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PubMedDate not supplied

Predictors of 1-year treatment outcome in bulimia nervosa.

We examined predictors of outcome 1 year after completion of a randomized clinical trial assessing the additive efficacy of two forms of exposure with response prevention to a core of cognitive-behavioral therapy (CBT) for bulimia nervosa (BN). One hundred one women who met DSM-III-R criteria for BN, and who completed the clinical trial, were available for follow-up at 1 year. Predictor variables were assessed prospectively and partitioned temporally to reflect lifetime history (including personality), pretreatment clinical status, and posttreatment clinical status. Outcome was based on the frequency of binging and purging in the 3 months before assessment based on carefully constructed lifechart interviews. A series of stepwise logistic regressions were performed to determine independent predictors of 1-year outcome while controlling for treatment received. Demographic variables were unrelated to treatment outcome. A history of obesity was predictive of poor outcome, whereas a history of alcohol dependence decreased the odds of poor outcome. High self-directedness on the Temperament and Character Inventory (TCI) predicted favorable outcome at 1 year, whereas personality disorder symptoms were not predictive. Pretreatment global functioning, bulimia scores on the Eating Disorders Inventory (EDI), and the presence of major depression predicted poor outcome. Posttreatment binging, food restriction, and urges to binge on a cue reactivity assessment predicted poor outcome at 1 year. The character trait of self-directedness is a strong predictor of good outcome for CBT, and methods to enhance this trait may be worthy of investigation. Low global functioning and the presence of major depression at presentation may require additional treatment than focused CBT for BN. Our results argue for treatment goals that include abstinence from binging and restricting and decreases in urges to binge in response to high-risk cues.

Adolescent↗

PubMed2002

Bacillus subtilis functional genomics: global characterization of the stringent response by proteome and transcriptome analysis.

The stringent response in Bacillus subtilis was characterized by using proteome and transcriptome approaches. Comparison of protein synthesis patterns of wild-type and relA mutant cells cultivated under conditions which provoke the stringent response revealed significant differences. According to their altered synthesis patterns in response to DL-norvaline, proteins were assigned to four distinct classes: (i) negative stringent control, i.e., strongly decreased protein synthesis in the wild type but not in the relA mutant (e.g., r-proteins); (ii) positive stringent control, i.e., induction of protein synthesis in the wild type only (e.g., YvyD and LeuD); (iii) proteins that were induced independently of RelA (e.g., YjcI); and (iv) proteins downregulated independently of RelA (e.g., glycolytic enzymes). Transcriptome studies based on DNA macroarray techniques were used to complement the proteome data, resulting in comparable induction and repression patterns of almost all corresponding genes. However, a comparison of both approaches revealed that only a subset of RelA-dependent genes or proteins was detectable by proteomics, demonstrating that the transcriptome approach allows a more comprehensive global gene expression profile analysis. The present study presents the first comprehensive description of the stringent response of a bacterial species and an almost complete map of protein-encoding genes affected by (p)ppGpp. The negative stringent control concerns reactions typical of growth and reproduction (ribosome synthesis, DNA synthesis, cell wall synthesis, etc.). Negatively controlled unknown y-genes may also code for proteins with a specific function during growth and reproduction (e.g., YlaG). On the other hand, many genes are induced in a RelA-dependent manner, including genes coding for already-known and as-yet-unknown proteins. A passive model is preferred to explain this positive control relying on the redistribution of the RNA polymerase under the influence of (p)ppGpp.

Bacillus subtilis↗

PubMed1997

Baseline quality of life of patients with advanced prostate cancer. European Organization for Research and Treatment of Cancer (EORTC), Genito-Urinary Tract Cancer Cooperative Group (GUT-CCG)

