to regional and global systolic function and to early and late left ventricular dilation.

We studied the wall motion of the noninfarcted area and its role in left ventricular remodeling. The study group consisted of 43 patients with a first Q-wave acute myocardial infarction and single-vessel disease. Cardiac catheterization was performed at the first week, and was repeated six months later. Left ventricular volumes, wall motion at the infarcted and noninfarcted area, ejection fraction and infarction-related artery status were quantified. Hyperkinesia was only found at the first week in 22% of cases, and at the sixth month in 26% of cases. Wall motion at the noninfarcted area correlated with wall motion at the infarcted area (one week: r=0.53 p<0.0001; six months: r=0.52 p=0.01), ejection fraction (one week: r=0.69 p<0.0001; six months: r=0.56 p=0.006), end-diastolic volume (one week: r=-0.48 p=0.002; six months: r=-0.48 p=0.02) and end-systolic volume (one week: r=-0.70 p<0.0001; six months: r=-0.64 p=0.001). The improvement of the noninfarcted area (from the first week to the sixth month) was only related to basal (one week) wall motion in this area (r=-0.58 p=0.003). We conclude that after an intermediate-large infarction, most patients exhibit a normal or hypokinetic noninfarcted area. Patients with a more depressed infarcted area show poorer contractility at the noninfarcted area. area exhibit greater progressive improvement.

Adult↗
PubMed1998

Elderly recipients of home nursing services: pain, disability and functional competence.

Despite increasing evidence that pain is a problem with which many in their later years must contend, little is known about the experience of community-dwelling seniors who require the assistance of home nursing services to remain independent and functional in their homes. This study investigated the prevalence and experience of pain among seniors who were recipients of home nursing services. The study was guided by the World Health Organization Classification of Impairment, Disability and Handicap. Face to face interviews were conducted with 66 individuals who reported whether they were often troubled by pain and/or had experienced pain of a noteworthy nature within the 2 weeks prior to the interview. In addition, they responded to standardized questions about their pain experience and their levels of disability and functional competence. Findings revealed that although three-quarters of respondents reported pain, there was no association between pain and measures of disability. Findings, however, revealed an association between pain and measures of functional competence, more specifically, global function, level of depressive symptomatology, sleep impairment and satisfaction with life. Implications for nursing include the need for a heightened awareness of the prevalence of pain in community-dwelling older adults and the development of assessment and intervention strategies that support their quality of life.

Activities of Daily Living↗