[An experimental study of evaluating regional left ventricular systolic function and global left ventricular pumping function by 2-dimension echocardiography].
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BACKGROUND: Cognitive impairment contributes substantially to disability in bipolar disorder (BD), but effective pharmacologic options remain limited. This trial evaluated whether adjunctive memantine improves global cognition and executive function in BD. METHODS: In this double-blind, placebo-controlled randomized trial, patients with bipolar I disorder (B1D) receiving lithium and olanzapine were assigned to memantine or placebo. Memantine was titrated to 20 mg/day over 6 weeks. Cognitive outcomes were assessed at baseline, week 6, and week 18. Global cognition was measured with the Neurocognitive Assessment Battery (NuCog), and executive function with the Frontal Assessment Battery (FAB). Data were analyzed using generalized estimating equations and Bonferroni-adjusted post-hoc tests. RESULTS: Sixty-three participants were randomized (memantine, n = 31; placebo, n = 32), and all completed follow-up. Groups were comparable at baseline for demographic and clinical variables and for most cognitive measures. Both groups improved over time (P < 0.001), but improvement was greater with memantine for global cognition at week 6 (MD = 9.32; 95% CI, 4.84-13.81; P < 0.001) and week 18 (MD = 12.69; 95% CI, 8.67-16.71; P < 0.001). FAB total scores favored memantine at week 18 (MD = 2.68; 95% CI, 1.76-3.61; P < 0.001), but not at week 6. Domain analyses showed significant benefits for NuCog attention, visuoconstructional ability, memory, and executive function, and for several FAB subscales by week 18. CONCLUSIONS: Adjunctive memantine improved global cognition and, over longer follow-up, executive function in BD. These findings support NMDA receptor modulation as a potential strategy for cognitive dysfunction in BD.
Patients with coronary artery disease often have impaired left ventricular diastolic filling despite normal global systolic function. The influence of regional systolic asynchrony on diastolic function was assessed by radionuclide angiography in 60 patients with coronary artery disease and normal ejection fraction at rest: group 1 (n = 30) with normal wall motion at rest and group 2 (n = 30) with abnormal wall motion. Data were compared with those obtained from 19 normal volunteers. Age, heart rate, ejection fraction and echocardiographic end-diastolic dimension did not differ among the three groups. Peak filling rate in group 1 and group 2 was similar (2.5 +/- 0.5 and 2.3 +/- 0.6 end-diastolic counts/s, respectively) and significantly lower than that in the normal subjects (2.8 +/- 0.7 end-diastolic counts/s; p less than 0.01 vs. group 2, p less than 0.05 vs group 1). Time to peak filling rate was prolonged in group 2 (184 +/- 27 ms) compared with that in normal subjects (162 +/- 19 ms; p less than 0.01) and group 1 (172 +/- 15 ms; p less than 0.05). Left ventricular end-diastolic pressure was significantly higher in group 2 than in group 1 (14 +/- 7 vs. 10 +/- 5 mm Hg, respectively; p less than 0.05). Asynchrony was assessed by sector analysis of the radionuclide left ventricular region of interest. Diastolic asynchrony was similar in the two patient groups (30 +/- 23 ms in group 2, 26 +/- 16 ms in group 1) and was higher in both groups than in the normal subjects (16 +/- 8 ms; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Trauma is a risk factor for early-onset (EOP) and adult-onset (AOP) psychosis and is also associated with other psychiatric diagnoses and poorer fputcomes in the general population. We examined (1) whether trauma effects are specific to psychosis and (2) whether these effects differ between EOP and AOP.Linear regression models evaluated trauma exposure in two samples (EOP: 647 cases, 694 controls; AOP: 162 cases, 230 controls) as a function of psychotic and nonpsychotic psychiatric diagnosis (NPD) status. Parallel models assessed associations between trauma and symptom severity, global functioning, and cognition. Relative to individuals without psychiatric disorders, participants with psychosis and comorbid NPDs reported the greatest trauma exposure (EOP: β = 0.95; AOP: β = 1.1), followed by those with psychosis only (EOP: β = 0.67; AOP: β = 0.41) and NPDs only (EOP: β = 0.47; AOP: β = 0.36). Greater numbers of NPDs were associated with higher trauma exposure regardless of psychosis status (EOP: β = 0.15; AOP: β = 0.24). Trauma was associated with greater symptom severity (EOP: β = 0.13; AOP: β = 0.14) and poorer global functioning (EOP: β = -0.21; AOP: β = -0.13), but not cognition. No psychosis-by-trauma interactions were observed.Psychosis-specific effects were limited to greater trauma exposure, while trauma-related impacts on outcomes were similar across diagnostic groups. Findings were consistent across EOP and AOP. Results highlight the need for trauma-informed care in psychiatry given broad effects that influence disease course and prognosis.