Quality of life (QoL) is now commonly studied in prostate cancer. However, little is known about the appropriateness of the various QoL instruments in this group of patients. The purpose of this work was to study the baseline QoL assessment of patients with prostate cancer who were randomised into three EORTC phase III studies. The three trials included locoregional prostate cancer patients, poor prognosis metastatic patients and hormone resistance patients, respectively. In the three trials, patients were asked to complete a questionnaire assessing their physical and psychosocial functioning and their symptom levels. These questionnaires included questions from the EORTC QLQ-C30 (version 1): the physical functioning, role functioning, global health/QoL scales and a single pain item. The psychometric properties of the scales were assessed and an analysis was performed to investigate if differences existed in the scale scores between the three groups of patients, 638 baseline questionnaires were available for patients entered into the three trials. The Gutman coefficients of reproducibility and scalability were 0.94 and 0.71, respectively, for the physical functioning scale and 0.97 and 0.90, respectively, for the role functioning scale. The Cronbach's alpha reliability coefficients were 0.68, 0.48 and 0.90 for the physical functioning, role functioning and global health/QoL scales, respectively. The four scales were able to distinguish clearly between the patient populations under study. The physical functioning, role functioning, global health/QoL scales and the single pain item scale from the EORTC QLQ-C30 (version 1) are valid measures when used in the setting of prostate cancer.

Activities of Daily Living↗

PubMed1997

Divergence and conservation of the partitioning and global regulation functions in the central control region of the IncP plasmids RK2 and R751.

The central control region (Ctl) of IncP plasmids is associated with two phenotypes: the coordinate expression of replication and transfer genes; and the ability to increase the segregational stability of a low-copy number test plasmid. This region of the IncP beta plasmid R751 shows significant sequence divergence from the IncP alpha plasmid RK2 sequence, and two genes, korF and korG, present in the IncP alpha region are missing in the IncP beta Ctl. In other respects the organization of the Ctl is basically the same. Although the two key global regulatory genes korA and korB are highly conserved, studies on their ability to repress transcription from a variety of IncP alpha and IncP beta plasmid promoters suggest differences in operator recognition by KorA and synergy with other repressors. The products of kfrA, upf54.8 and upf54.4 genes are conserved; KfrA shows least conservation and, while retaining the ability to act as a transcriptional repressor, appears to have completely different DNA-binding specificity. The genes required for the plasmid segregational stabilization (partitioning) phenotype--incC, korB and the korB operator OB3--are conserved and contribute to a more efficient plasmid stabilization than the IncP alpha equivalents. This may indicate that the Ctl plays an especially important role in partitioning of IncP beta plasmids, since they lack the second stability region (parlmrs) found in IncP alpha plasmids.

Bacterial Proteins↗

PubMed2002

Non-cognitive benefits of galantamine (Reminyl) treatment in vascular dementia.

Vascular dementia (VaD) is a condition that involves deterioration in cognitive and non-cognitive areas. Although cognitive impairment is the defining symptom evaluated during clinical trials, changes in non-cognitive areas such as behavior, global functioning and activities of daily living are assessed because they assist in determining quality of life and overall well-being. Therapy has focused traditionally on preventing and controlling risk factors, as no approved treatments are currently available for these patients. Acetylcholinesterase inhibitors (AChEIs), the treatment of choice in patients with Alzheimer's disease (AD), are a potential treatment option for patients with VaD. Galantamine, an AChEI with nicotinic receptor modulation, has demonstrated clinically relevant benefits (cognition, global functioning, functional ability, behavior) in patients with either AD with cerebrovascular disease (AD with CVD) or probable VaD in a 6-month, randomized, double-blind, placebo-controlled study.

Activities of Daily Living↗

PubMed2001

Effectiveness of a Mobile Outreach and Crisis Services unit in reducing psychiatric symptoms in a population of homeless persons with severe mental illness.

The purpose of this study was to use a time-lag design to evaluate the effectiveness of a Mobile Outreach and Crisis Services unit in remitting psychiatric symptomatology, improving global functioning, and decreasing homelessness in a population of homeless, severely mentally ill residing in a mid-sized urban center. Using a time-lag study design, two groups of subjects--25 individuals before receiving services (control group) and 25 individuals after receiving services (experimental group)--were contrasted across outcome measures. The results indicate that a MOCS unit utilizing a Program for Assertive Community Treatment mode was effective in significantly decreasing psychiatric symptomatology, reducing homelessness, and increasing global functioning. If carefully implemented and interpreted, a time-lag design may be a means of providing valuable feedback and information in a timely manner.

Community-Institutional Relations↗

PubMed1999

Quantification of 99Tcm-sestamibi and 123I-BMIPP uptake for predicting functional outcome in chronically ischaemic dysfunctional myocardium.

Little is known about the usefulness of free fatty acid scintigraphy for assessing viability in chronic ischaemic heart disease. To investigate this, we quantified the uptake of 99Tcm-sestamibi and 123I-BMIPP at rest twice within 6 months in 20 patients with chronic ischaemic left ventricular dysfunction and infarction. Four patterns of the relative distribution of both tracers were observed and classified as normal, mismatched, matched and scar. The proportion of the left ventricular surface corresponding to each pattern was expressed as the percentage of the total surface using a polar map. Between the two studies, the patients either underwent revascularization or were treated conservatively. The quantitative results were compared with those of dobutamine stress echocardiography (DSE) in arterial territories with resting contractile dysfunction and correlated with the evolution of regional and global function at follow-up. At baseline, 25 arterial territories were analysed. Using sestamibi, on average one-third of their surface was considered to be normally perfused. No clear association was found between the percent normally perfused surface and the DSE findings. Adding BMIPP and using a value of > 7% of the arterial surface with BMIPP lower than sestamibi (mismatch) as the cut-off for the significance of viability, 14 of 18 mismatched regions were considered viable by DSE, and six of seven with < 7% mismatched surface or matching were not. Fifteen patients were viable, of whom 13 were revascularized (16 territories). At follow-up, global function improved in 11 of the 15 viable patients, all in the revascularized group. Regional improvement was noted in 11 of 16 revascularized territories, and was associated with a significant increase in sestamibi and BMIPP uptake and in the percent normally perfused myocardial surface. In the five patients without significant viability, no functional deterioration or changes in the quantitative parameters were observed during treatment. The results suggest that quantitative analysis of the uptake of sestamibi and BMIPP is a reliable method to objectively assess the presence of myocardial viability in chronic ischaemic heart disease and to predict functional improvement after revascularization.

Aged↗

PubMed1987

Improvement of myocardial function after global hypoxia by protection of the inner mitochondrial membrane.

In the present study the hypothesis is tested that hypoxia causes morphological damage to the inner mitochondrial membrane and that this damage can be reversed by modification of the reoxygenated perfusate. Using the working rat heart model, hearts in group I (n = 40) were subjected to a 30 min normothermic, normoxic phase and a 90 min hypoxic phase, followed by 60 min reoxygenation. Hearts in group II (n = 32) were also subjected to a 30 min normoxic and a 90 min hypoxic phase. However, after 30 min of reoxygenation 1.5 mmol/l 2-mercaptopropionylglycine (MPG) was injected in the reoxygenated solution in order to test its ability to improve mitochondrial function. Mitochondrial function was assessed by measuring oxygen uptake (ST3), ST4, respiratory control index (RCI), ADP/O and oxidative phosphorylation rate (OPR). In addition mechanical function (heart rate, aortic and coronary flow, cardiac output, stroke volume) was monitored along with ultrastructural parameters. 90 min of hypoxia caused a deterioration of all parameters with persistent impairment in hemodynamic, morphologic and biochemical functions after 60 min of reoxygenation (group I). The role of the ATP-synthetases in the pathogenesis of oxygen-paradox is discussed. In contrast, the MPG-enriched reoxygenated solution (group II) improved hemodynamics, ultrastructure and mitochondrial function significantly (alpha = 0.05). It is concluded from these data that the ATP-synthetases are damaged during oxygen-deficiency and that MPG may be a useful drug for protecting the inner mitochondrial membranes during reoxygenation.

Adenosine Diphosphate↗

PubMed1993

Quantitative planar rest-redistribution 201Tl imaging in detection of myocardial viability and prediction of improvement in left ventricular function after coronary bypass surgery in patients with severely depressed left ventricular function.