Perfusion and ventilation lung scintigraphy are indicated: (1) for evaluating regional perfusion and ventilation, (2) for establishing a ratio between ventilation and perfusion in different areas of the lung, (3) when chest surgery is planned (especially for mapping out the extent of resection), (4) when surgery of the upper abdomen is to be performed, and (5) when global function studies are compromised. Regional ventilation and perfusion studies are invaluable in the diagnosis of pulmonary thromboembolism in which a perfusion defect is accompanied by well-preserved ventilation in the underperfused area. Regional function tests are indicated for evaluating the distribution of ventilation and pulmonary circulation in practically any chronic pulmonary disease, especially when global function studies, such as spirometry, show significant decreases.
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.
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The ejection fraction as determined by gated blood pool studies was compared with the ejection fraction as evaluated by the following conventional methods: 1) biplane cineangiography employing the Simpson rule. Correlation was r = 0.805 (n = 25); 2) the same patients using the area-length method (r = 0.88, n = 25); 3) monoplane cineangiography using the method of Greene et al. (5) (r = 0.86, n = 35). In 20 patients the maximal contraction velocity as evaluated by radionuclide ventriculography was compared with the mean systolic ejection rate. The observed correlation was weak (r = 0.62, n = 20); however, it should be noted that the radionuclide method determines the maximum contraction velocity whereas cinceangiography measures an average value over the whole systole.
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In 25 patients with ischaemic heart disease the effect of nitroglycerin [NTG] on segmental and global function of the left ventricle was assessed by means of left ventricular cineangiography. In 14 patients a segmental disturbance of contraction at rest was found; in six of them the function inproved after NTG. After NTG, the left ventricular diastolic volume, end-diastolic pressure, and systolic blood pressure decreased, the heart rate increased. The global left ventricular function did not significantly change. In patients with ischaemic heart disease NTG helps to differentiate reversible and irreversible disturbances of left ventricular contraction.
The effect of postextrasystolic potentiation [PESP] on left ventricular [LV] function was assessed by means of left ventricular cineangiography in 26 patients with ischaemic heart disease. Ventricular extrasystoles were induced by a catheter inserted into the LV during injection of the contrast agent. The values of parameters of segmental and global function of LV, found in potentiated and nonpotentiated sinus contractions, were compared. Segmental disturbances present at rest in 13 patients improved or disappeared after extrasystole in 8 patients. Improvements in contraction also took place in segments with normal resting contraction. Global LV function improved significantly; an improvement was observed even without an increase in the LV end-diastolic volume in the postextrasystolic beat. The advantages and limitations of the method for preoperative estimation of the effect of intended myocardial revascularization on the LV function are discussed.
To determine the sequence of changes in segmental myocardial function, regional lactate metabolism and global left ventricular function induced by mild regional ischemia, blood flow in the left anterior descending coronary artery of 10 dogs was reduced by 10 percent decrements with use of a screw clamp. At each level of flow, segmental mechanical function and regional metabolism were assessed, the former with use of a mercury-in-Silastic length gauge and the latter with transmyocardial lactate balance measurements obtained with sampling from the anterior interventricular vein. Coronary arterial flow at the onset of regional lactate production was 48 +/- 4 percent (mean +/- standard error of the mean) of the control value. The onset of segmental mechanical dysfunction coincided with the onset of lactate production. Epicardial S-T segment abnormalities over the ischemic zone usually could not be detected until coronary flow was further reduced. After the onset of regional ischemia there was a linear correlation between coronary arterial flow and regional lactate production. At the onset of mild regional ischemia, defined as the onset of regional lactate production, no significant or directionally consistent changes were noted in standard measurements of global left ventricular performance, including heart rate, mean aortic pressure, left ventricular end-diastolic pressure, cardiac output, stroke volume, stroke work and peak positive dP/dt (maximal rate of rise of pressure). However, peak negative dP/dt (maximal rate of pressure decrease) decreased from 99 +/- 2 to 89 +/- 3 percent of the control value (P less than 0.0005) coincident with the onset of ischemia. It is hypothesized that dyssynchronous wall motion in the ischemic zone during isometric relaxation accounts for this decrease in peak negative dP/dt.
PURPOSE: Evaluation of the clinical effects of captopril addition to the conventional therapy of functional class II and III (NYHA) congestive heart failure (CHF). METHODS: One hundred and fifteen patients with CHF, 46 (40%) class II and 69 (60%) class III, on conventional treatment (digitalis and diuretic) were the subject of this study. The age ranged from 22 to 75 years (mean 56.6 +/- 11); 67 were male and 66 were caucasians. The etiologies of the heart failure were: hypertensive heart disease 47 (40.9%), ischemic heart disease 27 (23.5%), Chagas cardiomyopathy 20 (17.4%), idiopathic cardiomyopathy 15 (13.0%), and other causes 6 (5.2%). Diuretic and digitalis were maintained in the same dosage during all the treatment. Captopril therapy was started with 6.25 mg b.i.d. or t.i.d., and the dosage was increased gradually to 25 mg b.i.d. or t.i.d. The duration of the study was 12 weeks. Clinical visits occurred every four weeks and laboratory tests were performed in the beginning and at the end of the study. RESULTS: The dosage of captopril ranged from 12.5 to 75 mg (mean 28.5 +/- 13.1 mg/day). The addition of captopril to the conventional therapy of CHF was associated with significant reduction (p < 0.01) of heart rate, systolic and diastolic blood pressure. In the end of the study 13 patients (11.3%) were in functional class III, 50 (43.5%) in class II and 52 (45.2%) in class I. Globally, functional class was improved in 98 (85.2%) patients and remained unchanged in 17 (14.8%) (p < 0.01). The side effects (dizziness, cough, hypotension and headache) were moderate and uncommon and did not need interruption of the treatment. CONCLUSION: The addition of captopril to the conventional therapy of class II and III CHF was associated with significant improvement of functional class and with good tolerability.