BACKGROUND: Although many patients with multivessel coronary artery disease (CAD) and severely depressed left ventricular (LV) function will benefit from coronary artery bypass graft surgery (CABG), surgeons may be reluctant to perform CABG on these patients without evidence of myocardial viability in regions of severe asynergy. We hypothesized that quantitative planar rest-redistribution 201Tl imaging would identify viable myocardium and predict improved regional and global function after revascularization in patients with depressed LV function and CAD. METHODS AND RESULTS: Twenty-one patients (mean LV ejection fraction, 0.27 +/- 0.05) were studied. Regional and global LV functions were evaluated before and 8 weeks after CABG with radionuclide ventriculography. Segments were prospectively classified as showing normal, mildly reduced, or severely reduced viability on the basis of quantitative analysis of defect severity and redistribution on planar resting 201Tl imaging. By 201Tl criteria, 90% of hypokinetic segments were classified with normal or mildly reduced viability. Among akinetic or dyskinetic segments, 20% had normal 201Tl uptake, 53% had mildly reduced viability, and only 27% had severely reduced viability. 201Tl viability criteria identified segments that improved function after CABG. Sixty-two percent of severely asynergic segments with normal viability and 54% with mildly reduced viability improved function after surgery, but only 23% with severely reduced viability improved function (p = 0.002). When only adequately revascularized segments were considered, the predictive value of a positive preoperative viability scan for functional improvement was 73%. The greatest improvement in global LV function after CABG occurred in patients with the greatest number of asynergic segments classified as viable before surgery (p < 0.01). In 10 patients with more than seven viable, asynergic segments, mean LV ejection fraction increased significantly after CABG (0.29 +/- 0.07 to 0.41 +/- 0.11, p = 0.002). In 11 patients with seven or fewer viable, asynergic segments, mean LV ejection fraction remained unchanged after revascularization (0.27 +/- 0.05 to 0.30 +/- 0.08, p = NS). CONCLUSIONS: In patients with CAD and severely depressed LV function, preoperative quantitative planar rest-redistribution. 201Tl imaging identifies viability in many asynergic myocardial segments, and these segments frequently improve function after CABG. The presence of numerous asynergic but viable myocardial segments before surgery correlated significantly with improvement in global LV function after bypass surgery.

Aged↗

PubMed1997

Frequent attender profiles: different clinical subgroups among frequent attender patients in primary care.

Psychiatric and physical morbidity among frequently attending patients in primary care is high. However, very few efforts have been made to sort out the complex patterns of problems these patients have. We developed a clinical grouping of these patients. Our sample consisted of 67 frequent attenders. The measures included physical and psychiatric illnesses, presenting symptoms, sociodemographic data, psychosocial situation, level of distress, global functioning, experienced life satisfaction, illness attribution, and current psychiatric treatment. We identified five groups with different profiles: (1) patients with entirely physical illnesses; (2) patients with clear psychiatric illnesses; (3) crisis patients; (4) chronically somatizing patients; and (5) patients with multiple problems. The grouping was based on multidimensional operational criteria. The majority in all groups attended for solely physical illnesses or symptoms suggesting different forms of somatization. Only a few patients were undergoing any psychiatric treatment. Differences between groups were found regarding sociodemographic factors, physical illnesses, global functioning, and satisfaction.

Adolescent↗

PubMed2000

Evaluation of transmyocardial laser revascularization by following objective parameters of perfusion and ventricular function.

BACKGROUND: Does transmyocardial laser revascularization (TMLR), a new surgical technique for treating patients with otherwise intractable angina pectoris, improve myocardial perfusion, metabolism, and, consequently, function? METHODS: Patients referred for TMLR, alone or with coronary artery bypass grafting (CABG), were preoperatively evaluated clinically and by treadmill stress testing, echocardiography, ventriculography, radionuclide assessment of perfusion and metabolism, and hemodynamic assessment. Intraoperatively it was decided that some patients only required CABG. Follow-up evaluations were repeated after 6 (n = 40) and 12 months (n = 23) and compared with preoperative values. RESULTS: CABG only was performed in 35 cases, TMLR + CABG in 17, TMLR only in 45. 1-year mortality was 11% in the TMLR, zero in the TMLR + CABG, and 11% in the CABG groups. In all groups a significantly improved CCS angina- and NYHA class was observed immediately after operation and after 6 and 12 months. In all study groups treadmill tolerance (p<0.05) improved, but regional and global function, perfusion at rest, and metabolism were not significantly changed at 6 and 12-months follow-ups. Perfusion studies under stress demonstrated an improvement only in the CABG group after 12 months (p<0.05), whereas in both TMLR groups the lasered ischemic segments remained unchanged. CONCLUSIONS: TMLR significantly improves long-term clinical status and treadmill stress tolerance, but appears to have little if any effect upon regional and global function, perfusion, and metabolism.

Aged↗

PubMed1996

Compliance therapy in psychotic patients: randomised controlled trial.

OBJECTIVE: To determine whether compliance therapy, a cognitive-behavioural intervention, could improve compliance with treatment and hence social adjustment in acutely psychotic inpatients, and if so, whether the effect persisted six months later. DESIGN: Randomised controlled trial of compliance therapy and non-specific counselling, each comprising 4-6 sessions lasting 10-60 minutes. SETTING: Acute psychiatric admissions ward serving an inner London catchment area. SUBJECTS: 47 patients with psychosis. MAIN OUTCOME MEASURES: Informant and observer reported measure of compliance; observer assessed global functioning after intervention and three and six months later; self-rated attitudes to drug treatment after the intervention and one month later; symptom scores after intervention and six months later. RESULTS: 25 patients received compliance therapy and showed significantly greater improvements in their attitudes to drug treatment and in their insight into illness and compliance with treatment compared with the control group. These gains persisted for six months. The intervention group was 5.2 times more likely than the control group to reach a criterion level of compliance (95% confidence interval 1.5 to 18.3). Global functioning showed a tendency to improve more in the intervention group after a delay (odds ratio 3.0 (0.8 to 11.5) to reach the criterion level at six months). Four subjects given compliance therapy and six in the control group were readmitted during follow up (odds ratio 2.0 (0.48 to 8.2)). CONCLUSIONS: Compliance therapy is a pragmatic method for improving compliance with drug treatment in psychotic inpatients and its gains persist for at least six months. Overall functioning may also be enhanced.

Acute Disease↗

PubMed2001

Severely mentally ill substance abusers: an 18-month follow-up study.

BACKGROUND: The aims of this study were to investigate initial characteristics and improvement after 18 months in patients with comorbidity of severe mental illness and substance dependence. These patients took part in a multicentre study aimed at improving co-operation between psychiatric health care units and social services. METHODS: A total of 358 patients, 66% men, were included. There were four diagnostic subgroups: psychosis 29%, depression 17%, borderline personality disorder 23%, and other diagnoses of equal severity 31%. Initially and at follow-up the following measurements were used: global functioning axis V DSM-III-R (GAF), seven areas of Addiction Severity Index (ASI) and psychological symptoms (SCL-90). The outcome of substance use during the past 6 months was estimated by the Clinical Rating Scale (CRS). RESULTS: Most patients were single (77%) and few (10%) had income from employment. Many (61%) had made suicide attempts, and 52% had somatic diseases before entering this project. After 18 months, 14 patients (3.9%) had died, and 288 patients (84%) could be interviewed. There were significant improvements in all but one ASI area (employment), in psychological symptoms and in global functioning. There was a positive correlation between the reductions in severity of alcohol abuse, drug abuse, psychiatric symptoms, relationships (ASI) and psychological symptoms. Forty-eight percent of patients with mainly alcohol-related problems, and 57% of those with mainly drug-related problems were either "abstinent" or using drugs "without impairment" (CRS) after 18 months. Improvement did not differ between psychiatric subgroups. CONCLUSION: These patients have weak social integration. Alcohol dependence was the most common substance use disorder. In most areas investigated, patients had improved. No substance abuse was found in half of the patients at follow-up.

Adult↗

PubMed2003

Increased frequency of rolandic spikes in ADHD children.