Shotgun metagenomic sequencing can determine both the taxonomic and functional content of microbiomes. However, functional classification for metagenomic reads remains highly challenging as protein mapping tools require substantial computational resources and yield ambiguous classifications when short reads map to homologous proteins originating from different bacteria. Here we introduce kMermaid for the purpose of uniquely mapping bacterial short reads to taxa-agnostic clusters of homologous proteins, which can then be used for downstream analysis tasks such as read quantification and pathway or global functional analysis. Using a nested hash map containing amino acid k-mer profiles as a model for protein assignment, kMermaid achieves the sensitivity of popular existing protein mapping tools while remaining highly resource efficient. We evaluate kMermaid on simulated data and data from human fecal samples as well as demonstrate the utility of kMermaid for classifying reads originating from new, unseen proteins. kMermaid allows for highly accurate, unambiguous and ultrafast metagenomic read assignment into protein clusters, with a fixed memory usage, and can easily be employed on a typical computer.
PURPOSE: Because of concerns about late toxicities of treatment among infants diagnosed with acute lymphoblastic leukemia (ALL), and especially the effects of cranial radiation therapy (CRT), we compared the functional and neuropsychologic status of 26 long-term survivors of ALL who were diagnosed in the first 24 months of life versus 26 children who were treated previously for Wilms' tumor. PATIENTS AND METHODS: Of the children with ALL, CNS prophylaxis included no CRT in six, 18 Gy CRT in five, 20 Gy CRT in seven, and 24 Gy CRT in five. Three additional children experienced CNS relapse and received total CRT doses of 24, 40, and 44 Gy. All children received neuropsychologic testing; children with ALL also participated in diagnostic imaging studies. RESULTS: As a group, the children who were treated for ALL did not differ significantly from those who were treated for Wilms' tumor on objective measures of global functional status. However, children treated for ALL had a significantly lower mean intelligence quotient (IQ) (87 v 96), poorer performance on four of six measures of visual and auditory memory, lower achievement with regard to arithmetic skills, and a greater frequency of special educational intervention than those who were treated for Wilms' tumor. IQ and auditory memory performance in the ALL group was correlated inversely with time since the completion of therapy and total CRT dose. CONCLUSIONS: These results reinforce the contemporary trend of prophylactic CRT omission in very young children except for those who are at risk for CNS relapse. For infants and very young children who require CRT, evidence is presented that supports the approach for the delay of CRT until the child is older.
Twenty newly diagnosed, untreated hypertensive men (diastolic blood pressure greater than 105 mm Hg) and 20 normotensive controls were given a neuropsychological battery, including tests of generalized, more global functions (eg, reaction time and full-scale IQ) and of specific functions (eg, language and visual-spatial abilities) sensitive to focal damage. Tests of specific abilities yielded no differences between the two groups. In contrast, tests of general neuropsychological functioning revealed a deficit among hypertensives, who were significantly slower on the reaction time test and had a shorter span for digits in forward order. Results suggest that arterial hypertension is associated with impairment of vigilance and attention span. Future research will determine whether this impairment is associated with the diffuse pathological changes seen in the brain of hypertensive subjects, or with a more "functional" change (eg, reduced cerebral blood flow).
Atrio--ventricular conduction and its modifications induced by six Beta-adrenergic blocking agents have been investigated in the dog. Premature atrial stimuli (St2) were applied at variable intervals following regular stimuli (St1) ensuring atrial pacing; atrial (AERP), nodoventricular (NERP) and global (GERP) effective refractory periods as well as global functional refractory period (GFRP) were determined before and after administration of each of the six drugs. When Beta-blockade was produced with d,1-propranolol which hwas membrane stabilizing effects (MSE) but no intrinsic sympathomimetic activity (ISA) or with sotalol, which has neither MSE nor ISA, all parameters were significantly increased. When Beta-blockade was achieved with pindolol or practolol, which have only a poor Beta-adrenolytic potency and no ISA. Alprenolol showed intermediate effects. Thus, it appears that Beta-blockade and not MSE, is responsible for the onset of A-V conduction impairment but that ISA, probably through a metabolic mechanism, affords protection against this impairment. On the other hand, measurement of ventricular effective refractory period (VERP) has shown that at the Purkinje-free junction, it is MSE which is mainly involved in conduction impairment.