PURPOSE: Some children with rolandic epilepsy have associated neuropsychiatric deficits resembling symptoms of attention deficit-hyperactivity disorder (ADHD), the most common neurobehavioral disorder of childhood. The clinical overlap between both syndromes has received relatively little attention. The study examines the frequency of rolandic spikes in nonepileptic children with ADHD and compares it with a historic control group of 3,726 normal school-aged children. ADHD patients with and without discharges are compared regarding age at admission, sex, global functioning, and distribution of ADHD subtypes. METHODS: The EEGs of 483 ADHD outpatients between 2 and 16 years meeting diagnostic criteria for ADHD according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) were evaluated prospectively. If rolandic spikes were present, separate sleep EEGs were performed to exclude a bioelectrical status epilepticus during slow-wave sleep. RESULTS: Rolandic spikes were detected in the EEGs of 27 children (5.6%; 22 boys and five girls). Seizure rate during follow-up tended to be larger in children with rolandic spikes. No significant differences were found between ADHD patients with and without spikes regarding sex and global functioning. ADHD children with rolandic spikes came to our attention significantly earlier than did children without discharges and tended to exhibit more hyperactive-impulsive symptoms, evidenced in a larger proportion of the diagnosis of ADHD combined type than ADHD inattentive type. CONCLUSIONS: The frequency of rolandic spikes in children with ADHD is significantly higher than expected from epidemiologic studies. The question arises how ADHD symptoms are related to rolandic spikes in this ADHD subgroup. Possibly rolandic discharges or underlying, not fully understood mechanisms of epileptogenesis decrease the vulnerability threshold, advance the onset, or aggravate the course of ADHD.

Action Potentials↗

PubMedDate not supplied

The effects of donepezil in Alzheimer's disease - results from a multinational trial.

Donepezil has been shown to be well tolerated and to improve cognition and global function in patients with mild to moderately severe Alzheimer's disease (AD). The current trial was undertaken to investigate further the efficacy and safety of donepezil, in a multinational setting, in patients with mild to moderately severe AD. This 30-week, placebo-controlled, parallel-group study consisted of a 24-week, double-blind treatment phase followed by a 6-week, single-blind, placebo washout. Eight hundred and eighteen patients with mild to moderately severe AD were randomly allocated to treatment with single, daily doses of 5 or 10 mg donepezil, or placebo. The two primary efficacy measures were: a cognitive performance test, the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and a global evaluation, the Clinician's Interview-Based Impression of Change with caregiver input (CIBIC plus). Secondary outcome measures included the Sum of the Boxes of the Clinical Dementia Rating Scale (CDR-SB), a modified Interview for Deterioration in Daily living activities in Dementia (IDDD) and a patient rated quality of life assessment. Statistically significant improvements in cognitive and global function were observed, as evaluated by ADAS-cog and CIBIC plus, respectively, in both the 5 and 10 mg/day donepezil groups, compared with placebo. Treatment-associated changes were also observed in functional skills, as shown by improved scores on the CDR-SB and the complex-tasks component of the IDDD. A dose-response effect was evident, with the 10 mg/day donepezil group demonstrating greater benefits in all outcome measures than the 5 mg/day group. Donepezil was well tolerated by this patient population and did not produce any clinically significant laboratory test abnormalities. The results of this study confirm that donepezil is effective and well tolerated in treating the symptoms of mild to moderately severe AD.

Aged↗

PubMed2001

A new global test for the evaluation of the activated factor II-antithrombin system.

We developed a new simple test to evaluate the global function of the activated factor II-antithrombin system. The new test measures the clotting time of plasma samples after the addition of a reagent containing a snake venom (Echis carinatus) that can activate prothrombin, with (Ta) and without (To) heparin. The prolongation of clotting times (Ta - To) is directly related to the function of the activated factor II-antithrombin system. The presence of quantitative or functional defects of the natural inhibitors (antithrombin and heparin co-factor II), or high levels of factor II and/or fibrinogen, can trigger a resistance to the inhibition of activated factor II. This new test was used to examine 134 thrombophilic patients as well as 157 normal subjects as controls. The results obtained confirm that the presence of abnormalities relating to the activated factor II-antithrombin system causes a resistance to activated factor II inhibition even if a significant number of patients was found to have a resistance that could not be accounted for. Since the new test can be easily performed automatically and has a good inter- and intra-assay variation coefficient (CV < 4%) it is useful for evaluating the global function of the activated factor II-antithrombin system in screening thrombophilic patients, alongside the tests already known and used to diagnose these patients.

Antithrombins↗

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↗

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↗